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For the tactical shooting technique, see Flaccid paralysis (shooting).
"Flaccid" redirects here. For the states of the half-erect penis or clitoris tissues, see Tumescence.
Flaccid paralysis
Pronunciation
* /ˈflæksɪd pəˈræləsɪs/
SpecialtyNeurology
Flaccid paralysis is a neurological condition characterized by weakness or paralysis and reduced muscle tone without other obvious cause (e.g., trauma).[1] This abnormal condition may be caused by disease or by trauma affecting the nerves associated with the involved muscles. For example, if the somatic nerves to a skeletal muscle are severed, then the muscle will exhibit flaccid paralysis. When muscles enter this state, they become limp and cannot contract. This condition can become fatal if it affects the respiratory muscles, posing the threat of suffocation.[2]
## Contents
* 1 Causes
* 1.1 Polio and other viruses
* 1.2 Botulism
* 1.3 Curare
* 1.4 Other
* 2 References
* 3 Further reading
* 4 External links
## Causes[edit]
### Polio and other viruses[edit]
See also: Acute flaccid myelitis
The term acute flaccid paralysis (AFP) is often used to describe an instance with a sudden onset, as might be found with polio.
AFP is the most common sign of acute polio, and used for surveillance during polio outbreaks. AFP is also associated with a number of other pathogenic agents including enteroviruses other than polio, echoviruses, West Nile virus, and adenoviruses, among others.[3]
### Botulism[edit]
The Clostridium botulinum bacteria are the cause of botulism. Vegetative cells of C. botulinum may be ingested. Introduction of the bacteria may also occur via endospores in a wound. When the bacteria are in vivo, they induce flaccid paralysis. This happens because C. botulinum produces a toxin which blocks the release of acetylcholine. Botulism toxin blocks the exocytosis of presynaptic vesicles containing acetylcholine (ACh).[2] When this occurs, the muscles are unable to contract.[4] Other symptoms associated with infection from this neurotoxin include double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness. Botulism prevents muscle contraction by blocking the release of acetylcholine, thereby halting postsynaptic activity of the neuromuscular junction. If its effects reach the respiratory muscles, then it can lead to respiratory failure, leading to death.[5]
### Curare[edit]
Curare is a plant poison derived from - among other species - Chondrodendron tomentosum and various species belonging to the genus Strychnos, which are native to the rainforests of South America. Certain peoples indigenous to the region - notably the Macusi \- crush and cook the roots and stems of these and certain other plants and then mix the resulting decoction with various other plant poisons and animal venoms to create a syrupy liquid in which to dip their arrow heads and the tips of their blowgun darts. Curare has also been used medicinally by South Americans to treat madness, dropsy, edema, fever, kidney stones, and bruises.[6] Curare acts as a neuromuscular blocking agent which induces flaccid paralysis. This poison binds to the acetylcholine (ACh) receptors on the muscle, blocking them from binding to ACh. As a result, ACh accumulates within the neuromuscular junction, but since ACh cannot bind to the receptors on the muscle, the muscle cannot be stimulated. This poison must enter the bloodstream for it to work. If curare affects the respiratory muscles, then its effects can become life-threatening, placing the victim at risk for suffocation.[2]
### Other[edit]
Flaccid paralysis can be associated with a lower motor neuron lesion. This is in contrast to an upper motor neuron lesion, which often presents with spasticity, although early on this may present with flaccid paralysis.[citation needed]
Included in AFP's list are poliomyelitis (polio), transverse myelitis, Guillain–Barré syndrome, enteroviral encephalopathy,[7] traumatic neuritis, Reye's syndrome, etc.
An AFP surveillance programme is conducted to increase case yield of poliomyelitis. This includes collection of two stool samples within fourteen days of onset of paralysis and identification of virus, and control of the outbreak and strengthening immunization in that area.[citation needed]
Historical records from the 1950s, modern CDC reports, and recent analysis of patterns in India suggest that flaccid paralysis may be caused in some cases by oral polio vaccinations.[8][9][10]
Venomous snakes that contain neurotoxic venom such as kraits, mambas, and cobras can also cause complete flaccid paralysis.[11] Some chemical warfare nerve agents such as VX can also cause complete flaccid paralysis.[12]
## References[edit]
1. ^ Alberta Government Health and Wellness (2005) Acute Flaccid Paralysis Public Health Notifiable Disease Management Guidelines.
2. ^ a b c Saladin, Kenneth S. Anatomy & Physiology: The Unity of Form and Function. McGraw-Hill. 6th Edition. 2012.
3. ^ Kelly H, Brussen KA, Lawrence A, Elliot E, Pearn J, Thorley B (June 2006). "Polioviruses and other enteroviruses isolated from faecal samples of patients with acute flaccid paralysis in Australia, 1996-2004". Journal of Paediatrics and Child Health. 42 (6): 370–6. doi:10.1111/j.1440-1754.2006.00875.x. PMID 16737480.
4. ^ "Disease Listing, Botulism, General Information - CDC Bacterial, Mycotic Diseases".
5. ^ "flaccid paralysis - definition of flaccid paralysis in the Medical dictionary - by the Free Online Medical Dictionary, Thesaurus and Encyclopedia". Medical-dictionary.thefreedictionary.com. Retrieved 2014-02-26.
6. ^ "Curare - Chondrodendron tomentosum". Blueplanetbiomes.org. Retrieved 2014-02-26.
7. ^ Idris M, Elahi M, Arif A (Jan–Mar 2007). "Guillain Barre syndrome: the leading cause of acute flaccid paralysis in Hazara division". Journal of Ayub Medical College, Abbottabad. 19 (1): 26–8. PMID 17867475.
8. ^ "Public Health Dispatch: Acute Flaccid Paralysis Associated with Circulating Vaccine-Derived Poliovirus --- Philippines, 2001". MMWR. Morbidity and Mortality Weekly Report. 50 (40): 874–5. October 12, 2001.
9. ^ Dissolving Illusions: Diseases. Vaccines and the Forgotten History. Suzanne Humphries MD and Roman Bystrianyk. 2013.
10. ^ Vashisht, Neetu; Puliyel, Jacob; Sreenivas, Vishnubhatla (February 2015). "Trends in Nonpolio Acute Flaccid Paralysis Incidence in India 2000 to 2013". Pediatrics. 135 (Supplement 1): S16–S17. doi:10.1542/peds.2014-3330DD.
11. ^ GJ Müller; H Modler; CA Wium; DJH Veale; C J Marks (October 2012). "Snake bite in southern Africa: diagnosis and management". Continuing Medical Education. 30 (10): 362–381. Retrieved 2 March 2015.
12. ^ Sidell, Frederick R. (1997). "Chapter 5: Nerve Agents" (PDF). Medical Aspects of Chemical and Biological Warfare. p. 144ff.
## Further reading[edit]
* "Progress towards poliomyelitis eradication, Nepal, 1996-1999". Relevé Épidémiologique Hebdomadaire. 74 (42): 349–53. October 1999. PMID 10895300.
* Centers for Disease Control Prevention (CDC) (September 2002). Centers for Disease Control and Prevention (CDC). "Acute flaccid paralysis syndrome associated with West Nile virus infection--Mississippi and Louisiana, July-August 2002". MMWR. Morbidity and Mortality Weekly Report. 51 (37): 825–8. PMID 12353741.
* Sejvar JJ, Leis AA, Stokic DS, Van Gerpen JA, Marfin AA, Webb R, Haddad MB, Tierney BC, Slavinski SA, Polk JL, Dostrow V, Winkelmann M, Petersen LR (July 2003). "Acute flaccid paralysis and West Nile virus infection". Emerging Infectious Diseases. 9 (7): 788–93. doi:10.3201/eid0907.030129. PMC 3023428. PMID 12890318.
* Saeed M, Zaidi SZ, Naeem A, Masroor M, Sharif S, Shaukat S, Angez M, Khan A (2007). "Epidemiology and clinical findings associated with enteroviral acute flaccid paralysis in Pakistan". BMC Infectious Diseases. 7: 6. doi:10.1186/1471-2334-7-6. PMC 1804272. PMID 17300736.
## External links[edit]
* WHO Programme for Immunization Preventable Diseases (IPD) A Collaboration between World Health Organization and Government of Nepal
Classification
D
* ICD-10: G81.0, G82.0, G82.3
* ICD-9-CM: 359.9
Look up flaccid in Wiktionary, the free dictionary.
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Flaccid paralysis | c0085620 | 3,600 | wikipedia | https://en.wikipedia.org/wiki/Flaccid_paralysis | 2021-01-18T18:53:04 | {"icd-9": ["359.9"], "icd-10": ["G82.0", "G82.3", "G81.0"], "wikidata": ["Q5456583"]} |
Human disease
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Find sources: "La Crosse encephalitis" – news · newspapers · books · scholar · JSTOR (September 2015) (Learn how and when to remove this template message)
La Crosse encephalitis
SpecialtyInfectious disease
La Crosse encephalitis is an encephalitis caused by an arbovirus (the La Crosse virus) which has a mosquito vector (Ochlerotatus triseriatus synonym Aedes triseriatus).[1]
La Crosse encephalitis virus (LACV) is one of a group of mosquito-transmitted viruses that can cause encephalitis, or inflammation of the brain. LAC encephalitis is rare; in the United States, about 80–100 LACV disease cases are reported each year, although it is believed to be under-reported due to minimal symptoms experienced by many of those affected.[2]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Prevention
* 4 Treatment
* 5 Epidemiology
* 6 Related conditions
* 7 References
* 8 External links
## Signs and symptoms[edit]
It takes 5 to 15 days after the bite of an infected mosquito to develop symptoms of LACV disease. Symptoms include nausea, headache, vomiting in milder cases and seizures, coma, paralysis and permanent brain damage in severe cases.
LAC encephalitis initially presents as a nonspecific summertime illness with fever, headache, nausea, vomiting and lethargy. Severe disease occurs most commonly in children under the age of 16 and is characterized by seizures, coma, paralysis, and a variety of neurological sequelae after recovery. Death from LAC encephalitis occurs in less than 1% of clinical cases. In many clinical settings, pediatric cases presenting with CNS involvement are routinely screened for herpes or enteroviral causes. Since there is no specific treatment for LAC encephalitis, physicians often do not request the tests required to specifically identify LAC virus, and the cases are reported as aseptic meningitis or viral encephalitis of unknown cause.
As with many infections, the very young, the very old and the immunocompromised are at a higher risk of developing severe symptoms.
## Cause[edit]
La Crosse orthobunyavirus
Virus classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Negarnaviricota
Class: Ellioviricetes
Order: Bunyavirales
Family: Peribunyaviridae
Genus: Orthobunyavirus
Species:
La Crosse orthobunyavirus
The La Crosse encephalitis virus is a type of arbovirus called a bunyavirus.[3] The Bunyavirales are mainly arboviruses.
Most cases of LAC encephalitis occur in children under 16 years of age. LAC virus is a zoonotic pathogen cycled between the daytime-biting treehole mosquito, Aedes triseriatus, and vertebrate amplifier hosts (chipmunks, tree squirrels) in deciduous forest habitats. The virus is maintained over the winter by transovarial transmission in mosquito eggs. If the female mosquito is infected, she may lay eggs that carry the virus, and the adults coming from those eggs may be able to transmit the virus to chipmunks and to humans.[citation needed]
Anyone bitten by a mosquito in an area where the virus is circulating can get infected with LACV. The risk is highest for people who live, work or recreate in woodland habitats, because of greater exposure to potentially infected mosquitoes.[citation needed]
## Prevention[edit]
People reduce the chance of getting infected with LACV by preventing mosquito bites. There is no vaccine or preventive drug.
Prevention measures against LACV include reducing exposure to mosquito bites. Use repellent such as DEET and picaridin, while spending time outside, especially at during the daytime - from dawn until dusk. Aedes triseriatus mosquitoes that transmit (LACV) are most active during the day. Wear long sleeves, pants and socks while outdoors. Ensure all screens are in good condition to prevent mosquitoes from entering your home. Aedes triseriatus prefer treeholes to lay eggs in. Also, remove stagnant water such as old tires, birdbaths, flower pots, and barrels.[4]
## Treatment[edit]
No specific therapy is available at present for La Crosse encephalitis, and management is limited to alleviating the symptoms and balancing fluids and electrolyte levels. Intravenous ribavirin is effective against La Crosse encephalitis virus in the laboratory, and several studies in patients with severe, brain biopsy confirmed, La Crosse encephalitis are ongoing.
In a trial with 15 children being infected with La Crosse viral encephalitis were treated at certain phases with ribavirin (RBV). RBV appeared to be safe at moderate doses. At escalated doses of RBV, adverse events occurred and then the trial was discontinued. Nonetheless, this was the largest study of antiviral treatment for La Crosse encephalitis.[5]
## Epidemiology[edit]
La Crosse encephalitis was discovered in 1965, after the virus was isolated from stored brain and spinal tissue of a child who died of an unknown infection in La Crosse, Wisconsin in 1960.[6] It occurs in the Appalachian and Midwestern regions of the United States. Recently there has been an increase of cases in the South East of the United States. An explanation to this may be that the mosquito Aedes albopictus is also an efficient vector of La Crosse virus. Aedes albopictus is a species that has entered the US and spread across the SE of the US and replaced Aedes aegypti in most areas (which is not an efficient vector of LAC).
Historically, most cases of LAC encephalitis occur in the upper Midwestern states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the mid-Atlantic (West Virginia, Virginia and North Carolina) and southeastern (Alabama and Mississippi) regions of the country. It has long been suspected that LAC encephalitis has a broader distribution and a higher incidence in the eastern United States, but is under-reported because the causal agent is often not specifically identified.
LAC encephalitis cases occur primarily from late spring through early fall, but in subtropical areas where the mosquito is found (e.g., the Gulf states), rare cases can occur in winter.
According to the CDC, between 2004 and 2013 there were 787 total cases of La Crosse encephalitis and 11 deaths in the U.S.[7]
Looking at the distribution of cases across the United States by state, between 2004 and 2013 the most cases of La Crosse encephalitis was in North Carolina. North Carolina had 184 total cases, followed by Ohio with 178 total cases.[8]
## Related conditions[edit]
Similar diseases that are spread by mosquitoes include: Western and Eastern equine encephalitis, Japanese encephalitis, Saint Louis encephalitis and West Nile virus.
## References[edit]
1. ^ McJunkin, J. E.; de los Reyes, E. C.; Irazuzta, J. E.; Caceres, M. J.; Khan, R. R.; Minnich, L. L.; Fu, K. D.; Lovett, G. D.; Tsai, T.; Thompson, A. (March 2001). "La Crosse Encephalitis in Children". The New England Journal of Medicine. 344 (11): 801–7. doi:10.1056/NEJM200103153441103. PMID 11248155.
2. ^ "Epidemiology & Geographic Distribution | la Crosse encephalitis | CDC". 2018-09-14.
3. ^ Center for Disease Control and Prevention (CDC) (January 2009). "Possible Congenital Infection with La Crosse Encephalitis Virus — West Virginia, 2006–2007". MMWR. Morbidity and Mortality Weekly Report. 58 (1): 4–7. PMID 19145220.
4. ^ "Prevention". Centers for Disease Control and Prevention. 11 April 2016. Retrieved 6 December 2016.
5. ^ McJunkin, JE (October 2011). "Safety and pharmacokinetics of ribavirin for the treatment of la crosse encephalitis". The Pediatric Infectious Disease Journal. 30 (10): 860–5. doi:10.1097/INF.0b013e31821c922c. PMID 21544005.
6. ^ Thompson, W.H.; Kalfayan, B.; Anslow, R.O. (1965). "Isolation of California encephalitis virus from a fatal human illness". Am. J. Epidemiol. 81 (2): 245–253. doi:10.1093/oxfordjournals.aje.a120512. PMID 14261030.
7. ^ "La Crosse virus disease cases and deaths reported to CDC by year and clinical presentation, 2004-2013" (PDF). Centers for Disease Control and Prevention. Retrieved 4 December 2016.
8. ^ "La Crosse virus disease cases reported to CDC by state, 2004–2013" (PDF). Centers for Disease Control and Prevention. Retrieved 8 December 2016.
## External links[edit]
Classification
D
* ICD-10: A83.5
* ICD-9-CM: 062.5
* MeSH: D004670
External resources
* Orphanet: 83483
* "La Crosse Encephalitis". CDC. 2018-05-03. Retrieved 2012-02-25.
* Directors of Health Promotion and Education Facts Sheet La Crosse Encephalitis
* Encephalitis Global Inc. Offering information and support to encephalitis survivors, caregivers and loved ones.
* v
* t
* e
Zoonotic viral diseases (A80–B34, 042–079)
Arthropod
-borne
Mosquito
-borne
Bunyavirales
* Arbovirus encephalitides: La Crosse encephalitis
* LACV
* Batai virus
* BATV
* Bwamba Fever
* BWAV
* California encephalitis
* CEV
* Jamestown Canyon encephalitis
* Tete virus
* Tahyna virus
* TAHV
* Viral hemorrhagic fevers: Rift Valley fever
* RVFV
* Bunyamwera fever
* BUNV
* Ngari virus
* NRIV
Flaviviridae
* Arbovirus encephalitides: Japanese encephalitis
* JEV
* Australian encephalitis
* MVEV
* KUNV
* Saint Louis encephalitis
* SLEV
* Usutu virus
* West Nile fever
* WNV
* Viral hemorrhagic fevers: Dengue fever
* DENV-1-4
* Yellow fever
* YFV
* Zika fever
* Zika virus
Togaviridae
* Arbovirus encephalitides: Eastern equine encephalomyelitis
* EEEV
* Western equine encephalomyelitis
* WEEV
* Venezuelan equine encephalomyelitis
* VEEV
* Chikungunya
* CHIKV
* O'nyong'nyong fever
* ONNV
* Pogosta disease
* Sindbis virus
* Ross River fever
* RRV
* Semliki Forest virus
Reoviridae
* Banna virus encephalitis
Tick
-borne
Bunyavirales
* Viral hemorrhagic fevers: Bhanja virus
* Crimean–Congo hemorrhagic fever (CCHFV)
* Heartland virus
* Severe fever with thrombocytopenia syndrome (Huaiyangshan banyangvirus)
* Tete virus
Flaviviridae
* Arbovirus encephalitides: Tick-borne encephalitis
* TBEV
* Powassan encephalitis
* POWV
* Viral hemorrhagic fevers: Omsk hemorrhagic fever
* OHFV
* Kyasanur Forest disease
* KFDV
* AHFV
* Langat virus
* LGTV
Orthomyxoviridae
* Bourbon virus
Reoviridae
* Colorado tick fever
* CTFV
* Kemerovo tickborne viral fever
Sandfly
-borne
Bunyavirales
* Adria virus (ADRV)
* Oropouche fever
* Oropouche virus
* Pappataci fever
* Toscana virus
* Sandfly fever Naples virus
Rhabdoviridae
* Chandipura virus
Mammal
-borne
Rodent
-borne
Arenaviridae
* Viral hemorrhagic fevers: Lassa fever
* LASV
* Venezuelan hemorrhagic fever
* GTOV
* Argentine hemorrhagic fever
* JUNV
* Brazilian hemorrhagic fever
* SABV
* Bolivian hemorrhagic fever
* MACV
* LUJV
* CHPV
Bunyavirales
* Hemorrhagic fever with renal syndrome
* DOBV
* HTNV
* PUUV
* SEOV
* AMRV
* THAIV
* Hantavirus pulmonary syndrome
* ANDV
* SNV
Herpesviridae
* Murid gammaherpesvirus 4
Bat
-borne
Filoviridae
* BDBV
* SUDV
* TAFV
* Marburg virus disease
* MARV
* RAVV
Rhabdoviridae
* Rabies
* ABLV
* MOKV
* DUVV
* LBV
* CHPV
Paramyxoviridae
* Henipavirus encephalitis
* HeV
* NiV
Coronaviridae
* SARS-related coronavirus
* SARS-CoV
* MERS-CoV
* SARS-CoV-2
Primate
-borne
Herpesviridae
* Macacine alphaherpesvirus 1
Retroviridae
* Simian foamy virus
* HTLV-1
* HTLV-2
Poxviridae
* Tanapox
* Yaba monkey tumor virus
Multiple
vectors
Rhabdoviridae
* Rabies
* RABV
* Mokola virus
Poxviridae
* Monkeypox
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| La Crosse encephalitis | c0014053 | 3,601 | wikipedia | https://en.wikipedia.org/wiki/La_Crosse_encephalitis | 2021-01-18T18:45:51 | {"gard": ["10820", "10925"], "mesh": ["D004670"], "umls": ["C0014053"], "orphanet": ["83483"], "wikidata": ["Q2713959"]} |
A biphasic primary lung neoplasm, belonging to the group of sarcomatoid lung carcinomas (SLCs). The tumor contains both an epithelial well-differentiated component, showing tubular architecture resembling the normal fetal lung, and a mesenchymal undifferentiated stroma with a so-called ''blastema-like'' configuration that resembles an embryonic lung.
## Epidemiology
PB is a rare tumor, accounting for less than 0.25% of all primary malignant lung tumors, with only around 350 cases having been reported in the literature so far. PB occurs almost exclusively in adults and has a peak incidence in the fourth decade of life (earlier than other forms of SLC), with a marked female predominance (70% of cases) and frequent association with tobacco smoking.
## Clinical description
Symptomatic patients present with nonspecific respiratory manifestations (cough, hemoptysis and chest pain). Other features may include dyspnea, fever, weight loss, and recurrent pneumonia. However, up to 40% of patients may be identified presymptomatically after a chest radiograph for another indication. PBs are usually well-demarcated solitary tumors (average size 10 cm) with cystic and necrotic features and are often located in the peripheral lung. Common sites of metastases include the brain, lymph nodes and liver.
## Etiology
Little is known about the pathogenesis and histogenesis of PB. Molecular studies indicate that mesenchymal and epithelial components are derived from a single precursor cell. Mutations in several genes (including TP53, CTNNB1 and EGFR) may be identified in some PB tumors.
## Diagnostic methods
Clinical laboratory and imaging studies are nonspecific and definitive diagnosis of PB requires identification of both the epithelial and mesenchymal components of the tumor, through histological studies on a resected specimen. Bronchoscopy and fine needle biopsy have been useful for diagnosis in some cases.
## Differential diagnosis
The differential diagnosis should include other forms of SLC (pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and adenocarcinoma (particularly fetal adenocarcinoma); see these terms). PB also has to be distinguished from the childhood tumor pleuropulmonary blastoma (see this term).
## Management and treatment
In many cases, the tumor is initially thought to be a bronchogenic carcinoma. Complete surgical resection with mediastinal lymph node dissection ensures both diagnosis and therapy. Adjuvant treatment, mostly consisting of radiotherapy, has been reported in a few cases, following incomplete resection, or in patients with N2 mediastinal involvement. For unresectable tumors, chemotherapy may be based on protocols used for sarcomas, including doxorubicin and ifosfamide.
## Prognosis
PB is an aggressive tumor and the prognosis has historically been reported as being poor: 5-year survival rates for patients with stage I disease were around 30%. In most recent reports, survival -adjusted by stage- is better than that for non-small cell lung cancer, especially in completely resected cases. Recurrences (occurring in 30-40% of patients) and metastases are common.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pulmonary blastoma | c0206629 | 3,602 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=64741 | 2021-01-23T17:05:14 | {"mesh": ["D018202"], "umls": ["C0206629"], "icd-10": ["C34.1", "C34.2", "C34.3", "C34.8", "C34.9"], "synonyms": ["Pneumoblastoma"]} |
Not to be confused with Athetoid cerebral palsy.
Athetosis
Bilateral athetosis
SpecialtyNeurology
Athetosis is a symptom characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases, arms, legs, neck and tongue.[1] Movements typical of athetosis are sometimes called athetoid movements. Lesions to the brain are most often the direct cause of the symptoms, particularly to the corpus striatum.[2] This symptom does not occur alone and is often accompanied by the symptoms of cerebral palsy, as it is often a result of this physical disability. Treatments for athetosis are not very effective, and in most cases are simply aimed at managing the uncontrollable movement, rather than the cause itself.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Asphyxia
* 2.2 Neonatal jaundice
* 2.3 Thalamic stroke
* 2.4 Fahr's syndrome
* 3 Treatments
* 4 Related disorders
* 4.1 Choreoathetosis
* 4.2 Cerebral palsy
* 4.3 Pseudoathetosis
* 5 Social implications
* 6 History
* 7 Research directions
* 8 See also
* 9 References
* 10 External links
## Signs and symptoms[edit]
Athetosis can vary from mild to severe motor dysfunction; it is generally characterized by unbalanced, involuntary movements of muscle and a difficulty maintaining a symmetrical posture. The associated motor dysfunction can be restricted to a part of body or present throughout the body, depending on the individual and the severity of the symptom. One of the pronounced signs can be observed in the extremities in particular, as the writhing, convoluted movement of the digits.[1] Athetosis can appear as early as 18 months from birth with first signs including difficulty feeding, hypotonia, spasm, and involuntary writhing movements of the hands, feet, and face, which progressively worsen through adolescence and at times of emotional distress.[3] Athetosis is caused by lesions in several brain areas such as the hippocampus and the motor thalamus, as well as the corpus striatum;[2] therefore children during the developmental age could possibly suffer from severe communication deficits such as speech impairment, hearing loss, and failed or delayed acquirement of sitting balance, although most of people with athetosis have normal or near-normal intelligence.[3]
## Causes[edit]
Athetosis is a symptom primarily caused by the marbling, or degeneration of the basal ganglia.[citation needed] This degeneration is most commonly caused by complications at birth or by Huntington's disease, in addition to rare cases in which the damage may also arise later in life due to stroke or trauma.[citation needed] The two complications of particular interest are intranatal asphyxia and neonatal jaundice.
### Asphyxia[edit]
Asphyxia directly causes basal ganglia damage due to lack of oxygen and therefore, insufficient nutrient supply.[citation needed] The lesions caused by asphyxia are most prominent on the caudate nucleus and the putamen.[4] However, a less-studied consequence of the resulting hypoxia is its effect on the concentrations of the neurotransmitter dopamine within the synapses of neurons in the basal ganglia. Hypoxia leads to an increase in the extracellular dopamine levels and therefore, an increase in the activity of the dopaminergic neurons. Furthermore, this increase in extracellular concentration is not caused by an increase in the neurotransmitter synthesis, but instead on inhibiting its reuptake back into the neurons and glial cells.[5] Therefore, there is an increased dopaminergic effect as dopamine remains in the synapse at higher concentrations leading to additional post-synaptic response. As a result, the uncontrollable writhing motions witnessed with athetosis deal with the over-activity of synapses within the basal ganglia.
### Neonatal jaundice[edit]
Neonatal jaundice is the other chief complication that leads to the basal ganglia damage associated with this condition. Jaundice is caused by hyperbilirubinemia, or abnormally high levels of bilirubin in the blood. Bilirubin is usually bound to albumin immediately and sent to the liver. However, in neonatal jaundice, the concentration of bilirubin overwhelms that of albumin and some of the bilirubin remains unconjugated and can enter the brain through the blood–brain barrier.[6] Normally bilirubin would not be able to diffuse across the blood–brain barrier, but in infants, the barrier is immature and has higher permeability. Bilirubin is toxic as it prevents the phosphorylation of many proteins, including synapsin I which binds vesicles in the presynaptic terminal.[7] Therefore, it directly inhibits the exocytosis of neurotransmitters and severely hinders the synapses it affects. In autopsies of children who suffered from neonatal jaundice, chronic changes of neuronal loss, gliosis and demyelination were observed in the basal ganglia and more specifically within the globus pallidus.[6]
### Thalamic stroke[edit]
Another study was done where the onset of athetoid movement followed a thalamic stroke.[citation needed] The thalamus is part of a pathway that is involved with the cortical feedback loop in which signals from the cortex are relayed through the striatum, pallidus and thalamus before making it back to the cortex.[8] The striatum receives excitatory inputs from the cortex and inhibits the pallidum. By doing so it frees the thalamus from pallidal inhibition allowing the thalamus to send excitatory outputs to the cortex. Therefore, the lesions to the thalamus or any other part of this feedback loop can result in movement disorders as they can alter the reactivity of one towards the other.[8] Also, in a case of people with thalamic stroke, a majority suffered severe sensory deficits and ataxia. It is proposed that this loss of proprioception and the ensuing loss of synergic stabilization may also lead to abnormal movements, such as those dealt with in athetosis.[8]
### Fahr's syndrome[edit]
Main article: Fahr's syndrome
## Treatments[edit]
There are several different treatment approaches to dealing with athetosis. The most common methods are the use of drugs, surgical intervention, and retraining movements of the afflicted person. It is suggested that training a person to relearn movements can be helpful in select situations. Though, generally, this type of treatment will not work, in certain cases it can be found to be very helpful in treating the symptom of athetosis.[9]
Drugs can also be used in the treatment of athetosis, however their collective effectiveness is not very convincing.[10] There is not a single drug that is a standard among treatment. Many different medicines can be used, including:
* Artane
* Cogentin[11]
* Curare,[9] though not practical due to respiratory paralysis
* Tetrabenazine
* Haloperidol
* Thiopropazate
* Diazepam
Most instances of drug use where the symptoms seem to be lessened tend to be in more mild cases of athetosis.[10]
Treatment by surgical intervention can obviously have the most immediate impact, again however, it is not a cure-all. In patients that have cerebral palsy as the cause of their athetosis, it has been demonstrated that a subthalamotomy tends to help relieve the extent of athetosis in approximately half of patients. Additionally, late 19th and early 20th century surgical accounts state that athetosis can be relieved by the removal of a part of the cerebral motor cortex or by cutting a part of the posterior spinal roots.[12] Patients who undergo surgical treatment to relieve the athetosis often see significant improvement in the control of their limbs and digits.[9] While surgery is often very beneficial in the short term and can produce near immediate results, in the long term it has been seen that its effects are not incredibly long lasting.[4]
## Related disorders[edit]
### Choreoathetosis[edit]
Chorea is another condition which results from damage to the basal ganglia. Similar to athetosis, it results from mutations affecting the pallidum inhibition of the thalamus as well as increased dopaminergic activity at the level of the striatum.[13] Considering the etiology of both disorders are fairly similar, it comes as no surprise that chorea and athetosis can and usually do occur together in a condition called choreoathetosis.
### Cerebral palsy[edit]
Athetosis is a commonly occurring symptom in the disease cerebral palsy.[14] Of all people with the disease, between 16%[15] and 25%[4] of them actually exhibit the symptom of athetosis. A component of this is the finding that most often the symptoms that involve athetosis occur as a part of choreoathetosis as opposed to athetosis alone.[16]
It is also noteworthy that the presence of athetosis in cerebral palsy (as well as other conditions) causes a significant increase in a person’s basal resting metabolic rate. It has been observed that those who have cerebral palsy with athetosis require approximately 500 more Calories per day than their non-cerebral palsy non-athetoid counterpart.[15]
### Pseudoathetosis[edit]
Pseudoathetosis is a movement disorder, very similar to athetosis, in which the symptoms are not differentiable from those of actual athetosis, however the underlying cause is different. While actual athetosis is caused by damage to the brain, specifically in the basal ganglia,[4] pseudoathetosis is caused by the loss of proprioception.[17] The loss in proprioception is caused by damage to the area between the primary somatosensory cortex and the muscle spindles and joint receptors. Additionally, when observing an MRI, it can be seen that in the brain of a pseudoathetoid patient, lesions on the brain are not seen in the basal ganglia,[18] the area that is oftentimes the cause of athetosis.[4]
## Social implications[edit]
Athetosis is characterized as a symptom that is present in many forms of central nervous system disorders that affect the body movement coordination, such as cerebral palsy. Children may struggle to engage in social communication, since the poor coordination of the tongue and mouth muscles can reduce their speech ability and hinder their social interaction to a greater degree.[19] The caregivers of the affected children are encouraged to closely monitor their nutrition and growth and to provide them with hearing aids in order to relieve their symptoms as well as support their academic plans.[20] A growing number of patients is shown to benefit from communication devices such as shorthand typing programs and computer speech devices, as well as simple picture boards.[19]
Patients living with the disorder into their adulthood often have trouble being involved in daily activities such as eating, walking, dressing, as well as performing everyday tasks. They are consistently faced with challenges that limit their ability to live on their own. They are more reluctant to be involved in social activities and romantic relationships and more likely to develop poor self-esteem and self-image related to their physical limitations as well as cognitive disabilities, though such habitual thinking is shown to decline when they feel they are accepted and supported by their peers.[21] Patients are also inclined to associate themselves with people who tend not to be engaged in physical activities, according to the September 2008 issue of “Journal of Physical Activity and Health.”[22]
## History[edit]
The first noted case of athetosis was discovered by W. A. Hammond and described in his book Diseases of the Nervous System in 1871.[9] Hammond was also the person who created the term "athetosis", Greek for "without position".[23] In his initial description of athetosis, the extent of the uncontrolled movement was limited to the fingers and toes. In association with this, he noted that the patients' calves and forearms were oftentimes flexed and that movements were generally slow. Over the period of time leading into the late 20th century, the definition of athetosis was expanded to include movements of the neck, tongue, face, and even the trunk. Along with the expansion of the symptoms came the recognition that it was a part of many medical conditions, including cerebral palsy and stroke.[23]
## Research directions[edit]
As athetosis is relatively difficult to treat, efforts are being made to help those with the condition live and perform tasks more effectively and more efficiently. One such example of work that has been recently undertaken is a project to help those affected with athetosis to use a computer with more ease. Software for the control of the computer uses joysticks that perform linear filtering to aid in control.[24]
An additional possible treatment option for those afflicted with the symptom is neurostimulation. Studies have begun, and in cerebral palsy patients affected with dystonia-choreoathetosis, it has been demonstrated that neurostimulation has been an effective treatment in lessening symptoms in patients. There has not been a tremendous amount of experimentation, though, in this as a possible treatment option.[25]
## See also[edit]
* Chorea
* Dyskinesia
* Dystonia
* Pupillary athetosis
## References[edit]
1. ^ a b Walker, Kenneth H (1990). "Ch. 70 Involuntary Movements". Clinical Methods: The History, Physical, and Laboratory (3rd ed.). PMID 21250235.
2. ^ a b "Athetosis". Health Database - Medical Ailments & Diseases. Retrieved March 22, 2011.
3. ^ a b McNeil, Malcolm R. (2009). Clinical Management of Sensorimotor Speech Disorders. Thieme. ISBN 978-1-58890-514-7.
4. ^ a b c d e Foley J (April 1983). "The athetoid syndrome. A review of a personal series". J. Neurol. Neurosurg. Psychiatry. 46 (4): 289–98. doi:10.1136/jnnp.46.4.289. PMC 1027350. PMID 6341510.
5. ^ Akiyama Y, Koshimura K, Ohue T, Lee K, Miwa S, Yamagata, S (September 1991). "Effects of hypoxia on the activity of the dopaminergic neuron system in the rat striatum as studied by in vivo brain microdialysis". Journal of Neurochemistry. 57 (3): 997–1002. doi:10.1111/j.1471-4159.1991.tb08249.x. PMID 1861163.
6. ^ a b Martich-Kriss, V; Kollias, SS; Ball WS, Jr (April 1995). "MR findings in kernicterus". American Journal of Neuroradiology. 16 (4 Suppl): 819–21. PMID 7611048.
7. ^ Hansen, TW (December 2001). "Bilirubin brain toxicity". Journal of Perinatology. 21 Suppl 1: S48–51, discussion S59–62. doi:10.1038/sj.jp.7210634. PMID 11803417.
8. ^ a b c Handley, A; Medcalf, P; Hellier, K; Dutta, D (May 2009). "Movement disorders after stroke". Age and Ageing. 38 (3): 260–6. doi:10.1093/ageing/afp020. PMID 19276093.
9. ^ a b c d Putnam T (May 1939). "Athetosis". Yale J. Biol. Med. 11 (5): 459–465. PMC 2602263. PMID 21433835.
10. ^ a b Mawdsley C (December 1975). "Diseases of the central nervous system. Involuntary movements". Br. Med. J. 4 (5996): 572–4. doi:10.1136/bmj.4.5996.572. PMC 1675885. PMID 1203674.
11. ^ Polzin, Scott J., MS, and Teresa G. Odle. "Cerebral palsy." Gale Encyclopedia of Medicine. Thomson Gale, 2006. NA. Health Reference Center Academic. Gale.
12. ^ Laitinen LV (August 1970). "Neurosurgery in cerebral palsy". J. Neurol. Neurosurg. Psychiatry. 33 (4): 513–8. doi:10.1136/jnnp.33.4.513. PMC 493511. PMID 4918461.
13. ^ Bhidayasiri, R; Truong, DD (September 2004). "Chorea and related disorders". Postgraduate Medical Journal. 80 (947): 527–34. doi:10.1136/pgmj.2004.019356. PMC 1743104. PMID 15356354.
14. ^ Rodriguez SP, Ding D, Riviere SP (September 2010). "Algorithms for target prediction for computer users with athetosis". 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology. 2010. pp. 491–494. doi:10.1109/iembs.2010.5627118. ISBN 978-1-4244-4123-5. PMC 3253859. PMID 21096307.
15. ^ a b Johnson RK, Goran MI, Ferrara MS, Poehlman ET (February 1996). "Athetosis increases resting metabolic rate in adults with cerebral palsy". J. Am. Diet. Assoc. 96 (2): 145–8. doi:10.1016/S0002-8223(96)00043-0. PMID 8557940.
16. ^ O'Shea TM (December 2008). "Diagnosis, treatment, and prevention of cerebral palsy". Clin. Obstet. Gynecol. 51 (4): 816–28. doi:10.1097/GRF.0b013e3181870ba7. PMC 3051278. PMID 18981805.
17. ^ Lo YL, See S (November 2010). "Images in clinical medicine. Pseudoathetosis". N. Engl. J. Med. 363 (19): e29. doi:10.1056/NEJMicm0907786. PMID 21047218.
18. ^ Salih F, Zimmer C, Meierkord H (March 2007). "Parietal proprioceptive loss with pseudoathetosis". J. Neurol. 254 (3): 396–7. doi:10.1007/s00415-006-0382-x. PMID 17345036.
19. ^ a b Jeff Brody (2005). "Social Problems with Cerebral Palsy". Cerebral Palsy Lawyer - Birth Injury Attorney. Cerebral Palsy Source. Retrieved March 21, 2011.
20. ^ T. Michael O’Shea (December 2009). "Diagnosis, Treatment, and Prevention of Cerebral Palsy in Near-Term/Term Infants". Clinical Obstetrics and Gynecology. 51 (4): 816–28. doi:10.1097/GRF.0b013e3181870ba7. PMC 3051278. PMID 18981805.
21. ^ Lehrman, Mary (10 May 2010). "The Social, Emotional, & Psychological Effects Of Adults With Cerebral Palsy". Demand Media, Inc. Retrieved March 22, 2011.
22. ^ Gaskin, Cadeyrn; Morris, Tony (September 2008). "Physical Activity, Health-Related Quality of Life, and Psychosocial Functioning of Adults With Cerebral Palsy". Journal of Physical Activity and Health.
23. ^ a b Morris JG, Jankelowitz SK, Fung VS, Clouston PD, Hayes MW, Grattan-Smith P (November 2002). "Athetosis I: historical considerations". Mov. Disord. 17 (6): 1278–80. doi:10.1002/mds.10267. PMID 12465068.
24. ^ Lopez JV, Sibenaller S, Ding D, Riviere CN (2007). "Toward filtering of athetoid movement with neural networks". Engineering in Medicine and Biology Society. 29th Annual International Conference of the IEEE. doi:10.1109/iembs.2007.4352569.
25. ^ Vidailhet M, Yelnik J, Lagrange C, et al. (August 2009). "Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study". Lancet Neurol. 8 (8): 709–17. doi:10.1016/S1474-4422(09)70151-6. PMID 19576854.
## External links[edit]
Classification
D
* ICD-10: R25.8
* ICD-9-CM: 781.0
* MeSH: D001264
* DiseasesDB: 16662
* SNOMED CT: 44913001
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
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* Cerebellar ataxia
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SA
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* both:
* Amyotrophic lateral sclerosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Athetosis | c0004158 | 3,603 | wikipedia | https://en.wikipedia.org/wiki/Athetosis | 2021-01-18T18:57:28 | {"gard": ["5863"], "mesh": ["D001264"], "umls": ["C1845265", "C0004158"], "icd-9": ["781.0"], "icd-10": ["R25.8"], "wikidata": ["Q755524"]} |
A Howell–Jolly body (marked by arrow) within an erythrocyte
A Howell–Jolly body is a cytopathological finding of basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes. During maturation in the bone marrow, late erythroblasts normally expel their nuclei; but, in some cases, a small portion of DNA remains. Its presence usually signifies a damaged or absent spleen, because a healthy spleen would normally filter this type of red blood cell.
The Howell–Jolly body is named after William Henry Howell[1] and Justin Marie Jolly.[2][3]
## Contents
* 1 Appearance
* 2 Causes
* 3 References
* 4 External links
## Appearance[edit]
Howell–Jolly bodies: small, round inclusions seen in erythrocytes (peripheral blood – MGG stain)
This DNA appears as a basophilic (purple) spot on the otherwise eosinophilic (pink) erythrocyte on a standard H&E stained blood smear. These inclusions are normally removed by the spleen during erythrocyte circulation, but will persist in individuals with functional hyposplenia or asplenia.
## Causes[edit]
Howell–Jolly bodies are seen with markedly decreased splenic function. Common causes include asplenia (post-splenectomy) or congenital absence of spleen (heterotaxy syndrome with asplenia). Spleens are also removed for therapeutic purposes in conditions like hereditary spherocytosis, trauma to the spleen, and autosplenectomy caused by sickle cell anemia. Other causes are radiation therapy involving the spleen, such as that used to treat Hodgkin lymphoma.
Howell–Jolly bodies are also seen in amyloidosis, severe hemolytic anemia, megaloblastic anemia, hereditary spherocytosis, and myelodysplastic syndrome (MDS). The bodies can also can be seen in premature infants.
## References[edit]
1. ^ Howell, W. H. "The life-history of the formed elements of the blood, especially the red blood corpuscles" (PDF). Journal of Morphology. New York. 4 (1): 57–116. doi:10.1002/jmor.1050040105.
2. ^ synd/1596 at Who Named It?
3. ^ Jolly, J (1908). Recherches sur la formation des globules rouges des mammifères (in French). 58. Paris: Comptes rendus de la Société de Biologie. pp. 528–531.
## External links[edit]
* Digital Pathology, Brown University: Howell-Jolly Bodies
* v
* t
* e
Blood film findings
Red blood cells
Size
* Anisocytosis
* Macrocytosis
* Microcytosis
Shape
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Colour
* Anisochromia
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Other
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* Rouleaux
White blood cells
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Granulocytes
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* Alder–Reilly anomaly
* Jordans' anomaly
* Birbeck granules
* Left shift
Other
* Auer rod
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Howell–Jolly body | c0020058 | 3,604 | wikipedia | https://en.wikipedia.org/wiki/Howell%E2%80%93Jolly_body | 2021-01-18T19:00:58 | {"mesh": ["D004908"], "umls": ["C0020058"], "wikidata": ["Q1291359"]} |
Multiple myeloma is a cancer that develops in the bone marrow, the spongy tissue found in the center of most bones. The bone marrow produces red blood cells, which carry oxygen throughout the body; white blood cells, which form the body's defenses (immune system); and platelets, which are necessary for blood clotting.
Multiple myeloma is characterized by abnormalities in plasma cells, a type of white blood cell. These abnormal cells multiply out of control, increasing from about one percent of cells in the bone marrow to the majority of bone marrow cells. The abnormal cells form tumors within the bone, causing bone pain and an increased risk of fractures. If the tumors interfere with nerves near the bones, numbness or weakness in the arms or legs can occur. Affected individuals may also experience a loss of bone tissue, particularly in the skull, spine, ribs, and pelvis. The deterioration of bone can result in an excess of calcium in the blood (hypercalcemia), which can lead to nausea and loss of appetite, excessive thirst, fatigue, muscle weakness, and confusion.
The abnormal plasma cells in multiple myeloma produce proteins that impair the development of normal blood cells. As a result, affected individuals may have a reduced number of red blood cells (anemia), which can cause fatigue, weakness, and unusually pale skin (pallor); a low number of white blood cells (leukopenia), which can result in a weakened immune system and frequent infections such as pneumonia; and a reduced number of platelets (thrombocytopenia), which can lead to abnormal bleeding and bruising. Kidney problems can also occur in this disorder, caused by hypercalcemia or by toxic proteins produced by the abnormal plasma cells.
People with multiple myeloma typically develop the disorder around age 65. Over time, affected individuals can develop life-threatening complications, but the rate at which this happens varies widely. Some affected individuals are diagnosed incidentally when tests are done for other purposes and do not experience symptoms for years.
## Frequency
Multiple myeloma is considered a rare cancer; it accounts for about 10 percent of cancers of the blood and blood-forming tissues, and between one and two percent of all cancers. Multiple myeloma occurs in approximately 4 per 100,000 people per year; there are currently about 100,000 affected individuals in the United States.
## Causes
The cause of multiple myeloma is unclear. Somatic mutations, which are genetic changes that are not inherited but occur during an individual's lifetime in certain cells (in this case the plasma cells), have been identified in people with multiple myeloma. Some of these changes affect genes that play a critical role in regulating cell division by preventing cells from dividing too rapidly or in an uncontrolled way. Mutations in these genes may interfere with proper control (regulation) of cell growth and division (proliferation), resulting in the excessive proliferation of plasma cells that characterizes multiple myeloma.
Abnormal exchanges of genetic material between chromosomes (translocations) are common somatic events in multiple myeloma. The translocations most often involve an exchange between chromosome 14 and another chromosome. Genes that control cell growth and division are likely affected by these translocations. Researchers are working to determine what role these genetic and chromosomal changes play in the development and progression of multiple myeloma.
Close relatives of people with multiple myeloma have an increased risk of developing it themselves, suggesting that inherited variations in certain genes may contribute to the development of the disorder in some individuals. By contrast, certain other inherited genetic variations appear to reduce the risk of developing multiple myeloma.
Nongenetic factors that increase the risk of developing multiple myeloma include previous radiation therapy or other radiation exposure. Exposure to certain chemicals including benzene has also been found to increase myeloma risk. Benzene, a known carcinogen, is a petroleum product widely used as an industrial solvent and a gasoline additive.
### Learn more about the genes and chromosome associated with Multiple myeloma
* BRAF
* FGFR3
* chromosome 14
Additional Information from NCBI Gene:
* CCND1
* FCRL4
* IRF4
* LIG4
* MAF
* PWWP3A
## Inheritance Pattern
This condition is generally not inherited but arises from somatic mutations in plasma cells. An increased risk of developing multiple myeloma seems to run in some families, but the inheritance pattern is unknown.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Multiple myeloma | c0268381 | 3,605 | medlineplus | https://medlineplus.gov/genetics/condition/multiple-myeloma/ | 2021-01-27T08:25:19 | {"gard": ["7108"], "mesh": ["D000075363"], "omim": ["254500"], "synonyms": []} |
Autosomal recessive spastic paraplegia type 27 is a rare, pure or complex hereditary spastic paraplegia characterized by a variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Autosomal recessive spastic paraplegia type 27 | c1836899 | 3,606 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=101007 | 2021-01-23T17:01:56 | {"mesh": ["C563807"], "omim": ["609041"], "umls": ["C1836899"], "icd-10": ["G11.4"], "synonyms": ["SPG27"]} |
A number sign (#) is used with this entry because of evidence that congenital disorder of glycosylation type IIp (CDG2P) is caused by homozygous or compound heterozygous mutation in the TMEM199 gene (616815) on chromosome 17q11.
Description
Congenital disorder of glycosylation type IIp (CDG2P) is an autosomal recessive metabolic disorder characterized by mild liver dysfunction, which may be found incidentally during adolescence. Laboratory abnormalities include elevated liver enzymes and alkaline phosphatase, coagulation factor deficiencies, hypercholesterolemia, and low ceruloplasmin. Serum isoelectric focusing of proteins shows a combined defect of N- and O-glycosylation, suggestive of a Golgi defect (summary by Jansen et al., 2016).
For an overview of congenital disorders of glycosylation, see CDG1A (212065) and CDG2A (212066).
Clinical Features
Jansen et al. (2016) reported 4 patients from 3 unrelated families with a mild metabolic disorder primarily affecting the liver. Three of the patients, including 2 sibs born of consanguineous Greek parents, were found to have elevated liver enzymes on routine blood tests during adolescence. Psychomotor development was normal in these 3 patients. Additional laboratory abnormalities included reduced ceruloplasmin, hypercholesterolemia, increased alkaline phosphatase, and decreased coagulation factors. Liver imaging and/or biopsy studies showed steatosis. Some of these laboratory abnormalities fluctuated or improved with age. Liver biopsy of one patient at the age of 41 years showed mild fibrosis, vacuolization of hepatocytes, dilation and vesiculation of the Golgi apparatus and/or endoplasmic reticulum, and mitochondrial abnormalities, such as fragmented cristae and altered inner matrix. This patient had been reported by Calvo et al. (2008). The fourth patient was a 23-year-old Greek woman who was noted to have hypotonia and psychomotor disability in early childhood. She was later found to have increased liver enzymes and alkaline phosphatase, hypercholesterolemia, and low ceruloplasmin; she was lost to follow-up. All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation.
Inheritance
The transmission pattern of CDG2P in the families reported by Jansen et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 4 patients from 3 unrelated families with CDG2P, Jansen et al. (2016) identified homozygous or compound heterozygous mutations in the TMEM199 gene (616815.0001-616815.0004). The mutations in the first 2 families were found by whole-exome sequencing; all mutations segregated with the disorder in the families. Mass spectrometry of the transferrin protein and total plasma N-glycans in 1 patient showed an accumulation of incompletely synthesized glycans lacking galactose and sialic acid compared to controls. Patient fibroblasts showed a generalized defect in Golgi processing of protein-linked glycans compared to controls, and this defect was rescued after transduction with wildtype TMEM199. Western blot analysis of patient cells in 2 families showed reduced TMEM199 protein levels, but direct functional studies of the variants were not performed.
INHERITANCE \- Autosomal recessive ABDOMEN Liver \- Liver dysfunction \- Liver steatosis \- Liver fibrosis, mild \- Copper accumulation (in some patients) MUSCLE, SOFT TISSUES \- Hypotonia (1 patient) NEUROLOGIC Central Nervous System \- Delayed psychomotor development (1 patient) HEMATOLOGY \- Decreased serum coagulation factors LABORATORY ABNORMALITIES \- Type 2 pattern of transferrin, indicating N-glycosylation defect \- Abnormal ApoC-III glycosylation, indicating O-glycosylation defect \- Abnormal liver enzymes \- Low ceruloplasmin \- Increased alkaline phosphatase \- Hypercholesterolemia MISCELLANEOUS \- Onset in adolescence \- Mild disorder \- Some laboratory abnormalities may fluctuate or improve with time \- Four patients from 3 unrelated families have been reported (last curated February 2016) MOLECULAR BASIS \- Caused by mutation in the transmembrane protein 199 gene (TMEM199, 616815.0001 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIp | c4225190 | 3,607 | omim | https://www.omim.org/entry/616829 | 2019-09-22T15:47:47 | {"doid": ["0070268"], "omim": ["616829"], "orphanet": ["466703"], "synonyms": ["CDG-IIp", "CDG IIp", "Alternative titles", "Congenital disorder of glycosylation type 2p", "Congenital disorder of glycosylation type IIp", "CDG syndrome type IIp", "CDG2P", "Carbohydrate deficient glycoprotein syndrome type IIp"]} |
In Finland Furuhjelm et al. (1968) found an antibody that tests for a previously unknown antigen called Ul(a). The antigen was present in 2.6% of Helsinki donors. Independence from Kell, Yt and Diego systems was not yet proved but it was independent of other systems. The Ul(a) locus may be within measurable distance of the ABO and adenylate kinase loci.
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| BLOOD GROUP--Ul SYSTEM | None | 3,608 | omim | https://www.omim.org/entry/112000 | 2019-09-22T16:44:11 | {"omim": ["112000"]} |
Janus kinase 3 deficiency
Other namesJAK3 deficiency
JAK3 (Janus kinase 3) deficiency is a dysfunction in cytokine receptor signalling and their production of cytokines.
JAK3 is a tyrosine protein kinase, an enzyme that is encoded by the JAK3 gene. It is a kinase that is activated only by cytokines whose receptors contain the common gamma chain subunit (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21). JAK3 is involved in iniating signalling for the cytokine receptors because they itself lack enzymatic activity. Once activated, the JAK kinase phosphorylates specific tyrosine residues on the cytokine receptor subunits which then activate STAT transcription factors. JAK3 helps to regulate differentiation and maturation of B cells, T cells and NK cells.
Mutations in the JAK3 gene can cause dysfunction of the kinase leading to autosomal severe combined immunodeficiency (SCID) disease [1] or on the contrary, the activation of mutated JAK3 can lead to development of leukemia. The JAK3 tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases.[2]
Patients with JAK3-deficiency lack the necessary immune cells, meaning that they do not have T cells and NK cells but have normal level but poorly functioning B cells. The necessary immune cells have resistance and ability to fight off certain bacteria, viruses, and fungi. The patients are then prone to repeated and persistent infections that can be very serious or life-threatening.[3]
Affected infants typically develop chronic diarrhea, a fungal infection in the mouth called oral thrush (candidiasis), pneumonia, and skin rashes. Constant illness also causes slower development of the affected individuals. Without treatment, people with JAK3-deficient SCID usually live only into early childhood.[3]
## Contents
* 1 Diagnosis
* 2 Treatment
* 3 See also
* 4 References
* 5 Further reading
## Diagnosis[edit]
In suspection of a genetic mutation after physical examination, checking personal and family medical history and laboratory tests (measuring levels of certain substances or biochemical test of the blood and urine) can be used genetic testing as certain diagnosis. Genetic testing identifies changes in chromosomes, genes, or proteins. However, some conditions do not have a specific genetic test; either the genetic cause of the condition is unknown or a test has not yet been developed. In these cases, a combination of the approaches listed above may be used to make a diagnosis.
## Treatment[edit]
The treatment for JAK3 deficiency is allogeneic hematopoietic stem cell transplantation, which has been demonstrated to be life-saving for affected patients.[4]
Another option is gene therapy that has the potential to become an alternative treatment for JAK3 deficiency. Because of the clinical and biochemical similarities between JAK3 deficiency and X-linked severe combined immunodeficiency, genetic correction and engraftment of autologous hematopoietic stem cells can presume restoring of immunity in JAK3-deficient patients.[citation needed]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ Notarangelo, L. D.; Mella, P.; Jones, A.; de Saint Basile, G.; Savoldi, G.; Cranston, T.; Vihinen, M.; Schumacher, R. F. (October 2001). "Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiency". Human Mutation. 18 (4): 255–263. doi:10.1002/humu.1188. ISSN 1098-1004. PMID 11668610.
2. ^ Degryse, Sandrine; Bornschein, Simon; de Bock, Charles E.; Leroy, Emilie; Vanden Bempt, Marlies; Demeyer, Sofie; Jacobs, Kris; Geerdens, Ellen; Gielen, Olga (25 January 2018). "Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL". Blood. 131 (4): 421–425. doi:10.1182/blood-2017-07-797597. ISSN 1528-0020. PMC 5796683. PMID 29187379.
3. ^ a b Reference, Genetics Home. "JAK3-deficient severe combined immunodeficiency". Genetics Home Reference. Retrieved 2019-08-29.
4. ^ Roberts, Joseph L.; Lengi, Andrea; Brown, Stephanie M.; Chen, Min; Zhou, Yong-Jie; O'Shea, John J.; Buckley, Rebecca H. (2004-03-15). "Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation". Blood. 103 (6): 2009–2018. doi:10.1182/blood-2003-06-2104. ISSN 0006-4971. PMID 14615376.
## Further reading[edit]
* Notarangel, Luigi (2005). "JAK3 deficiency, (SCID T-B+)" (PDF). Orphanet.
* https://ghr.nlm.nih.gov/condition/jak3-deficient-severe-combined-immunodeficiency
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Janus kinase 3 deficiency | c1833275 | 3,609 | wikipedia | https://en.wikipedia.org/wiki/Janus_kinase_3_deficiency | 2021-01-18T18:42:58 | {"mesh": ["C563440"], "omim": ["600802"], "orphanet": ["35078"], "synonyms": ["T-B+ SCID due to JAK3 deficiency"], "wikidata": ["Q6155971"]} |
This article is about the swelling of an eyelid. For the article of a pen with pigs, see Sty. For other uses of Sty, see Sty (disambiguation).
Stye
Other namesSty, hordeolum[1]
An external stye on the upper eyelid
Pronunciation
* Stye /staɪ/, hordeolum /hɔːrˈdiːələm/
SpecialtyOphthalmology, optometry
SymptomsRed tender bump at the edge of the eyelid[1]
Usual onsetAny age[2]
DurationFew days or weeks[3]
CausesUsually bacterial infection by Staphylococcus aureus[3]
Differential diagnosisChalazion[4]
TreatmentWarm compresses, antibiotic eye ointment[5][6]
A stye, also known as a hordeolum, is a bacterial infection of an oil gland in the eyelid.[4] This results in a red tender bump at the edge of the eyelid.[1][5] The outside or the inside of the eyelid can be affected.[3]
The cause of a stye is usually a bacterial infection by Staphylococcus aureus.[3][6] The internal ones are due to infection of the meibomian gland while the external ones are due to an infection of the gland of Zeis.[5] A chalazion on the other hand is a blocked oil gland without infection.[4] A chalazion is typically in the middle of the eyelid and not painful.[5]
Often a stye will go away without any specific treatment in a few days or weeks.[3] Recommendations to speed improvement include warm compresses.[5] Occasionally antibiotic eye ointment may be recommended.[6] While these measures are often recommended, there is little evidence for use in internal styes.[3] The frequency at which styes occur is unclear, though they may occur at any age.[2]
## Contents
* 1 Signs and symptoms
* 1.1 Complications
* 2 Cause
* 3 Prevention
* 4 Treatment
* 4.1 Antibiotics
* 4.2 Procedures
* 4.3 Alternative medicine
* 5 Prognosis
* 6 Etymology
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
Stye of the upper eyelid
8-year-old boy with an external hordeolum of lower lid
The first sign of a stye is a small, yellowish spot at the center of the bump that develops as pus and expands in the area.[7]
Other stye symptoms may include:
* A lump on the top or bottom eyelid
* Localized swelling of the eyelid
* Localized pain
* Redness
* Tenderness
* Crusting of the eyelid margins
* Burning in the eye
* Droopiness of the eyelid
* Scratchy sensation on the eyeball (itching)
* Blurred vision
* Mucous discharge in the eye
* Irritation of the eye[8]
* Light sensitivity
* Tearing
* Discomfort during blinking[9]
* Sensation of a foreign body in the eye
### Complications[edit]
Stye complications occur in very rare cases. However, the most frequent complication of styes is progression to a chalazion that causes cosmetic deformity, corneal irritation, and often requires surgical removal.[10] Complications may also arise from the improper surgical lancing, and mainly consist of disruption of lash growth, lid deformity or lid fistula. Large styes may interfere with one's vision.
Eyelid cellulitis is another potential complication of eye styes, which is a generalized infection of the eyelid. Progression of a stye to a systemic infection (spreading throughout the body) is extremely rare, and only a few instances of such spread have been recorded.[11]
## Cause[edit]
A stye is caused by a bacterial infection. The bacteria is Staphylococcus aureus in about 95% of cases.[12] The infection leads to the blocking of an oil gland at the base of the eyelash. Styes are experienced by people of all ages. Styes can be triggered by poor nutrition, sleep deprivation, lack of hygiene, lack of water, and rubbing of the eyes. Styes can be secondary to blepharitis or a deficiency in immunoglobulin.[13]
## Prevention[edit]
Stye prevention is closely related to proper hygiene. Proper hand washing can reduce the risks of developing not only styes, but also many other types of infections.
Upon awakening, application of a warm washcloth to the eyelids for one to two minutes may be beneficial in decreasing the occurrence of styes by liquefying the contents of the oil glands of the eyelid and thereby preventing blockage.[14]
To prevent styes, cosmetics and cosmetic eye tools should not be shared among people. Like with all infections, regular hand washing is essential, and the eyes should not be rubbed or touched with unclean hands. Contaminated eye makeup should be discarded and sharing of washcloths or face towels should be curtailed, to avoid spreading the infection between individuals.[15][16] Breaking the stye may spread bacteria contained in the pus and should be avoided.[17]
## Treatment[edit]
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Most cases of styes resolve on their own within one to two weeks, without professional care.[3] The primary treatment is application of warm compresses. As a part of self-care at home, people may cleanse the affected eyelid with tap water or with a mild, nonirritating soap or shampoo (such as baby shampoo) to help clean crusted discharge. Cleansing must be done gently and while the eyes are closed to prevent eye injuries.[18]
People with styes should avoid eye makeup (e.g., eyeliner), lotions, and wearing contact lenses, since these can aggravate and spread the infection (sometimes to the cornea).[19] People are advised not to lance the stye themselves, as serious infection can occur.[19] Pain relievers such as acetaminophen may be used.
### Antibiotics[edit]
Evidence to support the use of antibiotic eye ointment is poor.[6] Occasionally erythromycin ophthalmic ointment is recommended.[20] Other antibiotics, such as chloramphenicol or amoxicillin may also be used.[21] Chloramphenicol is used successfully in many parts of the world, but contains a black box warning in the United States due to concerns about aplastic anemia, which on rare occasions can be fatal.
Antibiotics are normally given to people with multiple styes or with styes that do not seem to heal, and to people who have blepharitis or rosacea.
### Procedures[edit]
Incision and drainage is performed if resolution does not begin in the next 48 hours after warm compresses are started. Medical professionals will sometimes lance a particularly persistent or irritating stye with a needle to accelerate its draining.[22]
Surgery is the last resort in stye treatment. Styes that do not respond to any type of therapies are usually surgically removed. Stye surgery is performed by an ophthalmologist, and generally under local anesthesia. The procedure consists of making a small incision on the inner or outer surface of the eyelid, depending if the stye is pointing externally or not. After the incision is made, the pus is drained out of the gland, and very small sutures are used to close the lesion. Sometimes the removed stye is sent for a histopathological examination to investigate possibility of skin cancer.
### Alternative medicine[edit]
A 2017 Cochrane review found low-certainty evidence that acupuncture helps in hordeolum compared with antibiotics or warm compresses.[23] There was also low-certainty evidence that acupuncture plus usual treatment may increase the chance of hordeolum getting better, though they could not rule out placebo or observer effect, since the studies reviewed either had no positive control, were not blinded, or both.[23]
## Prognosis[edit]
Although styes are harmless in most cases and complications are very rare, styes often recur. They do not cause intraocular damage, meaning they do not affect the eye. Styes normally heal on their own by rupturing within a few days to a week causing the relief of symptoms, but if it does not improve or it worsens within two weeks, a doctor's opinion should be sought. Few people require surgery as part of stye treatment. With adequate treatment, styes tend to heal quickly and without complications.
The prognosis is better if one does not attempt to squeeze or puncture the stye, as infection may spread to adjacent tissues. Also, patients are recommended to call a doctor if they encounter problems with vision, the eyelid bump becomes very painful, the stye bleeds or reoccurs, or the eyelid or eyes becomes red.[24]
## Etymology[edit]
The word stye (first recorded in the 17th century) is probably a back-formation from styany (first recorded in the 15th century),[25] which in turn comes from styan plus eye,[26] the former of which in turn comes from the old English stīġend, meaning "riser", from the verb stīġan, "to rise" (in Old English G is often a Y sound). The older form styan is still used in Ulster Scots today.
The homonym sty found in the combination pigsty has a slightly different origin, namely it comes from the Old English stī-fearh—fearh (farrow) is the Old English word for "pig"—where stig meant "hall" (cf. steward), possibly an early Old Norse loanword, which could be cognate with the word stīġan above.[27]
The synonymous late Latin expression is hordeolum a modulation of the word hordeolus simply related to hordeum ("barley"), after its resemblance to a barleycorn. In Czech, a sty is called ječné zrno (from ječmen "barley" and zrno "seed or grain"); in German, it is called Gerstenkorn (barleycorn).
## See also[edit]
* Boil
## References[edit]
1. ^ a b c "Hordeolum (Stye)". PubMed Health. Archived from the original on 8 September 2017. Retrieved 14 October 2016.
2. ^ a b Ferri, Fred F. (2016). Ferri's Clinical Advisor 2017: 5 Books in 1. Elsevier Health Sciences. p. 1219. ISBN 9780323448383. Archived from the original on 2016-10-18.
3. ^ a b c d e f g Lindsley K, Nichols JJ, Dickersin K (2017). "Non-surgical interventions for acute internal hordeolum". Cochrane Database Syst Rev. 1: CD007742. doi:10.1002/14651858.CD007742.pub4. PMC 5370090. PMID 28068454.
4. ^ a b c "Eyelid Disorders Chalazion & Stye". NEI. 4 May 2010. Archived from the original on 18 October 2016. Retrieved 14 October 2016.
5. ^ a b c d e Carlisle, RT; Digiovanni, J (15 July 2015). "Differential Diagnosis of the Swollen Red Eyelid". American Family Physician. 92 (2): 106–12. PMID 26176369.
6. ^ a b c d Deibel, JP; Cowling, K (May 2013). "Ocular inflammation and infection". Emergency Medicine Clinics of North America. 31 (2): 387–97. doi:10.1016/j.emc.2013.01.006. PMID 23601478.
7. ^ "What are the signs and symptoms of a sty?". Archived from the original on 2010-04-07. Retrieved 2010-04-06.
8. ^ "Stye Symptoms". Archived from the original on 2010-04-06. Retrieved 2010-04-06.
9. ^ "Symptoms". Archived from the original on 2010-03-07. Retrieved 2010-04-06.
10. ^ "Hordeolum and Stye: Follow-up". Archived from the original on 2010-04-09. Retrieved 2010-04-06.
11. ^ "What is the prognosis (outcome) of a sty?". Archived from the original on 2010-04-12. Retrieved 2010-04-06.
12. ^ "NIH - StatPearls - Stye".
13. ^ Tamparo, Carol; Lewis, Marcia (2011). Diseases of the Human Body. Philadelphia, PA: F.A Davis Company. p. 504. ISBN 978-0-8036-2505-1.
14. ^ "Prevention". Archived from the original on 2010-04-10. Retrieved 2010-04-06.
15. ^ "VisionWeb". Archived from the original on September 9, 2017.
16. ^ "BBC - Health - Ask the doctor - Styes". Archived from the original on February 1, 2010.
17. ^ "Merck Manual - Treat Your Sty".
18. ^ "Medical Treatment". Archived from the original on 2010-04-11. Retrieved 2010-04-06.
19. ^ a b "Merck Manual - Chalazion and Stye (Hordeolum)".
20. ^ "Medscape: Medscape Access". Emedicine.com. 2018-11-19. Archived from the original on 2008-08-04.
21. ^ eMedicine - Periorbital Infections : Article by R Gentry Wilkerson, MD. Archived 2007-04-03 at the Wayback Machine
22. ^ Sty (Stye, Hordeolum) Causes, Infection Symptoms and Treatment by MedicineNet.com Archived 2007-05-20 at the Wayback Machine
23. ^ a b Cheng K, Law A, Guo M, Wieldand LS, Shen X, Lao L (2017). "Acupuncture for acute hordeolum". Cochrane Database Syst Rev. 2: CD011075. doi:10.1002/14651858.CD011075.pub2. PMC 5378315. PMID 28181687.
24. ^ "Eyelid bump". Archived from the original on 2010-04-10. Retrieved 2010-04-06.
25. ^ sty, n.4: "sty". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
26. ^ "styan". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
27. ^ sty, n.3: "sty". Oxford English Dictionary (Online ed.). Oxford University Press. (Subscription or participating institution membership required.)
## External links[edit]
Classification
D
* ICD-10: H00.0
* ICD-9-CM: 373.11
* MeSH: D006726
* DiseasesDB: 12583
External resources
* MedlinePlus: 001009
* eMedicine: emerg/755
* Merck Manual
* "NIH - StatPearls - Stye".
Look up stye in Wiktionary, the free dictionary.
Wikimedia Commons has media related to Stye.
* v
* t
* e
* Diseases of the human eye
Adnexa
Eyelid
Inflammation
* Stye
* Chalazion
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palsies
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Other strabismus
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Anopsia
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subjective
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Pupil
* Anisocoria
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* Miosis
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* Cycloplegia
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Other
* Nystagmus
* Childhood blindness
Infections
* Trachoma
* Onchocerciasis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Stye | c0019917 | 3,610 | wikipedia | https://en.wikipedia.org/wiki/Stye | 2021-01-18T18:47:35 | {"mesh": ["D006726"], "umls": ["C0019917", "C4280376"], "icd-9": ["373.11"], "wikidata": ["Q202173"]} |
Ring chromosome 20 is a chromosome abnormality that affects the development and function of the brain. People with ring chromosome 20 often have recurrent seizures or epilepsy. Other symptoms might include intellectual disability, behavioral difficulties, growth delay, short stature, a small head (microcephaly), and characteristic facial features. Ring chromosome 20 is caused by an abnormal chromosome known as a ring chromosome 20 or r(20). A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and its broken ends fuse together. Ring chromosome 20 is usually not inherited. It almost always occurs by chance during the formation of reproductive cells (eggs or sperm) or in early embryonic development. Treatment for ring chromosome 20 is focused on management of seizures and accommodations for learning.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Ring chromosome 20 | c2930886 | 3,611 | gard | https://rarediseases.info.nih.gov/diseases/1334/ring-chromosome-20 | 2021-01-18T17:57:53 | {"mesh": ["C535369"], "umls": ["C2930886"], "orphanet": ["1444"], "synonyms": ["Chromosome 20 ring", "Ring 20", "R20", "Ring chromosome 20 syndrome"]} |
Isolated brachycephaly is a relatively frequent nonsyndromic craniosynostosis consisting of premature fusion of both coronal sutures leading to skull deformity with a broad flat forehead and palpable coronal ridges.
## Epidemiology
Incidence at birth is in the range of 1/20,000.
## Clinical description
The skull deformity is characterized by a short anteroposterior diameter with a compensatory increase in bitemporal width. Supraorbital recession and exorbitism may also be present. Brachycephaly may be associated with facial anomalies (midface hypoplasia, slight hypertelorism and bulging temporal fossae). Increased intracranial pressure (ICP) is frequent and may lead to intellectual deficit if left untreated. In adults, elevated ICP is associated with bony defects in the absence of treatment.
## Etiology
The extent to which nonsyndromic brachycephaly is genetically determined is still uncertain. Although the majority of cases are sporadic, familial forms (accounting for 14% of all cases) have been reported, with dominant inheritance in around 10% of cases. In addition, recurrent (paternally inherited) P250R mutations in fibroblast growth factor receptor 3 (FGFR3; 4p16.3) were identified in 74% of familial cases, as well as in 17% of sporadic cases. Among patients carrying the P250R mutation, females are more severely and more frequently affected than males (female to male ratio of 2:1) and mild hearing impairment is common. Minor radiologic anomalies including brachydactyly or fusion of metacarpal bones may occur in some FGFR3 mutation carriers. A mutation in the TWIST 1 gene (7p21) has been reported recently in a single case of isolated bicoronal synostosis, but a genetic origin has not been confirmed for most remaining cases. Several other determinants might be involved including mechanical constraints during pregnancy and after birth.
## Diagnostic methods
Diagnosis is based on clinical examination, radiologic studies, and 3D CT scans and/or MRI of the skull. Since postoperative morphological and functional outcomes appear to be better in non-carriers of the FGFR3 mutation, molecular screening is recommended for all families with nonsyndromic forms of brachycephaly.
## Differential diagnosis
Clinical distinction between syndromic and nonsyndromic forms brachycephaly is often difficult owing to phenotypic variability in patients carrying the P250R mutation. Although the cranial appearance of some patients might be reminiscent of the Saethre-Chotzen or Pfeiffer syndromes (see these terms), the absence of obvious hand and/or feet anomalies is a hallmark of nonsyndromic brachycephalic patients. Marked bulging of temporal fossae, seen mainly in female carriers of the FGFR3 mutation, might be instructive for differential diagnosis.
## Management and treatment
Cranial vault reconstructive surgery is the main treatment to improve skull shape and increase intracranial volume. This usually results in reduced ICP. Early identification of hearing loss allows timely intervention when required.
## Prognosis
The intellectual outcome of patients after cranial expansion surgery is usually good. However, patients carrying the FGFR3 mutation are five times more likely to require a second operation and show a poorer post surgical outcome than non-carriers.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Isolated brachycephaly | c0221356 | 3,612 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35099 | 2021-01-23T17:40:18 | {"mesh": ["D003398"], "omim": ["123100", "615314", "616602"], "umls": ["C0221356"], "icd-10": ["Q75.0"], "synonyms": ["Non-syndromic bicoronal synostosis"]} |
Multiple mitochondrial dysfunctions syndrome (MMDS) is a severe condition that affects the energy-producing structures of cells (called the mitochondria). Signs and symptoms of this condition generally develop early in life and may include encephalopathy, hypotonia (poor muscle tone), seizures, developmental delay, failure to thrive, lactic acidosis and a variety of other health problems. Due to the severity of the condition, most affected babies do not live past infancy. MMDS can be caused by changes (mutations) in the NFU1 gene or the BOLA3 gene. In these cases, the condition is inherited in an autosomal recessive manner. Treatment is based on the signs and symptoms present in each person.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Multiple mitochondrial dysfunctions syndrome | c3276432 | 3,613 | gard | https://rarediseases.info.nih.gov/diseases/12632/multiple-mitochondrial-dysfunctions-syndrome | 2021-01-18T17:58:54 | {"omim": ["605711", "614299", "615330", "616370"], "orphanet": ["289573"], "synonyms": ["Fatal multiple mitochondrial dysfunctions syndrome", "Fatal multiple mitochondrial dysfunction syndrome"]} |
Kasabach-Merritt syndrome (KMS), also known as hemangioma-thrombocytopenia syndrome, is a rare disorder characterized by profound thrombocytopenia, microangiopathic hemolytic anemia, and subsequent consumptive coagulopathy in association with vascular tumors, particularly kaposiform hemangioendothelioma or tufted angioma.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Kasabach-Merritt syndrome | c0221025 | 3,614 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2330 | 2021-01-23T18:34:48 | {"gard": ["70"], "mesh": ["D059885"], "omim": ["141000"], "umls": ["C0221025"], "icd-10": ["D18.0"], "synonyms": ["Hemangioma-thrombocytopenia syndrome"]} |
Muscle beta-enolase deficiency is a glycolysis disorder reported in one patient to date and characterized clinically by exercise intolerance and myalgia due to severe enolase deficiency in muscle.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Glycogen storage disease due to muscle beta-enolase deficiency | c2752027 | 3,615 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99849 | 2021-01-23T18:31:37 | {"gard": ["2125"], "mesh": ["C567861"], "omim": ["612932"], "umls": ["C2752027"], "icd-10": ["E74.0"], "synonyms": ["GSD due to muscle beta-enolase deficiency", "GSDXIII", "Glycogenosis due to muscle beta-enolase deficiency", "Glycogenosis type 13", "Muscle enolase deficiency", "Muscular enolase deficiency"]} |
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (January 2014)
Odynorgasmia, or painful ejaculation, is a physical syndrome described by pain or burning sensation of the urethra or perineum during or following ejaculation. Causes include infections associated with urethritis, prostatitis, epididymitis, as well as use of anti-depressants.[1][2]
## References[edit]
1. ^ Richard Balon, R. Taylor Segraves, Handbook of sexual dysfunction, Informa Healthcare; 1 edition (April 14, 2005), pg 241
2. ^ Donnellan P, Breathnach O, Crown JP (April 2001). "Odynorgasmia". Scandinavian Journal of Urology and Nephrology. 35 (2): 158. doi:10.1080/003655901750170687. PMID 11411663.
This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Odynorgasmia | c0278107 | 3,616 | wikipedia | https://en.wikipedia.org/wiki/Odynorgasmia | 2021-01-18T19:01:36 | {"umls": ["C0278107"], "wikidata": ["Q7078393"]} |
## Clinical Features
Rajab et al. (2003) reported 3 patients, including 2 sibs, with congenital generalized lipodystrophy, sensorineural deafness, low birth weight, short stature, delayed cognitive development, and progressive bone changes characterized by overtubulation and rarefaction of long bones with dense metaphyseal striations occurring in adolescence. No abnormalities of lipid or carbohydrate metabolism, hepatosplenomegaly, acanthosis nigricans, or hirsutism were found.
Inheritance
Rajab et al. (2003) suggested that the occurrence of this disorder in sibs born to consanguineous parents and the observation of a third patient from the same Omani tribal unit suggested autosomal recessive inheritance.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature Weight \- Low birth weight \- Thin body habitus Other \- Failure to thrive \- Intrauterine growth retardation HEAD & NECK Face \- Progeroid facial appearance (onset childhood) \- Maxillary hypoplasia Ears \- Sensorineural hearing loss (onset early childhood) Eyes \- Deep-set eyes CHEST External Features \- Long thorax SKELETAL \- Progressive osteopenia \- Delayed bone age Pelvis \- Short femoral necks Limbs \- Thin limbs with prominent joints \- Cubitus valgus \- Genua valgum \- Slender long bones with narrow diaphyses \- Dense longitudinal metaphyseal striations (distal femur, radius, and ulna) Hands \- Disharmonious carpal bone SKIN, NAILS, & HAIR Skin \- Sparse axillary and facial hair MUSCLE, SOFT TISSUES \- Congenital generalized lipodystrophy NEUROLOGIC Central Nervous System \- Mental retardation \- Seizures ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| LIPODYSTROPHY, GENERALIZED, WITH MENTAL RETARDATION, DEAFNESS, SHORT STATURE, AND SLENDER BONES | c1842465 | 3,617 | omim | https://www.omim.org/entry/608154 | 2019-09-22T16:08:13 | {"mesh": ["C564283"], "omim": ["608154"], "orphanet": ["50811"]} |
## Clinical Features
Chitty et al. (1996) described 2 brothers, born of first-cousin parents, with retarded growth, moderate mental retardation, sensorineural deafness, bilateral obstruction of lacrimal ducts, inguinal and umbilical hernias, and femoral epiphyseal dysplasia, predominantly on the left (capital femoral epiphysis was small and fragmented in one brother and virtually absent in the other). Chitty et al. (1996) proposed that this complex is a distinct syndrome with autosomal recessive inheritance. Three brothers described by Pfeiffer et al. (1973) had a similar complex of abnormalities (see 226950), but their femoral defects were symmetrical, they had myopia, and they did not have lacrimal duct obstruction or hernias.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Triangular face \- Pointed chin Ears \- Deafness, sensorineural Eyes \- Lacrimal duct obstruction, bilateral ABDOMEN External Features \- Inguinal hernia \- Umbilical hernia SKELETAL Limbs \- Femoral epiphyseal dysplasia NEUROLOGIC Central Nervous System \- Mental retardation, moderate ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GROWTH RETARDATION, DEAFNESS, FEMORAL EPIPHYSEAL DYSPLASIA, AND LACRIMAL DUCT OBSTRUCTION | c1832438 | 3,618 | omim | https://www.omim.org/entry/601351 | 2019-09-22T16:14:59 | {"mesh": ["C535928"], "omim": ["601351"], "orphanet": ["3218"]} |
Pulmonary valve stenosis
Other namesValvular pulmonary stenosis[1]
SpecialtyCardiology
SymptomsCyanosis, diziness[2]
CausesCongenital (most often)[3]
Diagnostic methodEchocardiogram, Ultrasound[4]
TreatmentValve replacement or surgical repair
Pulmonary valve stenosis (PVS) is a heart valve disorder. Blood going from the heart to the lungs goes through the pulmonary valve, whose purpose is to prevent blood from flowing back to the heart. In pulmonary valve stenosis this opening is too narrow, leading to a reduction of flow of blood to the lungs.[1][5]
While the most common cause of pulmonary valve stenosis is congenital heart disease, it may also be due to a malignant carcinoid tumor. Both stenosis of the pulmonary artery and pulmonary valve stenosis are forms of pulmonic stenosis (nonvalvular and valvular, respectively)[6] but pulmonary valve stenosis accounts for 80% of pulmonic stenosis. PVS was the key finding that led Jacqueline Noonan to identify the syndrome now called Noonan syndrome.
## Contents
* 1 Symptoms and signs
* 2 Cause
* 3 Pathophysiology
* 4 Diagnosis
* 5 Treatment
* 6 Epidemiology
* 7 References
* 8 Further reading
* 9 External links
## Symptoms and signs[edit]
Cynosis
Among some of the symptoms consistent with pulmonary valve stenosis are the following:[2]
* Heart murmur
* Cyanosis
* Dyspnea
* Dizziness
* Upper thorax pain
* Developmental disorders
## Cause[edit]
In regards to the cause of pulmonary valve stenosis a very high percentage are congenital, the right ventricular flow is hindered (or obstructed by this). The cause in turn is divided into: valvular, external and intrinsic (when it is acquired).[3]
## Pathophysiology[edit]
The pathophysiology of pulmonary valve stenosis consists of the valve leaflets becoming too thick (therefore not separate one from another), which can cause high pulmonary pressure, and pulmonary hypertension. This however, does not mean the cause is always congenital.[7]
The left ventricle can be changed physically, these changes are a direct result of right ventricular hypertrophy. Once the obstruction is subdued, it (the left ventricle) can return to normal.[8]
## Diagnosis[edit]
Play media
Pulmonary valve stenosis-Echocardiogram
The diagnosis of pulmonary valve stenosis can be achieved via echocardiogram, as well as a variety of other means among them are: ultrasound, in which images of the heart chambers in utero where the tricuspid valve has thickening (or due to Fallot's tetralogy, Noonan's syndrome, and other congenital defects) and in infancy auscultation of the heart can reveal identification of a murmur.[4]
Some other conditions to contemplate (in diagnosis of pulmonic valvular stenosis) are the following:[2]
* Infundibular stenosis
* Supravalvular pulmonary stenosis
* Dysplastic pulmonic valve stenosis
## Treatment[edit]
In terms of treatment for pulmonary valve stenosis, valve replacement or surgical repair (depending upon whether the stenosis is in the valve or vessel) may be indicated. If the valve stenosis is of congenital origin, balloon valvuloplasty is another option, depending on the case. Valves made from animal or human tissue (are used for valve replacement), in adults metal valves can be used.[9][10]
## Epidemiology[edit]
The epidemiology of pulmonary valve stenosis can be summed up by the congenital aspect which is the majority of cases, in broad terms PVS is rare in the general population.[4]
## References[edit]
1. ^ a b "Pulmonary valve stenosis: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Retrieved 2015-11-18.
2. ^ a b c "Pulmonic Valvular Stenosis Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 2015-11-18.
3. ^ a b Wang, Andrew; Bashore, Thomas M. (2010-01-14). Valvular Heart Disease. Springer Science & Business Media. p. 266. ISBN 9781597454117.
4. ^ a b c "Pulmonary Valve Disease. About Pulmonary valve disease | Patient". Patient. Retrieved 2015-11-18.
5. ^ Choices, NHS. "Congenital heart disease - Types - NHS Choices". www.nhs.uk. Retrieved 2015-11-18.
6. ^ Ren, XM; et al. (2014-12-23), "Pulmonic stenosis", Medscape.
7. ^ Levine, Shel; Coyne, Brian J.; Colvin, Lisa Cooper (2015-02-13). Clinical Exercise Electrocardiography. Jones & Bartlett Publishers. p. 14. ISBN 9781284034202.
8. ^ "Valvar Pulmonary Stenosis: Background, Pathophysiology, Epidemiology". 2018-06-07. Cite journal requires `|journal=` (help)
9. ^ Choices, NHS. "Congenital heart disease - Treatment - NHS Choices". www.nhs.uk. Retrieved 2015-11-18.
10. ^ "Balloon dilatation of pulmonary valve stenosis | Guidance and guidelines | NICE". www.nice.org.uk. Retrieved 2015-11-18.
## Further reading[edit]
* Ladusans, E J; Qureshi, S A; Parsons, J M; Arab, S; Baker, E J; Tynan, M (1990-06-01). "Balloon dilatation of critical stenosis of the pulmonary valve in neonates". British Heart Journal. 63 (6): 362–367. doi:10.1136/hrt.63.6.362. ISSN 0007-0769. PMC 1024522. PMID 2375899.
* Crocetti, Michael; Barone, Michael A.; Oski, Frank A. (2004-01-01). Oski's Essential Pediatrics. Lippincott Williams & Wilkins. ISBN 9780781737708.
## External links[edit]
* Overview at American Heart Association
Classification
D
* ICD-10: I37.0, I37.2, Q22.1
* ICD-9-CM: 424.3, 746.02
* OMIM: 265500
* MeSH: D011666
External resources
* MedlinePlus: 001096
* eMedicine: emerg/491 [1]
Scholia has a topic profile for Pulmonary valve stenosis.
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
* v
* t
* e
Congenital heart defects
Heart septal defect
Aortopulmonary septal defect
* Double outlet right ventricle
* Taussig–Bing syndrome
* Transposition of the great vessels
* dextro
* levo
* Persistent truncus arteriosus
* Aortopulmonary window
Atrial septal defect
* Sinus venosus atrial septal defect
* Lutembacher's syndrome
Ventricular septal defect
* Tetralogy of Fallot
Atrioventricular septal defect
* Ostium primum
Consequences
* Cardiac shunt
* Cyanotic heart disease
* Eisenmenger syndrome
Valvular heart disease
Right
* pulmonary valves
* stenosis
* insufficiency
* absence
* tricuspid valves
* stenosis
* atresia
* Ebstein's anomaly
Left
* aortic valves
* stenosis
* insufficiency
* bicuspid
* mitral valves
* stenosis
* regurgitation
Other
* Underdeveloped heart chambers
* right
* left
* Uhl anomaly
* Dextrocardia
* Levocardia
* Cor triatriatum
* Crisscross heart
* Brugada syndrome
* Coronary artery anomaly
* Anomalous aortic origin of a coronary artery
* Ventricular inversion
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pulmonary valve stenosis | c0034089 | 3,619 | wikipedia | https://en.wikipedia.org/wiki/Pulmonary_valve_stenosis | 2021-01-18T19:01:04 | {"gard": ["4596"], "mesh": ["D011666"], "umls": ["C0034089"], "icd-9": ["424.3", "746.02"], "icd-10": ["I37.0", "I37.2", "Q22.1"], "orphanet": ["99054"], "wikidata": ["Q579527"]} |
## Description
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004).
For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700.
Clinical Features
Ma et al. (2010) studied 11 affected individuals from a 4-generation Chinese family from Zhejiang province segregating autosomal dominant high myopia. The average age at diagnosis of myopia was 6.9 years (range, 4 to 11 years). The average spherical component refractive error for the affected individuals was -11.59 +/- 5.26 diopters (D) (range, -6.5 to -26 D). Mean axial length in highly myopic individuals was 29.17 +/- 1.50 mm (range, 26.80 to 31.42 mm) compared to 23.59 +/- 1.04 mm (range, 22.03 to 25.72 mm) in non-highly myopic family members. Ophthalmologic examination excluded known ocular diseases associated with myopia, including keratoconus (see 148300), spherophakia, ectopia lentis (see 129600), retinal dystrophy (see 268000), and optic atrophy (see 165500). Males and females were equally affected.
Mapping
In a 4-generation Chinese family segregating autosomal dominant high myopia, Ma et al. (2010) excluded known syndromic myopia loci, and linkage to known loci for nonsyndromic autosomal dominant high myopia was insignificant or suggestive only. Genomewide screening yielded a 2-point lod score of 3.02 at marker D5S419. Fine mapping with 13 flanking markers resulted in a significant lod score of 3.71 at marker D5S502 (theta = 0.0) on chromosome 5p15.1-p13.3. Recombination events narrowed the critical region to an approximately 11.69-cM (14.14-Mb) interval between D5S2096 and D5S1986. Ma et al. (2010) stated that the critical region identified in this family did not overlap with the locus previously found in 3 Hong Kong Chinese pedigrees with high myopia (MYP16; 612554) on chromosome 5p15.33-p15.2.
Molecular Genetics
In a 4-generation Chinese family segregating autosomal dominant high myopia mapping to chromosome 5p15.1-p13.3, Ma et al. (2010) analyzed 6 candidate genes, including CDH6 (603007), CDH10 (604555), CDH12 (600562), PDZD2 (610697), and GOLPH3 (612207), but did not identify any disease-causing mutation.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- High myopia ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| MYOPIA 19, AUTOSOMAL DOMINANT | c3151410 | 3,620 | omim | https://www.omim.org/entry/613969 | 2019-09-22T15:56:56 | {"omim": ["613969"]} |
Type of food allergy caused by peanuts
Peanut allergy
A peanut allergy warning
SpecialtyEmergency medicine
SymptomsItchiness, hives, swelling, eczema, sneezing, asthma attack, abdominal pain, drop in blood pressure, diarrhea, cardiac arrest[1]
CausesType I hypersensitivity[2]
Risk factorsChildhood in developed countries[3][4]
Diagnostic methodMedical history and physical examination by an approved doctor[2][5]
Differential diagnosisTree nut allergy
PreventionProper early introduction to peanuts and their products during pregnancy and infancy[6][3][7][8]
TreatmentEpinephrine[2]
Antihistamines (mild)[9]
Frequency0.6% (US)[10]
1.5%-3.0% (Western World)[11]
Peanut allergy is a type of food allergy to peanuts. It is different from tree nut allergies, with peanuts being legumes and not true nuts. Physical symptoms of allergic reaction can include itchiness, hives, swelling, eczema, sneezing, asthma attack, abdominal pain, drop in blood pressure, diarrhea, and cardiac arrest.[1] Anaphylaxis may occur.[1] Those with a history of asthma are more likely to be severely affected.[1]
It is due to a type I hypersensitivity reaction of the immune system in susceptible individuals.[2] The allergy is recognized "as one of the most severe food allergies due to its prevalence, persistency, and potential severity of allergic reaction."[1]
Prevention may be partly achieved through early introduction of peanuts to the diets of pregnant women and babies.[8][6] It is recommended that babies at high risk be given peanut products in areas where medical care is available as early as 4 months of age.[12] The principal treatment for anaphylaxis is the injection of epinephrine.[2]
In the United States, peanut allergy is present in 0.6% of the population.[10][13] Among children in the Western world, rates are between 1.5% and 3% and have increased over time.[11] It is a common cause of food-related fatal and near-fatal allergic reactions.[14]
## Contents
* 1 Signs and symptoms
* 1.1 Tree nuts and soy
* 2 Cause
* 2.1 Timing of exposure
* 2.2 Diet during pregnancy
* 2.3 Routes of exposure
* 3 Pathophysiology
* 4 Diagnosis
* 4.1 Skin prick testing
* 4.2 Oral food challenge
* 5 Prevention
* 6 Treatment
* 6.1 Immunotherapy
* 7 Prognosis
* 8 Epidemiology
* 9 Society and culture
* 9.1 Labeling
* 9.1.1 Ingredients intentionally added
* 9.1.2 Trace amounts as a result of cross-contamination
* 10 See also
* 11 References
* 12 Further reading
* 13 External links
## Signs and symptoms[edit]
Most symptoms of peanut allergy are related to the action of immunoglobulin E (IgE)[15] and other anaphylatoxins which act to release histamine and other mediator substances from mast cells (degranulation). In addition to other effects, histamine induces vasodilation of arterioles and constriction of bronchioles in the lungs, also known as bronchospasm. Symptoms can also include mild itchiness, hives, angioedema, facial swelling, rhinitis, vomiting, diarrhea, acute abdominal pain, exacerbation of atopic eczema, asthma, and cardiac arrest.[1] Anaphylaxis may occur.[1][16]
### Tree nuts and soy[edit]
People with confirmed peanut allergy may have cross-reactivity to tree nut, soy, and other legumes, such as peas and lentils and lupinus.[17][18][19][20] The cause of cross-reactivity results from similarity in the structures of storage proteins between the food sources.[17] Allergenic proteins are grouped by protein families: cupins, prolamins, profilin and others. Peanuts and soybeans have proteins in the cupin, prolamin, and profilin families, while lentils contain cupin proteins.[17] Reviews of human clinical trials report that 6–40% of people with a confirmed peanut allergy will have allergic symptoms when challenged with tree nuts or legumes.[19][21]
## Cause[edit]
The cause of peanut allergy is unclear and at least 11 peanut allergens have been described.[22][23] The condition is associated with several specific proteins categorized according to four common food allergy superfamilies: Cupin (Ara h 1), Prolamin (Ara h 2, 6, 7, 9), Profilin (Ara h 5), and Bet v-1-related proteins (Ara h 8).[24] Among these peanut allergens, Ara h 1, Ara h 2, Ara h 3 and Ara h 6 are considered to be major allergens which means that they trigger an immunological response in more than 50% of the allergic population.[24] These peanut allergens mediate an immune response via release of Immunoglobulin E (IgE) antibody as part of the allergic reaction.[24]
Some of the peanut allergens can undergo enzymatic and non-enzymatic modifications which makes them more likely to bind to ligands on antigen-presenting cells. Ara h 1 can undergo glycosylation modifications which have been shown to induce immunomodulatory responses; it stimulates lectin receptors MR and DC-SIGN on dendritic cells which further propagate cytokines and bias the immune system towards a Th2 type response.[24] Peanut proteins that undergo non-enzymatic changes through Maillard reactions when cooked or exposed to room temperature have an increase in AGE modifications on their structure.[24] These changes have been shown to stimulate RAGE receptors and SR-AI/II on dendritic cells and thus lead to an increase in IL-4 and IL-5-releasing Th2 cells.
Peanut allergies are uncommon in children of undeveloped countries[3] where peanut products have been used to relieve malnutrition.[25] The hygiene hypothesis proposes that the relatively low incidence of childhood peanut allergies in undeveloped countries is a result of exposure to diverse food sources early in life, increasing immune capability, whereas food selection by children in developed countries is more limited, reducing immune capability.[3][4] A possibility of cross-reaction to soy was dismissed by an analysis finding no linkage to consumption of soy protein, and indicated that appearance of any linkage is likely due to preference to using soy milk among families with known milk allergies.[26]
### Timing of exposure[edit]
In infants with a family history of peanut allergy, consuming peanut proteins at 4 to 11 months old has been shown to reduce the risk of developing an allergic response by 11-25% [27] From these results, the American Academy of Pediatrics rescinded their recommendation to delay exposure to peanuts in children, also stating there is no reason to avoid peanuts during pregnancy or breastfeeding.[28][29]
### Diet during pregnancy[edit]
There is conflicting evidence on whether maternal diet during pregnancy has any effect on development of allergies due to a lack of good studies.[30] A 2010 systematic review of clinical research indicated that there is insufficient evidence for whether maternal peanut exposure, or early consumption of peanuts by children, affects sensitivity for peanut allergy.[31]
### Routes of exposure[edit]
Peanuts
While the most obvious route for an allergic exposure is unintentional ingestion, some reactions are possible through external exposure. Peanut allergies are much more common in infants who had oozing and crusted skin rashes as infants.[32] Sensitive children may react via ingestion, inhalation, or skin contact to peanut allergens which have persistence in the environment, possibly lasting over months.[33]
Airborne particles in a farm- or factory-scale shelling or crushing environment, or from cooking, can produce respiratory effects in exposed allergic individuals.[34] Empirical testing has discredited some reports of this type and shown some to be exaggerated. Residue on surfaces has been known to cause minor skin rashes, though not anaphylaxis. In The Peanut Allergy Answer Book, Harvard pediatrician Michael Young characterized this secondary contact risk to allergic individuals as rare and limited to minor symptoms.[34] Some reactions have been noted to be psychosomatic in nature, the result of conditioning, and belief rather than a true chemical reaction. Blinded, placebo-controlled studies were unable to produce any reactions using the odor of peanut butter or its mere proximity.[34]
## Pathophysiology[edit]
The allergy arises due to dendritic cells recognizing peanut allergens as foreign pathogens.[35] They present the antigens on MHC class II receptors and these antigens are recognized by cell receptors on T cells. The contact along with the release of the cytokine IL-4 induces their differentiation into CD4+ Th2 cells.[35] The Th2 cells proliferate and release pro-inflammatory cytokines, such as IL-4, IL-5, and IL-13, which can be bound to receptors on undifferentiated B cells or B cells of the IgM subtype.[35] The receptor-cytokine binding causes their differentiation into IgE which can then be bound onto FcεRI on mast cells, eosinophils and basophils.[35] This elicits degranulation of the aforementioned cells which release potent cytokines and chemokines, thus triggering inflammation and causing the symptoms characteristic of allergy.[35]
## Diagnosis[edit]
Diagnosis of food allergies, including peanut allergy, begins with a medical history and physical examination.[2][5] National Institute of Allergy and Infectious Diseases guidelines recommend that parent and patient reports of food allergy be confirmed by a doctor because "multiple studies demonstrate 50% to 90% of presumed food allergies are not allergies."[5]
### Skin prick testing[edit]
Skin prick tests can be used to confirm specific food allergies.[1][2][5] Skin prick tests are designed to identify specific IgE bound to cutaneous mast cells.[1] During the test, a glycerinated allergen extract drop is placed on the patient's skin.[2] The patient's skin is then pricked through the drop.[2] This procedure is repeated with two controls: a histamine drop designed to elicit an allergic response, and a saline drop designed to elicit no allergic response.[2] The wheal that develops from the glycerinated extract drop is compared against the saline control.[2] A positive allergic test is one in which the extract wheal is 3mm larger than the saline wheal.[2] A positive skin prick test is about 50% accurate, so a positive skin prick test alone is not diagnostic of food allergies.[1][2][5]
### Oral food challenge[edit]
The "gold standard" of diagnostic tests is a double-blind placebo-controlled oral food challenge.[2][5] At least two weeks prior to an oral food challenge, the person is placed on an elimination diet where the suspected allergen is avoided.[36] During the oral food challenge, they are administered a full age-appropriate serving of a suspected allergen in escalating size increments.[36] They are continuously monitored for allergic reaction during the test, and the challenge is stopped and treatment administered at the first objective sign of allergic reaction.[36]
Oral food challenges pose risks.[37] In a study of 584 oral food challenges administered to 382 patients, 48% (253) of challenges resulted in allergic reactions.[37] 28% (72) of these challenges resulted in "severe" reactions, which were defined by the study as a patient having: lower respiratory symptoms; cardiovascular symptoms; or any four other, more minor, symptoms.[37] Double-blind placebo-controlled oral food challenges are also time-consuming and require close medical supervision.[2] Because of these drawbacks to the double-blind placebo-controlled oral food challenge, open food challenges are the most commonly used form of food challenge.[36] Open food challenges are those in which a patient is fed an age-appropriate serving of a suspected food allergen in its natural form.[36] The observation of objective symptoms resulting from ingestion of the food, such as vomiting or wheezing, is considered diagnostic of food allergy if the symptoms correlate with findings from the patient's medical history and laboratory testing such as the skin prick test.[5]
## Prevention[edit]
In 2017, the US National Institute of Allergy and Infectious Diseases (NIAID) published revised guidelines for lowering the risk or preventing peanut allergies by creating separate ways to assess childhood allergies and guide parents with infants at high, moderate or low risk.[13][38][7] The guidelines discussed how to introduce peanut foods to infants as early as 4 to 6 months of age, with the goal of preventing peanut allergy.[6][3][7]
For high-risk children, the guide recommended that an allergy specialist assess a child's susceptibility, possibly involving peanut allergy testing, followed by gradual introduction of peanut foods under the supervision of an allergy specialist.[6][7] Peanut allergy is confirmed only if there is a history of reactions to peanut consumption and by a positive allergy test.[7] Moderate-risk children – who display an allergic reaction to peanut products with mild to moderate eczema – are typically not assessed in a clinic, but rather have peanut foods gradually provided to them at home by their parents, beginning at around age 6 months.[6][15][7] The Learning Early About Peanut Allergy (LEAP) study supported by NIAID established that early introduction of peanut products into a child's diet can prevent – rather than only delay – the development of childhood peanut allergies, and that the effect is beneficial and lifelong.[6][15][3]
## Treatment[edit]
As of 2020, there is no cure for peanut allergy other than strict avoidance of peanuts and peanut-containing foods. Extra care is needed for food consumed at or purchased from restaurants.[2]
Total avoidance is complicated because the declaration of the presence of trace amounts of allergens in foods is not mandatory (see regulation of labelling).
### Immunotherapy[edit]
Immunotherapy involves attempts to reduce allergic sensitivity by repeated exposure to small amounts of peanut products.[39][40] Evidence as of 2019, however, has found that it increases rather than decreases the risk of serious allergies.[41] None of these are considered ready for use in people outside of carefully conducted trials.[42] A 2012 Cochrane Review concluded that more research was needed.[43] Sublingual immunotherapy involves putting gradually increasing doses of an allergy extract under a person's tongue.[42] The extract is then either spat or swallowed.[42] As of 2014, the evidence did not show that this was safe or effective.[42] Epicutaneous immunotherapy involves giving the allergen through a patch and has also been researched.[42]
In September 2014, the U.S. Food and Drug Administration (FDA) granted fast track designation, and in June 2015, granted breakthrough therapy designation to AR101 for peanut allergy in ages 4–17.[44] AR101 was studied in the PALISADE international, multicenter, randomized, double-blind, placebo-controlled study.[45][46]
In September 2019, the Allergenic Products Advisory Committee (APAC) of the Center for Biologics Evaluation and Research (CBER) voted to support the use of peanut allergen powder (Palforzia) for peanut allergy.[47][48][49] The price has not been set as of September 2019, but is proposed to be between US$3,000 and US$20,000 per year.[50]
In January 2020, peanut allergen powder was approved in the United States to mitigate allergic reactions, including anaphylaxis, that may occur with accidental exposure to peanuts.[51] Treatment with peanut allergen powder may be initiated in individuals ages four through 17 years with a confirmed diagnosis of peanut allergy and may be continued in individuals four years of age and older.[51] Those who take peanut allergen powder must continue to avoid peanuts in their diets.[51]
On 15 October 2020, the European Medicines Agency (EMA) issued a favourable opinion for a medicinal product made from defatted powder of Arachis hypogaea. This medicine will be available as an oral powder in capsules (0.5, 1, 10, 20 and 100 mg) and as an oral powder in sachets (300 mg).[52]
## Prognosis[edit]
Peanut allergies tend to resolve in childhood less often than allergies to soy, milk, egg, and wheat.[53] Accordingly, re-evaluation of peanut allergy is recommended on a yearly basis for young children with favorable previous test results, and every few years or longer for older children and adults.[53] A 2001 study showed that peanut allergy is outgrown in 22% of cases for people aged 4 to 20 years.[54]
## Epidemiology[edit]
The percentage of people with peanut allergies is 0.6% in the United States.[13] In a 2008 study, self-reported incidence of peanut allergy was estimated to affect 1.4% of children the United States, triple the 0.4% rate found in a 1997 study.[55] In England, an estimated 4,000 people are newly diagnosed with peanut allergy every year, 25,700 having been diagnosed with peanut allergy at some point in their lives.[56]
Peanut allergy is one of the most dangerous food allergies, and one of the least likely to be outgrown.[55] In Western countries, the incidence of peanut allergy is between 1-3%.[27] There has been a sudden increase in number of cases in the early 21st century.[27]
It is one of the most common causes of food-related deaths.[14] A meta-analysis found that death due to overall food-induced anaphylaxis was 1.8 per million person-years in people having food allergies, with peanut as the most common allergen.[33] However, there are opinions that the measures taken in response to the threat may be an over-reaction out of proportion to the level of danger. Media sensationalism has been blamed for anxiety outweighing reality.[57]
Frequency among adults and children is similar—around 1%—but one study showed self-reports of peanut allergy are on the rise in children in the United States.[58] The number of young children self-reporting the allergy doubled between 1997 and 2002.[59] Studies have found that self-reported rates of food allergies is higher than clinically-observed rates of food allergies.[2] The rates in self-reported incidence of the allergy, previously thought to be rare, may not be correlated with medical data confirming the self-reported incidence.[60][61]
## Society and culture[edit]
The high severity of peanut allergy reactions, as well as the increasing prevalence of peanut allergy in the Western world have led to widespread public attention. However, the perceived prevalence of food allergies in the public view is substantially higher than the actual prevalence of food allergies.[2] Because peanut allergy awareness has increased, there are impacts on the quality of life for children, their parents and their immediate caregivers.[62][63][64][65] In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 causes people to be reminded of allergy problems every time they handle a food package, and restaurants have added allergen warnings to menus. The Culinary Institute of America, a premier school for chef training, has courses in allergen-free cooking and a separate teaching kitchen.[66] School systems have protocols about what foods can be brought into the school. Despite all these precautions, people with serious allergies are aware that accidental exposure can still easily occur at other people's houses, at school or in restaurants.[67] Food fear has a significant impact on quality of life.[64][65] Finally, for children with allergies, their quality of life is also affected by actions of their peers. There is an increased occurrence of bullying, which can include threats or acts of deliberately being touched with foods they need to avoid, also having their allergen-free food deliberately contaminated.[68]
### Labeling[edit]
An example of a list of allergens in a food item
In response to the risk that certain foods pose to those with food allergies, some countries have responded by instituting labeling laws that require food products to clearly inform consumers if their products contain major allergens or byproducts of major allergens among the ingredients intentionally added to foods. Nevertheless, there are no labeling laws to mandatory declare the presence of trace amounts in the final product as a consequence of cross-contamination, except in Brazil.[69][70][71][72][73][74][75][76]
#### Ingredients intentionally added[edit]
In the United States, the Food Allergen Labeling and Consumer Protection Act of 2004 (FALCPA) requires companies to disclose on the label whether a packaged food product contains any of these eight major food allergens, added intentionally: cow's milk, peanuts, eggs, shellfish, fish, tree nuts, soy and wheat.[70] This list originated in 1999, from the World Health Organisation Codex Alimentarius Commission.[75] To meet FALCPA labeling requirements, if an ingredient is derived from one of the required-label allergens, then it must either have its "food sourced name" in parentheses, for example "Casein (milk)," or as an alternative, there must be a statement separate but adjacent to the ingredients list: "Contains milk" (and any other of the allergens with mandatory labeling).[70][72] The European Union requires listing for those eight major allergens plus molluscs, celery, mustard, lupin, sesame and sulfites.[71]
FALCPA applies to packaged foods regulated by the U.S. Food and Drug Administration (FDA), which does not include poultry, most meats, certain egg products, and most alcoholic beverages.[76] However, some meat, poultry, and egg processed products may contain allergenic ingredients. These products are regulated by the Food Safety and Inspection Service (FSIS), which requires that any ingredient be declared in the labeling only by its common or usual name. Neither the identification of the source of a specific ingredient in a parenthetical statement nor the use of statements to alert for the presence of specific ingredients, like "Contains: milk", are mandatory according to FSIS.[73][74] FALCPA also does not apply to food prepared in restaurants.[77][78] The EU Food Information for Consumers Regulation 1169/2011 – requires food businesses to provide allergy information on food sold unpackaged, for example, in catering outlets, deli counters, bakeries and sandwich bars.[79]
In the United States, there is no federal mandate to address the presence of allergens in drug products. FALCPA does not apply to medicines nor to cosmetics.[80]
#### Trace amounts as a result of cross-contamination[edit]
The value of allergen labeling other than for intentional ingredients is controversial. This concerns labeling for ingredients present unintentionally as a consequence of cross-contact or cross-contamination at any point along the food chain (during raw material transportation, storage or handling, due to shared equipment for processing and packaging, etc.).[75][76] Experts in this field propose that if allergen labeling is to be useful to consumers, and healthcare professionals who advise and treat those consumers, ideally there should be agreement on which foods require labeling, threshold quantities below which labeling may be of no purpose, and validation of allergen detection methods to test and potentially recall foods that were deliberately or inadvertently contaminated.[81][82]
Labeling regulations have been modified to provide for mandatory labeling of ingredients plus voluntary labeling, termed precautionary allergen labeling (PAL), also known as "may contain" statements, for possible, inadvertent, trace amount, cross-contamination during production.[75][83] PAL labeling can be confusing to consumers, especially as there can be many variations on the wording of the warning.[83][84] As of 2014[update] PAL is regulated only in Switzerland, Japan, Argentina, and South Africa. Argentina decided to prohibit precautionary allergen labeling since 2010, and instead puts the onus on the manufacturer to control the manufacturing process and label only those allergenic ingredients known to be in the products. South Africa does not permit the use of PAL, except when manufacturers demonstrate the potential presence of allergen due to cross-contamination through a documented risk assessment and despite adherence to Good Manufacturing Practice.[75] In Australia and New Zealand there is a recommendation that PAL be replaced by guidance from VITAL 2.0 (Vital Incidental Trace Allergen Labeling). A review identified "the eliciting dose for an allergic reaction in 1% of the population" as ED01. This threshold reference dose for foods (such as cow's milk, egg, peanut and other proteins) will provide food manufacturers with guidance for developing precautionary labeling and give consumers a better idea of might be accidentally in a food product beyond "may contain."[85][86] VITAL 2.0 was developed by the Allergen Bureau, a food industry sponsored, non-government organization.[87] The European Union has initiated a process to create labeling regulations for unintentional contamination but is not expected to publish such before 2024.[88]
In Brazil, since April 2016, the declaration of the possibility of cross-contamination is mandatory when the product does not intentionally add any allergenic food or its derivatives, but the Good Manufacturing Practices and allergen control measures adopted are not sufficient to prevent the presence of accidental trace amounts. These allergens include wheat, rye, barley, oats and their hybrids, crustaceans, eggs, fish, peanuts, soybean, milk of all species of mammalians, almonds, hazelnuts, cashew nuts, Brazil nuts, macadamia nuts, walnuts, pecan nuts, pistaches, pine nuts, and chestnuts.[69]
## See also[edit]
* Allergy (has diagrams showing involvement of different types of white blood cells)
* Food allergy (has images of hives, skin prick test and patch test)
* List of allergens (food and non-food)
* Tree nut allergy (can be cross-reactive to peanut allergy)
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81. ^ Mills EN, Valovirta E, Madsen C, et al. (2004). "Information provision for allergic consumers--where are we going with food allergen labelling?". Allergy. 59 (12): 1262–1268. doi:10.1111/j.1398-9995.2004.00720.x. PMID 15507093. S2CID 40395908.
82. ^ Taylor SL, Baumert JL (2015). "Worldwide food allergy labeling and detection of allergens in processed foods". Food Allergy: Molecular Basis and Clinical Practice. Chem Immunol Allergy. Chemical Immunology and Allergy. 101. pp. 227–234. doi:10.1159/000373910. ISBN 978-3-318-02340-4. PMID 26022883.
83. ^ a b DunnGalvin A, Chan CH, et al. (2015). "Precautionary allergen labelling: perspectives from key stakeholder groups". Allergy. 70 (9): 1039–1051. doi:10.1111/all.12614. PMID 25808296. S2CID 18362869.
84. ^ Zurzolo GA, de Courten M, Koplin J, et al. (2016). "Is advising food allergic patients to avoid food with precautionary allergen labelling out of date?". Curr Opin Allergy Clin Immunol. 16 (3): 272–277. doi:10.1097/ACI.0000000000000262. PMID 26981748. S2CID 21326926.
85. ^ Allen KJ, Remington BC, Baumert JL, et al. (2014). "Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications". J. Allergy Clin. Immunol. 133 (1): 156–164. doi:10.1016/j.jaci.2013.06.042. PMID 23987796.
86. ^ Taylor SL, Baumert JL, Kruizinga AG, et al. (2014). "Establishment of Reference Doses for residues of allergenic foods: report of the VITAL Expert Panel". Food Chem. Toxicol. 63: 9–17. doi:10.1016/j.fct.2013.10.032. PMID 24184597.
87. ^ The VITAL Program Allergen Bureau, Australia and New Zealand.
88. ^ Popping B, Diaz-Amigo C (2018). "European Regulations for Labeling Requirements for Food Allergens and Substances Causing Intolerances: History and Future". J AOAC Int. 101 (1): 2–7. doi:10.5740/jaoacint.17-0381. PMID 29202901.
## Further reading[edit]
* Leickly, Frederick E.; Kloepfer, Kirsten M.; Slaven, James E.; et al. (2018). "Peanut Allergy: An Epidemiologic Analysis of a Large Database". The Journal of Pediatrics. 192: 223–228.e1. doi:10.1016/j.jpeds.2017.09.026. ISSN 0022-3476. PMID 29246346.</ref>
## External links[edit]
Classification
D
* ICD-10: T78.0, T78.1, L23.6, L27.2, Z91.0
* ICD-9-CM: 995.61, V15.01
* MeSH: D021183
* DiseasesDB: 29154
* "Peanut allergy". Drug Information Portal. U.S. National Library of Medicine.
* v
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* e
Allergic conditions
Respiratory system
* Allergic rhinitis (hay fever)
* Asthma
* Hypersensitivity pneumonitis
* Eosinophilic pneumonia
* Eosinophilic granulomatosis with polyangiitis
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Skin
* Angioedema
* Urticaria
* Atopic dermatitis
* Allergic contact dermatitis
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* Serum sickness
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* APS1
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* Medicine portal
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Peanut allergy | c0559470 | 3,621 | wikipedia | https://en.wikipedia.org/wiki/Peanut_allergy | 2021-01-18T19:08:22 | {"mesh": ["D021183"], "umls": ["C0559470"], "icd-9": ["995.61"], "icd-10": ["T78.4"], "wikidata": ["Q7157933"]} |
Kleefstra syndrome is a disorder that involves many parts of the body. Characteristic features of Kleefstra syndrome include developmental delay and intellectual disability, severely limited or absent speech, and weak muscle tone (hypotonia). Affected individuals also have an unusually small head size (microcephaly) and a wide, short skull (brachycephaly). Distinctive facial features include eyebrows that grow together in the middle (synophrys), widely spaced eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), nostrils that open to the front rather than downward (anteverted nares), a protruding jaw (prognathism), rolled out (everted) lips, and a large tongue (macroglossia). Affected individuals may have a high birth weight and childhood obesity.
People with Kleefstra syndrome may also have structural brain abnormalities, congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections. During childhood they may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm (apathy) or unresponsiveness (catatonia).
## Frequency
The prevalence of Kleefstra syndrome is unknown. Only recently has testing become available to distinguish it from other disorders with similar features.
## Causes
Kleefstra syndrome is caused by the loss of the EHMT1 gene or by mutations that disable its function. The EHMT1 gene provides instructions for making an enzyme called euchromatic histone methyltransferase 1. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones, histone methyltransferases can turn off (suppress) the activity of certain genes, which is essential for normal development and function.
Most people with Kleefstra syndrome are missing a sequence of about 1 million DNA building blocks (base pairs) on one copy of chromosome 9 in each cell. The deletion occurs near the end of the long (q) arm of the chromosome at a location designated q34.3, a region containing the EHMT1 gene. Some affected individuals have shorter or longer deletions in the same region.
The loss of the EHMT1 gene from one copy of chromosome 9 in each cell is believed to be responsible for the characteristic features of Kleefstra syndrome in people with the 9q34.3 deletion. However, the loss of other genes in the same region may lead to additional health problems in some affected individuals.
About 25 percent of individuals with Kleefstra syndrome do not have a deletion of genetic material from chromosome 9; instead, these individuals have mutations in the EHMT1 gene. Some of these mutations change single protein building blocks (amino acids) in euchromatic histone methyltransferase 1. Others create a premature stop signal in the instructions for making the enzyme or alter the way the gene's instructions are pieced together to produce the enzyme. These changes generally result in an enzyme that is unstable and decays rapidly, or that is disabled and cannot function properly.
Either a deletion or a mutation affecting the EHMT1 gene results in a lack of functional euchromatic histone methyltransferase 1 enzyme. A lack of this enzyme impairs proper control of the activity of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kleefstra syndrome.
### Learn more about the gene and chromosome associated with Kleefstra syndrome
* EHMT1
* chromosome 9
## Inheritance Pattern
The inheritance of Kleefstra syndrome is considered to be autosomal dominant because a deletion in one copy of chromosome 9 in each cell or a mutation in one copy of the EHMT1 gene is sufficient to cause the condition. Most cases of Kleefstra syndrome are not inherited, however. The genetic change occurs most often as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family, though they can pass the disorder on to their children. Only a few people with Kleefstra syndrome have been known to reproduce.
Rarely, affected individuals inherit a chromosome 9 with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with Kleefstra syndrome who inherit an unbalanced translocation are missing genetic material from the long arm of chromosome 9.
A few individuals with Kleefstra syndrome have inherited the chromosome 9q34.3 deletion from an unaffected parent who is mosaic for the deletion. Mosaic means that an individual has the deletion in some cells (including some sperm or egg cells), but not in others.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Kleefstra syndrome | c0795833 | 3,622 | medlineplus | https://medlineplus.gov/genetics/condition/kleefstra-syndrome/ | 2021-01-27T08:25:13 | {"gard": ["8672"], "mesh": ["C563043"], "omim": ["610253"], "synonyms": []} |
Rare genetic condition involving underdeveloped eyelids
Blepharophimosis, ptosis, epicanthus inversus syndrome
Other namesBlepharophimosis types 1 and 2
18-year-old female with BPES type 1
This condition is inherited in an autosomal dominant manner.
Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is a rare disease characterized by the conditions it is named after: blepharophimosis, ptosis and epicanthus inversus. There are two types; type 1 is distinguished from type 2 by including the symptom of premature ovarian insufficiency (POI) in females, which causes menopausal symptoms and infertility in patients as young as 15 years old.[1]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Diagnosis
* 4 Treatment
* 5 Epidemiology
* 6 References
* 7 External links
## Signs and symptoms[edit]
The most prominent symptoms of BPES are horizontally narrow eyes (blepharophimosis), drooping eyelids (ptosis) and a fold of skin running from the side of the nose to the lower eyelid (epicanthus inversus). Other common symptoms include lack of an eyelid fold, an appearance of widely spaced eyes (telecanthus), low nose bridge and ear malformations (including cupping and incomplete development). Rare symptoms include microphthalmos (abnormally small eyes), tear ducts in the wrong location and a high-arched palate.[1] Type 1 BPES is distinguished by including premature ovarian insufficiency (POI) in females, which causes menopausal symptoms and infertility in patients as young as 15 years old.[1]
## Genetics[edit]
BPES is caused by a mutation in the gene FOXL2, located at 3q23 (band 23 on the long arm of chromosome 3). There are two types, caused by different mutations in this gene, but both follow an autosomal dominant pattern of inheritance.[1]
## Diagnosis[edit]
Though BPES can be suggested by the presence of blepharophimosis, ptosis and/or epicanthus inversus, it can only be definitively diagnosed by genetic testing. Other disorders that appear similar include Waardenburg syndrome and Ohdo blepharophimosis syndrome.[1]
## Treatment[edit]
The main treatment is symptomatic, since the underlying genetic defect cannot be corrected as of 2015. Symptomatic treatment is surgical.[1]
## Epidemiology[edit]
BPES is very rare: only 50–100 cases have been described. It affects slightly more males than females.[1]
## References[edit]
1. ^ a b c d e f g "Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2015-10-30.
## External links[edit]
Classification
D
* ICD-10: Q10.3
* OMIM: 110100
* MeSH: C562419
External resources
* Orphanet: 126
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Blepharophimosis, ptosis, epicanthus inversus syndrome | c0220663 | 3,623 | wikipedia | https://en.wikipedia.org/wiki/Blepharophimosis,_ptosis,_epicanthus_inversus_syndrome | 2021-01-18T18:55:24 | {"mesh": ["C562419"], "umls": ["C0220663"], "orphanet": ["126"], "wikidata": ["Q18554819"]} |
Main articles: Aphasia and Primary progressive aphasia
Progressive nonfluent aphasia (PNFA) is one of three clinical syndromes associated with frontotemporal lobar degeneration. PNFA has an insidious onset of language deficits over time as opposed to other stroke-based aphasias, which occur acutely following trauma to the brain. The specific degeneration of the frontal and temporal lobes in PNFA creates hallmark language deficits differentiating this disorder from other Alzheimer-type disorders by the initial absence of other cognitive and memory deficits. This disorder commonly has a primary effect on the left hemisphere, causing the symptomatic display of expressive language deficits (production difficulties) and sometimes may disrupt receptive abilities in comprehending grammatically complex language.[1]
## Contents
* 1 Presentation
* 2 Diagnosis
* 2.1 Classification
* 3 Management
* 4 See also
* 5 References
* 6 Further reading
## Presentation[edit]
The main clinical features are signature language progressive difficulties with speech production. There can be problems in different parts of the speech production system, hence patients can present with articulatory breakdown, phonemic breakdown (difficulties with sounds) and other problems. However, it is rare for patients to have just one of these problems and most people will present with more than one problem. Features include:
* Hesitant, effortful speech
* Apraxia of speech
* Stutter (including return of a childhood stutter)
* Anomia
* Phonemic paraphasia (sound errors in speech e.g. 'gat' for 'cat')
* Agrammatism (using the wrong tense or word order)
As the disease develops, speech quantity decreases and many patients become mute.
Cognitive domains other than language are rarely affected early on. However, as the disease progresses, other domains can be affected. Problems with writing, reading, and speech comprehension can occur, as can behavioural features similar to frontotemporal dementia.
## Diagnosis[edit]
Imaging studies have shown differing results which probably represents the heterogeneity of language problems than can occur in PNFA. However, classically atrophy of left perisylvian areas is seen. Comprehensive meta-analyses on MRI and FDG-PET studies identified alterations in the whole left frontotemporal network for phonological and syntactical processing as the most consistent finding.[2] Based on these imaging methods, progressive nonfluent aphasia can be regionally dissociated from the other subtypes of frontotemporal lobar degeneration, frontotemporal dementia and semantic dementia.
### Classification[edit]
Some confusion exists in the terminology used by different neurologists. Mesulam's original description in 1982 of progressive language problems caused by neurodegenerative disease (which he called primary progressive aphasia (PPA) [3][4] included patients with progressive nonfluent (aphasia, semantic dementia, and logopenic progressive aphasia.[5][6][7]
## Management[edit]
No cure or treatment for this condition has been found. Supportive management is helpful.
## See also[edit]
* Alzheimer's disease
* Corticobasal degeneration
* Pick's disease
## References[edit]
1. ^ M. Hunter Manasco (2014). Introduction to Neurogenic Communication Disorders. pp. 86–88. ISBN 9780323290920.
2. ^ Schroeter ML, Raczka KK, Neumann J, von Cramon DY (2007). "Towards a nosology for frontotemporal lobar degenerations – A meta-analysis involving 267 subjects". NeuroImage. 36 (3): 497–510. doi:10.1016/j.neuroimage.2007.03.024. PMID 17478101.
3. ^ Mesulam M (1982). "Slowly progressive aphasia without generalized dementia". Ann. Neurol. 11 (6): 592–8. doi:10.1002/ana.410110607. PMID 7114808.
4. ^ Mesulam MM (April 2001). "Primary progressive aphasia". Ann. Neurol. 49 (4): 425–32. doi:10.1002/ana.91. PMID 11310619.
5. ^ Gorno-Tempini ML, Hillis AE, Weintraub S, et al. (March 2011). "Classification of primary progressive aphasia and its variants". Neurology. 76 (11): 1006–14. doi:10.1212/WNL.0b013e31821103e6. PMC 3059138. PMID 21325651.
6. ^ Bonner MF, Ash S, Grossman M (November 2010). "The new classification of primary progressive aphasia into semantic, logopenic, or nonfluent/agrammatic variants". Curr Neurol Neurosci Rep. 10 (6): 484–90. doi:10.1007/s11910-010-0140-4. PMC 2963791. PMID 20809401.
7. ^ Harciarek M, Kertesz A (September 2011). "Primary progressive aphasias and their contribution to the contemporary knowledge about the brain-language relationship". Neuropsychol Rev. 21 (3): 271–87. doi:10.1007/s11065-011-9175-9. PMC 3158975. PMID 21809067.
## Further reading[edit]
* Gliebus G (March 2010). "Primary progressive aphasia: clinical, imaging, and neuropathological findings". Am J Alzheimers Dis Other Demen. 25 (2): 125–7. doi:10.1177/1533317509356691. PMID 20124255.
* Gorno-Tempini ML, Dronkers NF, Rankin KP, et al. (March 2004). "Cognition and anatomy in three variants of primary progressive aphasia". Ann. Neurol. 55 (3): 335–46. doi:10.1002/ana.10825. PMC 2362399. PMID 14991811.
* Henry ML, Gorno-Tempini ML (December 2010). "The logopenic variant of primary progressive aphasia". Curr. Opin. Neurol. 23 (6): 633–7. doi:10.1097/WCO.0b013e32833fb93e. PMC 3201824. PMID 20852419.
* Mesulam MM (October 2003). "Primary progressive aphasia—a language-based dementia". N. Engl. J. Med. 349 (16): 1535–42. doi:10.1056/NEJMra022435. PMID 14561797.
* Reilly J, Rodriguez AD, Lamy M, Neils-Strunjas J (2010). "Cognition, language, and clinical pathological features of non-Alzheimer's dementias: an overview". J Commun Disord. 43 (5): 438–52. doi:10.1016/j.jcomdis.2010.04.011. PMC 2922444. PMID 20493496.
* Rohrer JD, Knight WD, Warren JE, Fox NC, Rossor MN, Warren JD (January 2008). "Word-finding difficulty: a clinical analysis of the progressive aphasias". Brain. 131 (Pt 1): 8–38. doi:10.1093/brain/awm251. PMC 2373641. PMID 17947337.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Progressive nonfluent aphasia | c0751706 | 3,624 | wikipedia | https://en.wikipedia.org/wiki/Progressive_nonfluent_aphasia | 2021-01-18T19:04:35 | {"gard": ["10793"], "mesh": ["D057178"], "umls": ["C0751706"], "orphanet": ["100070"], "wikidata": ["Q18583"]} |
A number sign (#) is used with this entry because of evidence that short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis (SSASKS) is caused by homozygous or compound heterozygous mutation in the SLC10A7 gene (611459) on chromosome 4q31.
Description
Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is characterized by disproportionate short stature, defective tooth enamel formation, and skeletal dysplasia with severe scoliosis in some patients. Variable features include facial dysmorphism, moderate hearing impairment, and mildly impaired intellectual development (Ashikov et al., 2018).
Clinical Features
Ashikov et al. (2018) reported a sister and brother and 3 unrelated male patients who exhibited short stature, skeletal dysplasia, amelogenesis imperfecta, and dysmorphic facial features, as well as hearing loss and mild intellectual impairment. Facial dysmorphism included mandibular hypoplasia in 2 patients, prognathism in 1, and cleft palate in 1. Chest deformity was present in 4 patients, scoliosis in 3, and joint hypermobility in 2.
Dubail et al. (2018) studied 6 unrelated patients, 3 originating from Turkey, 2 from the Netherlands, and 1 from Iran, who presented with pre- and postnatal short stature, dislocation of large joints, advanced carpal ossification, 'monkey wrench' appearance of the proximal femora in the first months of life, abnormal vertebrae, luxation of knees with genua valga, hyperlordosis or kyphoscoliosis, and small epiphyses. In addition, all 6 patients exhibited hypomineralized amelogenesis imperfecta, characterized by yellow-brown enamel with a rough surface, and short and widely spaced tooth crowns. Dysmorphic facial features were present in all, including Pierre-Robin sequence (micrognathia, cleft palate and glossoptosis) in 2 patients, micrognathia in 3, and flat face in the remaining patient. Additional features included a heart defect (1 patient), mixed and sensorineural hearing loss (1 patient each), and obesity in the eldest patients. The parents of the Iranian patient had a history of multiple pregnancies that resulted in spontaneous abortion and neonatal death due to respiratory distress accompanied by micromelia; 2 other pregnancies were terminated preterm after the detection of short limbs during ultrasound screening, and 1 of those fetuses had cleft palate.
Molecular Genetics
From a cohort of 19 patients diagnosed with congenital disorders of glycosylation (CDGs; see 212065), who were negative for mutation in known CDG-associated genes, Ashikov et al. (2018) identified compound heterozygosity and homozygosity for mutations in the SLC10A7 gene (see, e.g., 611459.0001-611459.0002) in a brother and sister and an unrelated male infant, respectively, who exhibited skeletal dysplasia and amelogenesis imperfecta. In 2 unrelated similarly affected male patients from the cohort, the authors found complete lack of SLC10A7 cDNA but no mutations, deletions, or insertions involving the SLC10A7 gene were detected in either patient. Patients demonstrated a characteristic glycan pattern, showing an increase in biantennary glycans lacking 1 GlcNAc residue, 4--3-0--1 and 4--3-1--1, and the authors stated that addition of the monosialylated N-glycan 5--4-0--1 and the high mannose glycan 9--2-0--0 achieved complete discrimination of SLC10A7-associated glycosylation disorder.
In 6 patients with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta, Dubail et al. (2018) identified homozygosity for 5 different mutations in the SLC10A7 gene (see, e.g., 611459.0003-611459.0005) that segregated with disease and were not found in 200 control chromosomes or public variant databases.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature, prenatal and postnatal (< -3 SD) \- Disproportionate short stature Weight \- Obesity (in some patients) \- Truncal obesity (in some patients) HEAD & NECK Face \- Round face \- Micrognathia \- Microretrognathia \- Mandibular hypoplasia Ears \- Hearing impairment (in some patients) Mouth \- Pierre-Robin sequence (in some patients) \- Cleft palate \- High palate Teeth \- Amelogenesis imperfecta, hypomineralized \- Discolored enamel \- Rough enamel \- Short crowns \- Widely spaced crowns \- Tooth agenesis (in some patients) \- Dental caries (in some patients) RESPIRATORY \- Respiratory distress at birth CHEST External Features \- Chest deformity (in some patients) \- Small thorax \- Short thorax ABDOMEN Gastrointestinal \- Inguinal hernia (in some patients) SKELETAL \- Decreased bone mass \- Advanced bone age \- Hypermobile joints Spine \- Vertebral anomalies \- Irregular endplates \- Coronal clefts \- Scoliosis \- Hyperlordosis \- Kyphoscoliosis Pelvis \- Abnormally shaped pelvis \- Coxa valga \- Hip contracture Limbs \- Short extremities \- Short tubular bones \- Short femoral necks \- Small epiphyses \- Flat epiphyses \- 'Monkey wrench' appearance of proximal femora in first months of life \- Knee dislocation \- Genua valga Hands \- Advanced carpal ossification Feet \- Pes planus (in some patients) NEUROLOGIC Central Nervous System \- Impaired intellectual development (in some patients) \- Developmental delay (rare) LABORATORY ABNORMALITIES \- N-glycosylation defect \- Reduced sialylation \- Increase of high-mannose glycans MISCELLANEOUS \- Variable dysmorphic features are present MOLECULAR BASIS \- Caused by mutation in the solute carrier family 10 (sodium/bile acid cotransporter family), member 7 gene (SLC10A7, 611459.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| SHORT STATURE, AMELOGENESIS IMPERFECTA, AND SKELETAL DYSPLASIA WITH SCOLIOSIS | None | 3,625 | omim | https://www.omim.org/entry/618363 | 2019-09-22T15:42:22 | {"omim": ["618363"]} |
Dentinogenesis imperfecta
Oral photographs from an individual with Dentinogenesis imperfecta
SpecialtyDentistry
Dentinogenesis imperfecta (DI) is a genetic disorder of tooth development. This condition is a type of dentin dysplasia that causes teeth to be discolored (most often a blue-gray or yellow-brown color) and translucent giving teeth an opalescent sheen.[1] Although genetic factors are the main contributor for the disease, any environmental or systemic upset that impedes calcification or metabolisation of calcium can also result in anomalous dentine.
Consequently, teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss. These problems can affect both primary (deciduous) teeth and permanent teeth. This condition is inherited in an autosomal dominant pattern, as a result of mutations on chromosome 4q21, in the dentine sialophosphoprotein gene (DSPP).[2] It is one of the most frequently occurring autosomal dominant features in humans.[3] Dentinogenesis imperfecta affects an estimated 1 in 6,000 to 8,000 people.
## Contents
* 1 Presentation
* 2 Histology
* 3 Diagnosis
* 3.1 Radiographic features
* 3.2 Types
* 4 Treatment
* 4.1 Management of DI associated with OI
* 5 See also
* 6 References
* 7 External links
## Presentation[edit]
Clinical appearance is variable with presentation ranging from gray to yellowish brown, but the characteristic feature is the translucent or opalescent hue to the teeth.[citation needed]
In Type I, primary teeth are more severely affected compared to the permanent dentition which has more varied features, commonly involving lower incisors and canines. Primary teeth have a more obvious appearance as they have a thinner layer of enamel overlying dentine, hence the color of dentine is more noticeable.
In Type II, both the dentitions are equally affected.
Enamel is usually lost early because it is further inclined to attrition due to loss of scalloping at the dentinoenamel junction (DEJ). It was suggested that the scalloping is beneficial for the mechanical properties of teeth as it reinforces the anchor between enamel and dentine.[4] However, the teeth are not more susceptible to dental caries than normal ones.
However, certain patients with dentinogenesis imperfecta will suffer from multiple periapical abscesses apparently resulting from pulpal strangulation secondary to pulpal obliteration or from pulp exposure due to extensive coronal wear. They may need apical surgery to save the involved teeth.[5]
These features are also present in dentine dysplasia and hence, the condition may initially be misdiagnosed.
## Histology[edit]
Dentinal tubules are irregular and are bigger in diameter. Areas of uncalcified matrix are seen. Sometimes odontoblasts are seen in dentin.
## Diagnosis[edit]
### Radiographic features[edit]
Type I and II have similar radiographic features[6]
* Total obliteration of the pulp chamber and root canals due to deposition of dentine
* Bulbous crowns with apparent cervical constriction
* Reduced root-length with rounded apices
Type III shows thin dentin and extremely enormous pulp chamber. These teeth are usually known as "shell teeth".
Periapical radiolucency may be seen on radiographs but may occur without any apparent clinical pathology.[7]
### Types[edit]
Type I: DI associated with Osteogenesis Imperfecta (OI). Type of DI with similar dental abnormalities usually an autosomal dominant trait with variable expressivity but can be recessive if the associated osteogenesis imperfecta is of recessive type.[8]
Type II: DI not associated with OI. Occurs in people without other inherited disorders (i.e. Osteogenesis imperfecta). It is an autosomal dominant trait. A few families with type II have progressive hearing loss in addition to dental abnormalities. Also called hereditary opalescent dentin.[5]
Type III: Brandywine isolate. This type is rare with occurrences only in the secluded populations in Maryland, USA.[9][7] Its predominant characteristic is bell-shaped crowns, especially in the permanent dentition. Unlike Types I and II, it involves teeth with shell-like appearance and multiple pulp exposures.[5]
Mutations in the DSPP gene have been identified in people with type II and type III dentinogenesis imperfecta. Type I occurs as part of osteogenesis imperfecta.
## Treatment[edit]
Preventive and restorative care are important as well as esthetics as a consideration. This ensures preservation of the patient's vertical face height between their upper and lower teeth when they bite together. The basis of treatment is standard throughout the different types of DI where prevention, preservation of occlusal face height, maintenance of function, and aesthetic needs are priority. Preventive efforts can limit pathology occurring within the pulp, which may render future endodontic procedures less challenging, with better outcomes.
* Challenges are associated with root canal treatment of teeth affected by DI due to pulp chamber and root canal obliteration, or narrowing of such spaces.
* If root canal treatment is indicated, it should be done in a similar way like with any other tooth.[10] Further consideration is given for restoring the root-treated tooth as it has weaker dentine which may not withstand the restoration.
Preservation of occlusal face height may be tackled by use of stainless steel crowns which are advocated for primary teeth where occlusal face height may be hugely compromised due to loss of tooth tissue as a result of attrition, erosion of enamel.[7]
In most cases, full-coverage crowns or veneers (composite/porcelain) are needed for aesthetic appearance, as well as to prevent further attrition.[1] Another treatment option is bonding, putting lighter enamel on the weakened enamel of the teeth and with many treatments of this bonding, the teeth appear whiter to the eye, but the teeth on the inside and under that cover are still the same. Due to the weakened condition of the teeth, many common cosmetic procedures such as braces and bridges are inappropriate for patients with Dentinogenesis imperfecta and are likely to cause even more damage than the situation they were intended to correct.
Dental whitening (bleaching) is contraindicated although it has been reported to lighten the color of DI teeth with some success; however, because the discoloration is caused primarily by the underlying yellow-brown dentin, this alone is unlikely to produce normal appearance in cases of significant discoloration.[5]
If there is considerable attrition, overdentures may be prescribed to prevent further attrition of remaining teeth and for preserving the occlusal face height.[7]
### Management of DI associated with OI[edit]
Bisphosphonates have recently been introduced to treat several bone disorders, which include osteogenesis imperfecta.
A recognized risk of this drug relevant to dental treatments is bisphosphonate-associated osteonecrosis of the jaw (BRONJ).[11][12] Occurrences of this risk is associated with dental surgical procedures such as extractions.
Dental professionals should therefore proceed with caution when carrying out any dental procedures in patients who have Type 2 DI who may be on bisphosphonate drug therapy.
## See also[edit]
* Dentin
* Dentinogenesis
* Tooth development
* Osteogenesis imperfecta
## References[edit]
1. ^ a b Illustrated Dental Embryology, Histology, and Anatomy, Bath-Balogh and Fehrenbach, Elsevier, 2011, page 64
2. ^ Beattie ML, Kim JW, Gong SG, Murdoch-Kinch CA, Simmer JP, Hu JC (2006). "Phenotypic variation in dentinogenesis imperfecta/dentin dysplasia linked to 4q21". J Dent Res. 85 (4): 329–333. doi:10.1177/154405910608500409. PMC 2238637. PMID 16567553.
3. ^ Thotakura SR, Mah T, Srinivasan R, Takagi Y, Veis A, George A (2000). "The noncollagenous dentin matrix proteins are involved in dentinogenesis imperfecta type II (DGI-II)". J Dent Res. 79 (3): 835–839. doi:10.1177/00220345000790030901. PMID 10765957. S2CID 38418321.
4. ^ Shimizu D, Macho GA (2007). "Functional significance of the microstructural detail of the primate dentino-enamel junction: a possible example of exaptation". Journal of Human Evolution. Jan, 52(1) (1): 103–111. doi:10.1016/j.jhevol.2006.08.004. PMID 16997355.
5. ^ a b c d American Academy of Pediatric Dentistry, Guideline on Dental Management of Heritable Dental Developmental Anomalies, 2013, http://www.aapd.org/media/Policies_Guidelines/G_OHCHeritable.pdf
6. ^ Rios D, Falavinha A, Tenuta L, Machado M (2005). Osteogenesis imperfecta and dentinogenesis imperfecta: associated disorders. Quintessence Int. pp. 695–701. PMID 16163872.
7. ^ a b c d Pettiette M, Wright JT, Trope M (1998). "Dentinogenesis imperfecta: endodontic implications. Case report". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 86 (6): 733–737. doi:10.1016/s1079-2104(98)90213-x. PMID 9868734.
8. ^ Ten Cate's Oral Histology, Nanci, Elsevier, 2013, page 15
9. ^ Huth KC, Paschos E, Sagner T, Hickel R (2002). "Diagnostic features and pedodontic-orthodontic management in dentinogenesis imperfecta type II: a case report". Int J Paed Dent. 1 2 (5): 316–321. doi:10.1046/j.1365-263X.2002.00390.x. PMID 12199890.
10. ^ Henke DA, Todd AF, Aquilino SA (1999). "Occlusal rehabilitation of a patient with dentinogenesis imperfecta: a clinical report". J Prosthet Dent. 81 (5): 503–506. doi:10.1016/s0022-3913(99)70201-5. PMID 10220651.
11. ^ Woo SB, Hellstein JW, Kalmar JR (2006). "Systematic review: bisphosphonates and osteonecrosis of the jaws". Ann Intern Med. 144 (10): 753–761. doi:10.7326/0003-4819-144-10-200605160-00009. PMID 16702591. S2CID 53091343.
12. ^ Khosla; et al. (2007). "Bisphosphonate associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research". J Bone Miner Res. 22 (10): 1479–1491. doi:10.1359/jbmr.0707onj. PMID 17663640.
This article incorporates public domain text from The U.S. National Library of Medicine
## External links[edit]
Classification
D
* ICD-10: K00.5
* ICD-9-CM: 520.5
* MeSH: D003811
* SNOMED CT: 196286005
External resources
* Orphanet: 49042
* v
* t
* e
Developmental tooth disease/tooth abnormality
Quantity
* Anodontia/Hypodontia
* Hyperdontia
Shape and size
* Concrescence
* Fusion
* Gemination
* Dens evaginatus/Talon cusp
* Dens invaginatus
* Enamel pearl
* Macrodontia
* Microdontia
* Taurodontism
* Supernumerary roots
Formation
* Dilaceration
* Regional odontodysplasia
* Turner's hypoplasia
* Enamel hypoplasia
* Ectopic enamel
Other hereditary
* Amelogenesis imperfecta
* Dentinogenesis imperfecta
* Dentin dysplasia
* Regional odontodysplasia
Other
* Dental fluorosis
* Tooth impaction
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Dentinogenesis imperfecta | c0011436 | 3,626 | wikipedia | https://en.wikipedia.org/wiki/Dentinogenesis_imperfecta | 2021-01-18T18:49:33 | {"gard": ["6258"], "mesh": ["D003811"], "umls": ["C0011436"], "icd-9": ["520.5"], "orphanet": ["167762", "49042"], "wikidata": ["Q548984"]} |
A number sign (#) is used with this entry because of evidence that spinal muscular atrophy with congenital bone fractures-1 (SMABF1) is caused by homozygous or compound heterozygous mutation in the TRIP4 gene (604501) on chromosome 15q22.
Description
Spinal muscular atrophy with congenital bone fractures is an autosomal recessive severe neuromuscular disorder characterized by onset of severe hypotonia in utero. This results in congenital contractures, consistent with arthrogryposis multiplex congenita, and increased incidence of prenatal fracture of the long bones. Affected infants have difficulty breathing and feeding and often die in the first months or years of life (summary by Knierim et al., 2016).
### Genetic Heterogeneity of Spinal Muscular Atrophy With Congenital Bone Fractures
See also SMABF2 (616867), caused by mutation in the ASCC1 gene (614215) on chromosome 10q22.
Clinical Features
Knierim et al. (2016) reported 5 patients from 3 unrelated families who were born with distal and proximal joint contractures and generalized severe muscle atrophy. Two of the families were of Kosovan descent and 1 was of Albanian descent. Three of 4 patients evaluated had fractures of the long bones. A sixth patient in 1 of the families, a fetus, was also affected. Reduced fetal movements were apparent during pregnancy, and 3 pregnancies were complicated by oligohydramnios. Deep tendon reflexes were absent, muscles did not contract upon electrical stimulation, and neurography was consistent with axonal neuropathy. The patients needed ventilatory assistance and fed poorly. Additional variable features included microretrognathia, hypertelorism, high palate, and narrow mouth, as well as cardiac malformations, including patent foramen ovale, atrial septal defects, and patent ductus arteriosus. Skeletal muscle biopsy showed muscle fiber immaturity, fiber size variation, and atrophic fibers, suggestive of spinal muscular atrophy. Spinal cord analysis in 1 patient showed apoptotic alpha-motoneurons. Sural nerve biopsy of 2 patients showed signs of unmyelinated axon loss. Most children died from respiratory failure between 2 weeks and 16 months of age; 1 died of cardiac failure.
Inheritance
The transmission pattern of SMABF1 in the families reported by Knierim et al. (2016) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 5 patients from 3 unrelated families with spinal muscular atrophy with SMABF1, Knierim et al. (2016) identified homozygous or compound heterozygous truncating mutations in the TRIP4 gene (604501.0001 and 604501.0002). The mutations in the first 2 families were found by a combination of autozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing; mutations in the fifth patient from the third family were found by sequencing the TRIP4 gene in 11 unrelated children with a similar disorder. Messenger RNA carrying either mutation was able to rescue the motor defects in morpholino-knockout zebrafish embryos.
Animal Model
Knierim et al. (2016) found that morpholino knockdown of the trip4 gene in zebrafish embryos resulted in a severe impairment of axonal outgrowth of alpha-motoneurons, as well as impaired formation of the neuromuscular junction and organization of the myotome. Mutant zebrafish showed compromised motor responses.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Microretrognathia Eyes \- Hypertelorism Mouth \- Narrow mouth \- High-arched palate CARDIOVASCULAR Heart \- Patent foramen ovale \- Atrial septal defect \- Cardiac failure (in some patients) Vascular \- Patent ductus arteriosus RESPIRATORY \- Respiratory distress due to hypotonia Lung \- Pulmonary hypoplasia ABDOMEN Gastrointestinal \- Poor feeding due to hypotonia SKELETAL \- Arthrogryposis, distal and proximal Limbs \- Fractures, congenital, of the long bones MUSCLE, SOFT TISSUES \- Hypotonia, generalized, severe \- Muscles do not contract upon electrical stimulation \- Muscle fiber immaturity \- Muscle fiber size variation \- Neurogenic atrophy NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Spinal muscular atrophy \- Alpha-motor neuron degeneration in the spinal cord Peripheral Nervous System \- Axonal neuropathy \- Unmyelinated axonal loss \- Areflexia PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements Amniotic Fluid \- Oligohydramnios MISCELLANEOUS \- Onset in utero \- Most patients die in the first months or years of life MOLECULAR BASIS \- Caused by mutation in the thyroid hormone receptor interactor 4 gene (TRIP4, 604501.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| SPINAL MUSCULAR ATROPHY WITH CONGENITAL BONE FRACTURES 1 | c4225177 | 3,627 | omim | https://www.omim.org/entry/616866 | 2019-09-22T15:47:40 | {"omim": ["616866"], "orphanet": ["486811"], "synonyms": ["SMABF"]} |
A number sign (#) is used with this entry because of evidence that congenital stromal corneal dystrophy (CSCD) is caused by heterozygous mutation in the gene encoding decorin (DCN; 125255) on chromosome 12q21.
Description
Congenital stromal corneal dystrophy (CSCD) is a rare autosomal dominant eye disease characterized by diffuse bilateral corneal clouding with flake-like whitish opacities throughout the stroma. These small flakes and spots are present at or shortly after birth and are thought to become more numerous with age. Some affected individuals may have strabismus or nystagmus. Normal corneal thickness, horizontal diameter, and endothelial function distinguish the condition from congenital corneal opacifications such as congenital hereditary endothelial dystrophy (see 121700), posterior polymorphous dystrophy (see 122000), and congenital glaucoma (see 137760). Most individuals undergo a penetrating keratoplasty in late adolescence or in early adulthood with good results (summary by Kim et al., 2011 and Jing et al., 2014).
Clinical Features
Odland (1968) described a Norwegian family with autosomal dominant inheritance of congenital corneal opacities that consisted of a large number of flakes and spots throughout all layers of the stroma. In 4 generations there were 11 affected members. Opacities increased with age.
Bredrup et al. (2005) restudied the family of Odland (1968) into the fifth generation. The opacities, which were equally pronounced in all areas of the cornea, prohibited detailed clinical study of the endothelium. Fluorescein staining revealed no signs of vascularization. Corneal sensitivity was normal or slightly reduced. The patients did not have other ocular symptoms, especially corneal erosions or photophobia. Four of 11 affected family members had strabismus (3 esotropia, 1 exotropia). Three eyes from 2 individuals had primary open-angle glaucoma No systemic abnormalities or malformations were recorded. Specifically, there were no recognized problems related to skin, teeth, joints, or bones.
Turpin et al. (1939) and Desvignes and Vigo (1955) studied the same French family in which 13 were affected in 3 consecutive generations with 5 instances of male-to-male transmission. Witschel et al. (1978) reported a branch of this family and another unrelated pedigree. Pouliquen et al. (1979) included the family of Turpin et al. (1939) in their report. Van Ginderdeuren et al. (2002) reported an affected mother and son. Bredrup et al. (2005) summarized the clinical findings in these and their own studies.
Kim et al. (2011) described a 29-year-old Korean woman and her 1-year-old daughter who both had bilateral diffuse corneal opacity from birth, with only slightly increased central corneal thickness and no photophobia, nystagmus, or strabismus. Electron microscopy of surgically excised stroma showed features similar to those of previous reports, with normal lamellae composed of collagen but separated by abnormal fibers randomly arranged in electron-lucent layers. The appearance of the corneal epithelium and the basement membrane was within normal limits, and normal keratocytes without inclusions were also seen.
Jing et al. (2014) studied a 3-generation Chinese family in which 5 members had CSCD. Confocal microscopy and optical coherence tomography (OCT) analysis demonstrated that corneal opacities develop throughout the stromal layers, with more opacities in the anterior stroma and scattered opacities in the posterior peripheral stroma. Electron microscopic findings were similar to those of Witschel et al. (1978), with abundant irregularly arranged, slightly thinned collagen filaments between normal-appearing collagen lamellae. In electron-lucent zones, the poorly formed collagen filaments were much thinner, with a diameter about half that of normal fibrils.
Clinical Management
Odland (1968) reported that 2 of the affected individuals had undergone keratoplasty, one lamellar and the other penetrating. Both types of grafts improved the visual acuity significantly, restoring reading vision, and were clear at the time of publication.
At the time of the report of Bredrup et al. (2005), 18 eyes had been treated with penetrating keratoplasty, with 7 individuals having been treated bilaterally and the remaining 4 unilaterally. The mean age at surgery was 20 years (range, 6-44 years). Ten of 18 transplanted corneas were clear, whereas 6 showed minimal changes; 2 patients had 1 eye with moderate to severe opacities, similar to those of the remaining host cornea. Both Odland (1968) and Bredrup et al. (2005) described the histopathology of the buttons removed during keratoplasty, noting diffuse stromal edema and disorganization of the fibrillar architecture of the corneal lamellae.
Inheritance
The transmission pattern of congenital stromal corneal dystrophy in the families reported by Odland (1968) and Turpin et al. (1939) was consistent with autosomal dominant inheritance.
Mapping
Bredrup et al. (2005) performed a genomewide screening that revealed linkage to chromosome 12q22 with a maximum lod score of 4.68 at marker D12S351. High-resolution mapping subsequently narrowed the candidate region to an 8.4-Mb region between markers D12S1719 and D12S101.
Molecular Genetics
Bredrup et al. (2005) identified a heterozygous deletion of 1 bp in exon 10 of the decorin gene (125255.0001) in all affected members of the family originally described by Odland (1968). Bredrup et al. (2005) postulated that the defective interaction of mutant decorin with collagen would disturb the regularity of corneal collagen in affected heterozygotes.
In the Belgian mother and son with CSCD originally reported by van Ginderdeuren et al. (2002), Rodahl et al. (2006) identified heterozygosity for a 1-bp deletion in the DCN gene (125255.0002), causing a frameshift predicted to result in a stop codon at the same codon as the frameshift mutation (125255.0001) in the Norwegian family studied by Bredrup et al. (2005). In contrast to affected individuals in the Norwegian family, the Belgian mother and son both had severe photophobia, and the affected corneas appeared to be of normal thickness.
In a Korean mother and daughter with CSCD, Kim et al. (2011) identified heterozygosity for a 1-bp deletion in DCN (125255.0003); the mutation was not found in the mother's unaffected son.
In 5 affected members of a 3-generation Chinese family segregating autosomal dominant CSCD, Jing et al. (2014) identified heterozygosity for a 1-bp deletion in the DCN gene (125255.0004) that was not present in unaffected family members or in 50 healthy controls. Jing et al. (2014) noted that all 4 CSCD-associated frameshift mutations that had been reported cause a premature termination codon with loss of the 33 C-terminal amino acids of the decorin proteoglycan, suggesting that exon 8 is a mutational hotspot and a functionally important region of DCN.
Animal Model
Mellgren et al. (2015) found that mice with a knock-in Dcn 952delT mutation, corresponding to the human 927delT mutation in CSCD, did not show any histologic organ pathology. Their corneas were clear, and the electron-lucent deposits observed in CSCD were not present. Whereas nearly equivalent amounts of normal and truncated decorin were present in CSCD corneas, truncated decorin was hardly detectable in the mouse corneas. By immunofluorescence analysis of the corneas from 952delT homozygous mice, decorin was found only in keratocytes. Truncated decorin was retained intracellularly in cells from mouse corneal explants, whereas truncated decorin was exported into the culture medium in cells from human CSCD corneas. Immunofluorescence analysis revealed that native mouse decorin localized within the Golgi complex, whereas the truncated decorin accumulated in the endoplasmic reticulum. Mellgren et al. (2015) concluded that export of truncated decorin appeared to be a prerequisite to produce the amorphous deposits of decorin typical of CSCD and that the Dcn 952delT knock-in mice are not a suitable model for CSCD.
INHERITANCE \- Autosomal dominant HEAD & NECK Eyes \- Corneal stromal opacification, congenital progressive \- Visual loss, progressive painless \- Increased corneal thickness \- Abnormal fibrils in stroma on electron microscopy \- No corneal erosions \- Photophobia, severe (rare) MISCELLANEOUS \- Complete penetrance MOLECULAR BASIS \- Caused by mutation in the decorin gene (DCN, 125255.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| CORNEAL DYSTROPHY, CONGENITAL STROMAL | c1864738 | 3,628 | omim | https://www.omim.org/entry/610048 | 2019-09-22T16:05:13 | {"doid": ["0060445"], "mesh": ["C566452"], "omim": ["610048"], "orphanet": ["101068"], "synonyms": ["Alternative titles", "CONGENITAL STROMAL CORNEAL DYSTROPHY"], "genereviews": ["NBK2690"]} |
A number sign (#) is used with this entry because of evidence that lymphatic malformation-6 (LMPHM6) is caused by homozygous or compound heterozygous mutation in the PIEZO1 gene (611184) on chromosome 16q24.
Description
Lymphatic malformation-6 is a form of generalized lymphatic dysplasia (GLD), which is characterized by a uniform, widespread lymphedema affecting all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions. In LMPHM6, there is a high incidence of nonimmune hydrops fetalis (NIHF) with either death or complete resolution of the neonatal edema, but childhood onset of lymphedema with or without systemic involvement also occurs. Mild facial edema is often present. Patients have normal intelligence and no seizures (summary by Fotiou et al., 2015).
For a discussion of genetic heterogeneity of lymphatic malformation, see 153100.
Clinical Features
Fotiou et al. (2015) identified 2 sib pairs and 1 sporadic case of GLD with mutations in the PIEZO1 gene. Nonimmune hydrops fetalis was documented in 2 of the families, with in utero death of 1 sib. Postnatally, the edema associated with the hydrops resolved completely in the other patients, but they re-presented with lymphedema of the peripheries in early childhood. Two of them suffered from intermittent, severe facial swelling due to recurrent cellulitis, which is rarely seen in other forms of primary lymphedema. There was no history of hemolytic anemia, and the immune profiles for both sibs were normal. None of the patients had dysmorphic features, learning disabilities, or seizures and the swelling was not severe. Fotiou et al. (2015) identified 5 additional patients from 3 similarly affected families with a PIEZO1 mutation. Of the 10 patients, 7 had NIHF and 2 died in utero; survivors re-presented with lymphedema of the peripheries (mainly lower limbs but also arms, 4 patients), face (3 patients), or genitalia (1 patient), with or without chylothoraces (2 patients) or intestinal lymphangiectasia (1 patient). Fotiou et al. (2015) inspected blood films of the patients and identified subtle changes consistent with a mild and asymptomatic form of dehydrated hereditary stomatocytosis (see DHS1, 194380). Two affected sibs showed marked spherocytosis, whereas the blood film from their carrier mother was unremarkable with only occasional spherocytes. Four patients had severe, recurrent facial cellulitis with significant morbidity (high pyrexia and frequent admission to intensive care).
Inheritance
Lymphatic malformation-6 is an autosomal recessive disorder (Fotiou et al., 2015).
Mucke et al. (1986) observed 2 brothers with chronic congenital lymphedema and proposed the existence of an X-linked or recessive form. In addition to edema of the limbs, they had abnormalities of the external genitalia as a deformation sequence resulting from intrauterine edema and had intestinal lymphedema. A prominent feature also was chemosis and injection of the conjunctiva.
Molecular Genetics
In 10 patients from 6 families with generalized lymphatic dysplasia who did not have mutations in the CCBE1 (612753) or FAT4 (612411) genes, Fotiou et al. (2015) identified homozygous or compound heterozygous mutations in the PIEZO1 gene (see, e.g., 611184.0009-611184.0015). The first mutations were identified by whole-exome sequencing and later mutations were identified by exome sequencing of all PIEZO1 exons and their associated splice sites. The mutations segregated with the phenotype in the families. None of the variants, except for 2 found in cis, were found in the dbSNP or 1000 Genomes Project databases or in 900 control samples.
INHERITANCE \- Autosomal recessive GROWTH Height \- Short stature HEAD & NECK Face \- Facial swelling \- Recurrent facial cellulitis \- Micrognathia Ears \- Cupped ears \- Simple ears \- Deafness, bilateral sensorineural (uncommon) Eyes \- Periorbital edema \- Epicanthic folds Neck \- Swelling of the neck \- Webbed neck CARDIOVASCULAR Heart \- Atrial septal defect Vascular \- Deep vein thrombosis \- Varicose veins \- Generalized edema RESPIRATORY \- Chylothorax \- Pleural effusions, bilateral CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum Diaphragm \- Amyoplasia of diaphragm ABDOMEN External Features \- Ascites \- Prune belly Spleen \- Splenomegaly Gastrointestinal \- Gastroesophageal reflux \- Intestinal lymphangiectasia GENITOURINARY External Genitalia (Male) \- Hydrocele \- Genital edema External Genitalia (Female) \- Genital edema SKELETAL Spine \- Scoliosis SKIN, NAILS, & HAIR Skin \- Granuloma annulare MUSCLE, SOFT TISSUES \- Lymphedema (primarily in lower limbs, but also arms in some patients) \- Cellulitis in lower limbs, recurrent \- Deep rerouting of lymph in lower limbs seen on lymphoscintigraphy \- Superficial rerouting of lymph through the skin NEUROLOGIC Central Nervous System \- Developmental delay, mild ENDOCRINE FEATURES \- Hypothyroidism IMMUNOLOGY \- Normal immune profile PRENATAL MANIFESTATIONS \- Nonimmune hydrops fetalis Amniotic Fluid \- Polyhydramnios MISCELLANEOUS \- Variable phenotype MOLECULAR BASIS \- Caused by mutation in the PIEZO1 ion channel gene (PIEZO1, 611184.0009 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| LYMPHATIC MALFORMATION 6 | c4225184 | 3,629 | omim | https://www.omim.org/entry/616843 | 2019-09-22T15:47:45 | {"omim": ["616843"], "synonyms": ["Alternative titles", "GENERALIZED LYMPHATIC DYSPLASIA OF FOTIOU", "LYMPHEDEMA, HEREDITARY, III, FORMERLY"]} |
Overflow incontinence
Other namesischuria paradoxa
CT scan in the sagittal plane which reveals a greatly enlarged urinary bladder caused by urinary retention, a condition which often leads to overflow incontinence.
SpecialtyUrology
Overflow incontinence is a form of urinary incontinence, characterized by the involuntary release of urine from an overfull urinary bladder, often in the absence of any urge to urinate. This condition occurs in people who have a blockage of the bladder outlet (benign prostatic hyperplasia, prostate cancer, or narrowing of the urethra), or when the muscle that expels urine from the bladder is too weak to empty the bladder normally. Overflow incontinence may also be a side effect of certain medications.
## Contents
* 1 Causes
* 2 Pathophysiology
* 3 Diagnosis
* 4 Management
* 5 See also
* 6 References
* 7 External links
## Causes[edit]
Lesions affecting sacral segments or peripheral autonomic fibres result in atonic bladder with loss of sphincteric coordination. This results in loss of detrusor contraction, difficulty in initiating micturition and overflow incontinence. Anticholinergic side effects of certain medications (for example, certain antipsychotics and antidepressants) may cause urinary retention which may lead to overflow incontinence. Alpha-adrenergic agonists may cause urinary retention by stimulating the contraction of the urethral sphincter. Calcium channel blockers may decrease the contractility of the smooth muscle tissue in the urinary bladder, causing urinary retention with overflow incontinence.[1] Epidural anesthesia and delivery also can cause the overflow incontinence.
## Pathophysiology[edit]
Overflow incontinence occurs when the patient's bladder is always full so that it frequently leaks urine. Weak bladder muscles, resulting in incomplete emptying of the bladder, or a blocked urethra can cause this type of incontinence. Autonomic neuropathy from diabetes or other diseases (e.g. Multiple sclerosis) can decrease neural signals from the bladder (allowing for overfilling) and may also decrease the expulsion of urine by the detrusor muscle (allowing for urinary retention). Additionally, tumors and kidney stones can block the urethra. Spinal cord injuries or nervous system disorders are additional causes of overflow incontinence. In men, benign prostatic hyperplasia (BPH) may also restrict the flow of urine. Overflow incontinence is rare in women, although sometimes it is caused by fibroid or ovarian tumors. Also overflow incontinence can be from increased outlet resistance from advanced vaginal prolapse causing a "kink" in the urethra or after an anti-incontinence procedure which has overcorrected the problem.[2] Early symptoms include a hesitant or slow stream of urine during voluntary urination. Anticholinergic and NSAIDs medications may worsen overflow incontinence.
## Diagnosis[edit]
The gold standard for all urinary incontinence is an urodynamic study that looks for bladder capacity, detrusor stability, contractility, and voiding ability (cystometry).
## Management[edit]
Medications
Bethanechol (Management of overflow incontinence by activating muscarinic receptors in the bladder and stimulating contraction to void the urine, NOT a treatment modality; must rule out urinary obstruction prior to use.)
Surgery
Catheterization
If an incontinence is due to overflow incontinence, in which the bladder never empties completely, or if the bladder cannot empty because of poor muscle tone, past surgery, or spinal cord injury, a catheter may be used to empty the bladder. A catheter is a tube that can be inserted through the urethra into the bladder to drain urine. Catheters may be used once in a while or on a constant basis, in which case the tube connects to a bag that is attached to the leg. If a long-term (or indwelling) catheter is used, urinary tract infections may occur.
## See also[edit]
* Bladder sphincter dyssynergia
* Overactive bladder
## References[edit]
1. ^ Vasavada SP, Carmel ME, Rackley R (2012). "Urinary incontinence". Medscape. New York: WebMD. Retrieved 2012-07-28.
2. ^ Christopher M. Tarnay, MD & Narender N. Bhatia, MD (2006). "Overflow Incontinence". Urinary Incontinence - Overview. Armenian Medical Network. Retrieved 2006-12-20.
## External links[edit]
Classification
D
* ICD-10: N39.4
* ICD-9-CM: 788.38
* v
* t
* e
Diseases of the urinary tract
Ureter
* Ureteritis
* Ureterocele
* Megaureter
Bladder
* Cystitis
* Interstitial cystitis
* Hunner's ulcer
* Trigonitis
* Hemorrhagic cystitis
* Neurogenic bladder dysfunction
* Bladder sphincter dyssynergia
* Vesicointestinal fistula
* Vesicoureteral reflux
Urethra
* Urethritis
* Non-gonococcal urethritis
* Urethral syndrome
* Urethral stricture
* Meatal stenosis
* Urethral caruncle
Any/all
* Obstructive uropathy
* Urinary tract infection
* Retroperitoneal fibrosis
* Urolithiasis
* Bladder stone
* Kidney stone
* Renal colic
* Malakoplakia
* Urinary incontinence
* Stress
* Urge
* Overflow
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Overflow incontinence | c0312413 | 3,630 | wikipedia | https://en.wikipedia.org/wiki/Overflow_incontinence | 2021-01-18T18:49:57 | {"icd-9": ["788.38"], "icd-10": ["N39.4"], "wikidata": ["Q7113655"]} |
Dentinogenesis imperfecta type 3 is a rare and severe form of dentinogenesis imperfecta, a condition that affects tooth development. People affected by this condition generally have discolored (most often a blue-gray or yellow-brown color) and translucent teeth. Teeth are also weaker than normal, making them prone to rapid wear, breakage, and loss. These problems can affect both primary (baby) teeth and permanent teeth. Dentinogenesis imperfecta type 3 is caused by changes (mutations) in the DSPP gene which are inherited in an autosomal dominant manner. Treatment is usually focused on protecting primary (baby) and then permanent teeth with preformed pediatric crowns and other interventions. The replacement of teeth might be considered in the future with dentures and/or implants.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Dentinogenesis imperfecta type 3 | c0399378 | 3,631 | gard | https://rarediseases.info.nih.gov/diseases/10144/dentinogenesis-imperfecta-type-3 | 2021-01-18T18:00:55 | {"mesh": ["C538216"], "omim": ["125500"], "umls": ["C0399378"], "orphanet": ["166265"], "synonyms": ["Dentinogenesis imperfecta type III", "Brandywine type dentinogenesis imperfecta", "Dentinogenesis imperfecta Shields type 3 ", "Dentinogenesis imperfecta, Shields type 3"]} |
A number sign (#) is used with this entry because this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A7; MDDGA7) is caused by homozygous or compound heterozygous mutation in the ISPD gene (614631) on chromosome 7p21. ISPD encodes an isoprenoid synthase domain-containing protein.
Mutation in the ISPD gene can also cause a less severe limb-girdle muscular dystrophy-dystroglycanopathy without brain and eye anomalies (type C7; MDDGC7; 616052).
Description
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A), which includes both the more severe Walker-Warburg syndrome (WWS) and the slightly less severe muscle-eye-brain disease (MEB), is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, congenital muscular dystrophy, and death usually in the first years of life. It represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (summary by Roscioli et al., 2012).
For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Clinical Features
Chitayat et al. (1995) reported a 37-week-old fetus who was found to have hydrocephalus and retinal detachment on prenatal ultrasound, leading to a diagnosis of WWS. Fetal movements were weak. After delivery, the baby was hypotonic, in a 'frog leg' position, and did not move or cry. He had large fontanels, frontal bossing, deep-set eyes, retrognathia, and small, simple, low-set ears. The eyes had central circular defects in the posterior cornea with abnormal adhesions and anterior segment anomalies consistent with a variant of Peters anomaly. Brain MRI showed hydrocephalus, type II lissencephaly, and cerebellar hypoplasia. He died at age 3 months. Vajsar et al. (2000) performed skeletal muscle studies of the patient reported by Chitayat et al. (1995). Skeletal muscle biopsy showed dystrophic changes and disruption in the basal lamina. Laminin alpha-2 (LAMA2; 156225) immunostaining was normal.
Kanoff et al. (1998) reported a male infant with WWS. He had macrocephaly, low-set ears, unilateral microphthalmia, cataract, and optic nerve hypoplasia. He had a weak cry, facial weakness, and generalized profound hypotonia with absent reflexes. Brain MRI showed ventriculomegaly, a Dandy-Walker malformation, and agyria. Serum creatine kinase was increased, and skeletal muscle biopsy showed necrotic fibers and variation in myofiber diameter, consistent with muscular dystrophy. He died at age 6 months of respiratory impairment. Postmortem examination showed lissencephaly, absence of the posterior cerebellar vermis, atrophy of the corpus callosum, and subcortical heterotopia. There was a decrease in LAMA2 expression in muscle fibers.
Willer et al. (2012) reported 7 patients, including 2 sibs, with MDDGA7 confirmed by genetic analysis. All had a diagnosis of Walker-Warburg syndrome. Two of the patients were those reported by Chitayat et al. (1995) and Kanoff et al. (1998). One additional patient was described in detail by Willer et al. (2012). Brain MRI performed at 3 days and at 5 months of age showed hydrocephalus, cobblestone lissencephaly of the cerebral cortex, and severe brainstem and cerebellar hypoplasia. The patient also had severe muscular dystrophy with increased serum creatine kinase, bilateral microphthalmia, cataracts, and arrested retinal development. Immunofluorescence and protein blot analysis of skeletal muscle showed a typical alpha-dystroglycan glycosylation defect, with loss of both functional glycosylation and receptor function. Fibroblasts from 5 other patients showed a complete loss of functional glycosylation and laminin binding, as well as hypoglycosylation of core alpha-dystroglycan. All patients had a similar phenotype, with muscular dystrophy and brain and eye anomalies. Most died by age 2 years.
Roscioli et al. (2012) reported 9 families with WWS/MEB. One large consanguineous family had 3 affected members. All affected individuals had a severe phenotype, with cobblestone lissencephaly, hydrocephalus, cerebellar hypoplasia, and hypoplasia of the corpus callosum, as well as eye anomalies, such as microphthalmia, cataract, anterior chamber defects, and glaucoma. All had hypotonia and increased serum creatine kinase, and muscle histology showed dystrophic changes and a reduction of glycosylated alpha-dystroglycan. Most died by age 2 years, but 2 patients survived past age 2 and were thus categorized as having MEB.
Vuillaumier-Barrot et al. (2012) reported 8 fetuses from 5 unrelated families with MDDGA7. The probands were ascertained from a larger study of patients with severe diffuse cobblestone lissencephaly. Additional more variable clinical features included neural tube defects (in 4 patients), limb deformations (in 3), visceral malformations (in 2), brain vascular anomalies (in 2), and retinal dysplasia (in all 5 that were examined). One patient had gonadal dysgenesis.
Molecular Genetics
In 7 patients, including a pair of sibs, with congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A7, Willer et al. (2012) identified homozygosity or compound heterozygosity for point mutations in or deletions involving the ISPD gene (see, e.g., 614631.0001-614631.0004). All mutations were predicted to damage or abolish protein function. The mutations were identified by using a cell fusion complementation assay in fibroblasts followed by linkage analysis and targeted exome sequencing within the candidate region on chromosome 7p. Expression of wildtype ISPD in patient-derived cells restored functional glycosylation, confirming that the mutations have pathogenic relevance. Studies of skeletal muscle and fibroblasts from the patients showed a typical alpha-dystroglycan glycosylation defect, with loss of both functional glycosylation and laminin binding.
Roscioli et al. (2012) identified homozygous or compound heterozygous mutations in or deletions involving the ISPD gene in 9 (10%) of 94 families with MDDGA7 (see, e.g., 614631.0005-614631.0008). The gene was initially found by homozygosity mapping of 30 consanguineous families combined with array CGH for copy number variations, as well as exome sequencing of the candidate region in 1 family.
Vuillaumier-Barrot et al. (2012) identified 9 different biallelic mutations or deletions in the ISPD gene (see, e,g., 614631.0009-614631.0013) in 8 fetuses from 5 unrelated families with MDDGA7. The mutations in the first family were found by linkage analysis combined with exome sequencing. ISPD mutations accounted for 5 (9%) of 58 families with cobblestone lissencephaly in whom a genetic defect was found.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly \- Frontal bossing Face \- Retrognathia Ears \- Small ears \- Low-set ears Eyes \- Deep-set eyes \- Microphthalmia \- Cataracts \- Persistent hyperplastic primary vitreous \- Arrested retinal development \- Retinal detachment \- Retinal dysplasia \- Optic nerve hypoplasia \- Peters anomaly \- Glaucoma ABDOMEN \- Visceral malformations (in some patients) SKELETAL Limbs \- Limb deformations (in some patients) Hands \- Adducted thumbs MUSCLE, SOFT TISSUES \- Hypotonia \- Muscular dystrophy \- Disruption in the basal lamina seen on skeletal muscle biopsy \- Defect in glycosylation of alpha-dystroglycan seen on skeletal muscle biopsy NEUROLOGIC Central Nervous System \- Hypotonia \- Mental retardation, profound \- Hydrocephalus \- Ventriculomegaly \- Encephalocele \- Dandy-Walker malformation \- Cobblestone lissencephaly \- Agyria \- Pachygyria \- Polymicrogyria \- Hypoplasia of the corpus callosum \- Partial agenesis of the corpus callosum \- Cortical thinning \- Subcortical heterotopia \- Cerebellar hypoplasia \- Brainstem hypoplasia \- Brain vascular anomalies (rare) Peripheral Nervous System \- Areflexia PRENATAL MANIFESTATIONS Movement \- Decreased fetal movements LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset prenatally or at birth \- Severe phenotype \- Most patients die in first years of life MOLECULAR BASIS \- Caused by mutation in the isoprenoid synthase domain-containing protein gene (ISPD, 614631.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 7 | c0265221 | 3,632 | omim | https://www.omim.org/entry/614643 | 2019-09-22T15:54:38 | {"doid": ["0111234"], "mesh": ["D058494"], "omim": ["614643"], "orphanet": ["899"], "synonyms": ["Alternative titles", "WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, ISPD-RELATED"]} |
Visceral larva migrans
SpecialtyInfectious disease
Visceral larva migrans (VLM) is a condition in humans caused by the migratory larvae of certain nematodes, humans being a dead-end host, and was first reported in 1952.[1] Nematodes causing such zoonotic infections are Baylisascaris procyonis,[2] Toxocara canis,[3] Toxocara cati,[3] and Ascaris suum.[4] These nematodes can infect but not mature in humans and after migrating through the intestinal wall, travel with the blood stream to various organs where they cause inflammation and damage. Affected organs can include the liver, heart (causing myocarditis) and the CNS (causing dysfunction, seizures, and coma). A special variant is ocular larva migrans where usually T. canis larvae travel to the eye.
Only a few roundworm eggs are necessary to cause larva migrans in the human child or adult. However, visceral larva migrans seems to affect children aged 1–4 more often while ocular larva migrans more frequently affects children aged 7–8. Between 4.6% and 23% of U.S. children have been infected with the dog roundworm egg. This number is much higher in other parts of the world, such as Colombia, where up to 81% of children have been infected.[5]
Cutaneous larva migrans is a condition where nematodes such as Ancylostoma braziliense migrate to the skin.
A list of causative agents of larva migrans syndromes is not agreed upon and varies with the author.[6]
## See also[edit]
* Toxocariasis
* Cutaneous larva migrans
## References[edit]
1. ^ Beaver, P. C.; Snyder, C. H.; Carrera, G. M.; Dent, J. H.; Lafferty, J. W. (1952). "Chronic eosinophilia due to visceral larva migrans; report of three cases". Pediatrics. 9 (1): 7–19. PMID 14911260.
2. ^ Gavin, P. J.; Kazacos, K. R.; Shulman, S. T. (2005). "Baylisascariasis". Clinical Microbiology Reviews. 18 (4): 703–18. doi:10.1128/CMR.18.4.703-718.2005. PMC 1265913. PMID 16223954.
3. ^ a b Beaver, PC (1959). "Visceral and cutaneous larva migrans". Public Health Reports. 74 (4): 328–32. doi:10.2307/4590442. JSTOR 4590442. PMC 1929226. PMID 13645880.
4. ^ Sakai, S.; Shida, Y.; Takahashi, N.; Yabuuchi, H.; Soeda, H.; Okafuji, T.; Hatakenaka, M.; Honda, H. (2006). "Pulmonary Lesions Associated with Visceral Larva Migrans Due to Ascaris suum or Toxocara canis: Imaging of Six Cases". American Journal of Roentgenology. 186 (6): 1697–1702. doi:10.2214/AJR.04.1507. PMID 16714661.
5. ^ Artem Cheprasov. 2012. Death at the Playground. Guru Magazine. 11. pp. 59-61.
6. ^ Iowa State University (May 2005). "Larva migrans" (PDF). Retrieved November 10, 2010.
## External links[edit]
Classification
D
* ICD-10: B83.0
* ICD-9-CM: 128.0
* MeSH: D007816
* DiseasesDB: 13882
External resources
* MedlinePlus: 000633
* eMedicine: ped/2407
* v
* t
* e
Parasitic disease caused by helminthiases
Flatworm/
platyhelminth
infection
Fluke/trematode
(Trematode infection)
Blood fluke
* Schistosoma mansoni / S. japonicum / S. mekongi / S. haematobium / S. intercalatum
* Schistosomiasis
* Trichobilharzia regenti
* Swimmer's itch
Liver fluke
* Clonorchis sinensis
* Clonorchiasis
* Dicrocoelium dendriticum / D. hospes
* Dicrocoeliasis
* Fasciola hepatica / F. gigantica
* Fasciolosis
* Opisthorchis viverrini / O. felineus
* Opisthorchiasis
Lung fluke
* Paragonimus westermani / P. kellicotti
* Paragonimiasis
Intestinal fluke
* Fasciolopsis buski
* Fasciolopsiasis
* Metagonimus yokogawai
* Metagonimiasis
* Heterophyes heterophyes
* Heterophyiasis
Cestoda
(Tapeworm infection)
Cyclophyllidea
* Echinococcus granulosus / E. multilocularis
* Echinococcosis
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This infectious disease article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Visceral larva migrans | c0023049 | 3,633 | wikipedia | https://en.wikipedia.org/wiki/Visceral_larva_migrans | 2021-01-18T18:50:30 | {"mesh": ["D007816"], "umls": ["C0023049"], "icd-9": ["128.0"], "icd-10": ["B83.0"], "wikidata": ["Q3288116"]} |
## Description
Myopia, or nearsightedness, is a refractive error of the eye. Light rays from a distant object are focused in front of the retina and those from a near object are focused in the retina; therefore distant objects are blurry and near objects are clear (summary by Kaiser et al., 2004).
For a discussion of genetic heterogeneity of susceptibility to myopia, see 160700.
Mapping
Hammond et al. (2004) undertook a classic twin study of 506 twin pairs, 280 dizygotic (DZ) and 226 monozygotic (MZ), to establish the heritability of refractive error as determined by mean spherical equivalent (SE). The mean SE for the 506 twin pairs was +0.39 diopters (D), with a range of -12.12 D to +7.25 D. Only 4 MZ and 3 DZ twin pairs were well within the high myopia range (greater than -6.00 D). The heritability of refractive error was inferred to be 0.89. To ascertain potential susceptibility loci for myopia, Hammond et al. (2004) performed a genomewide linkage scan for the continuous trait using 221 of the DZ twin pairs. Maximum evidence for linkage was observed at chromosome 11p13 (MYP7; 609256), with a lod score of 6.1. Other linkage peaks were observed at chromosomes 3q26 (MYP8), 4q12 (MYP9; 609258), and 8p23 (MYP10; 609259), with lod scores of 3.7, 3.3, and 4.1, respectively.
INHERITANCE \- Multifactorial HEAD & NECK Eyes \- Myopia, low to moderate (-12.12 D to +7.25 D) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| MYOPIA 8 | c1836505 | 3,634 | omim | https://www.omim.org/entry/609257 | 2019-09-22T16:06:26 | {"mesh": ["C563760"], "omim": ["609257"]} |
## Clinical Features
Marion et al. (1989) observed 7 patients who presented a prematurely aged facial appearance and the following features: intrauterine growth retardation with postnatal growth delay, normal mental development, and decreased subcutaneous fat. The facial appearance included triangular facies, prominent forehead, thin or absent scalp hair, deep-set eyes, midfacial hypoplasia, prominent nasal septum with hypoplasia of the alae nasi, prominent ears, and thin lips.
Inheritance
Marion et al. (1989) suggested autosomal dominant inheritance of this disorder because 3 of the patients were from the same family--2 daughters and their father.
Neuro \- Normal mental development Facies \- Prematurely aged facial appearance \- Triangular facies \- Prominent forehead \- Deep-set eyes \- Midfacial hypoplasia \- Prominent nasal septum \- Hypoplastic alar nasae \- Prominent ears \- Thin lips Inheritance \- Autosomal dominant Hair \- Thin or absent scalp hair Growth \- Intrauterine growth retardation \- Postnatal growth delay Skin \- Decreased subcutaneous fat ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GRANDDAD SYNDROME | c1841836 | 3,635 | omim | https://www.omim.org/entry/138920 | 2019-09-22T16:40:37 | {"mesh": ["C564211"], "omim": ["138920"], "synonyms": ["Alternative titles", "GROWTH RETARDATION, AGED FACIES, NORMAL DEVELOPMENT, DECREASED SUBCUTANEOUS FAT, AUTOSOMAL DOMINANT INHERITANCE"]} |
A rare spotted fever rickettsiosis caused by infection with the tick-borne bacterium Rickettsia conorii, characterized by the onset of fever after an incubation period of about a week, followed by a centripetally spreading maculopapular rash, which may evolve into a petechial form. Accompanying symptoms are headaches, myalgia and/or arthralgia, among others. The typical ''tache noire'' may be observed at the site of the tick bite for several days. The disease is endemic in Africa, Southern Europe, and India.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Boutonneuse fever | c0006060 | 3,636 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=83313 | 2021-01-23T18:40:21 | {"mesh": ["D001907"], "umls": ["C0006060"], "icd-10": ["A77.1"], "synonyms": ["Mediterranean spotted fever"]} |
## Summary
### Clinical characteristics.
GLB1-related disorders comprise two phenotypically distinct lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB).
GM1 gangliosidosis includes phenotypes that range from severe to mild. Type I (infantile) begins before age one year; progressive central nervous system dysfunction leads to spasticity, deafness, blindness, and decerebrate rigidity. Life expectancy is two to three years. Type II can be subdivided into the late-infantile form and juvenile form. Type II, late-infantile form begins between ages one and three years; life expectancy is five to ten years. Type II, juvenile form begins between ages three and ten years with insidious plateauing of motor and cognitive development followed by slow regression. Type II may or may not include skeletal dysplasia. Type III begins in the second to third decade with extrapyramidal signs, gait disturbance, and cardiomyopathy; and can be misidentified as Parkinson disease. Intellectual impairment is common late in the disease; skeletal involvement includes short stature, kyphosis, and scoliosis of varying severity.
MPS IVB is characterized by skeletal changes, including short stature and skeletal dysplasia. Affected children have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years, and the attenuated form in late childhood or adolescence. In addition to skeletal involvement, significant morbidity can result from respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, corneal clouding, and spinal cord compression. Intellect is normal unless spinal cord compression leads to central nervous system compromise.
### Diagnosis/testing.
The diagnosis of GLB1-related disorders is suspected in individuals with characteristic clinical, neuroimaging, radiographic, and biochemical findings. The diagnosis is confirmed by either deficiency of β-galactosidase enzyme activity or biallelic pathogenic variants in GLB1.
### Management.
Treatment of manifestations: Best provided by specialists in biochemical genetics, cardiology, orthopedics, and neurology and therapists knowledgeable about GLB1-related disorders; surgery is best performed in centers with surgeons and anesthesiologists experienced in the care of individuals with lysosomal storage disorders; occupational therapy to optimize activities of daily living (including adaptive equipment) and physical therapy to optimize gait and mobility (including orthotics and bracing); early and ongoing interventions to optimize educational and social outcomes.
For those with GM1 gangliosidosis: Adequate nutrition to maintain growth; speech therapy to optimize oral motor skills; aggressive seizure control; routine management of risk of aspiration, risk of chronic urinary tract infection, and cardiac involvement; when disease is advanced: hospice services for supportive in-home care.
Prevention of secondary complications: Anesthetic precautions to anticipate and manage complications relating to skeletal involvement and airway compromise; routine immunization; bacterial endocarditis prophylaxis in those with cardiac valvular disease.
Surveillance:
* GM1 gangliosidosis: Routine monitoring of growth and nutrition. Assess yearly: quality of life including history and physical examination; seizure risk by a neurologist; cervical spine stability; and hip dislocation risk. Perform every one to three years: electrocardiogram and echocardiogram; eye examination.
* MPS IVB: Yearly: perform endurance tests to evaluate functional status of the cardiovascular, pulmonary, musculoskeletal, and nervous systems; assess lower extremities for malalignment, hips for dysplasia/subluxation, thoracolumbar spine for kyphosis, and cervical spine for instability; perform eye examination and audiogram. Perform electrocardiogram and echocardiogram every one to three years depending on disease course; assess for obstructive sleep apnea and restrictive lung disease; monitor nutritional status using MPS IVA-specific growth charts.
Agents/circumstances to avoid: Psychotropic medications because of the risk of worsening neurologic disease; obesity in those with skeletal dysplasia
### Genetic counseling.
GLB1-related disorders are inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variants in the family have been identified.
## Diagnosis
GLB1-related disorders comprise two phenotypically unique disorders, GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB).
Formal diagnostic criteria have not been established for GLB1-related disorders.
Since MPS IVB is clinically indistinguishable from MPS IVA, it may be appropriate to use the recently published MPS IVA clinical diagnostic criteria as an aid in MPS IVB diagnosis [Wood et al 2013].
### Suggestive Findings
The diagnosis of GLB1-related disorders is suspected in individuals with the clinical, neuroimaging, radiographic, and biochemical findings summarized by phenotype in Table 1 [Regier et al 2016].
### Table 1.
Clinical, Skeletal, Neuroimaging, and Biochemical Findings in GLB1-Related Disorders
View in own window
FindingGM1 GangliosidosisMPS IVB
Type IType IIType III
InfantileLate InfantileJuvenileChronic/Adult
Onset of symptoms<1 yr1-3 yrs3-10 yrs10+ yrs3-5 yrs
Eye findingsCRSCCCC+/– CCCC
Motor abnormalities+++ExtrapyramidalSee footnote 1
Hepatosplenomegaly++/–+/–––
Cardiac involvement+/–+/–+/–+/–+
Coarse facial features+/––––See footnote 1
Skeletal findings++/–+/––+
NeuroimagingPAPAPA+/– mild atrophySee footnote 1
Urine glycosaminoglycans (GAG)See footnote 2See footnote 2See footnote 2See footnote 2Keratan sulfate 3
– = negative finding; + = positive finding; +/ – = variable finding in patient population; CC = corneal clouding; CRS = cherry red spot; PA = progressive atrophy
1\.
Secondary to bony changes
2\.
Oligosaccharide with terminal galactose sugar
3\.
False negative results can be observed.
#### Clinical Findings
GM1 gangliosidosis
* Type I (infantile; onset age <1 year) is the most common phenotype. Infants have macular cherry-red spots, developmental delay followed by regression generally observed by age six months, hepatosplenomegaly, cardiac involvement, coarse facial features, and generalized skeletal dysplasia of varying severity.
* Type II includes:
* Late infantile (onset age 1-3 years). These children typically have corneal clouding (Figure 1), motor abnormalities, and progressive and diffuse atrophy on brain imaging; they may have hepatosplenomegaly, cardiac involvement, and/or skeletal abnormalities.
* Juvenile (onset age 3-10 years). These children typically have motor regression and consistent brain MRI findings of progressive atrophy. Overall, the disease progression is slower than in the late-infantile type.
* Type III (chronic/adult) is the mildest form of the disease spectrum with dystonia leading to gait or speech difficulty as the first symptom.
#### Figure 1.
Image obtained with a slit lamp demonstrating mild to moderate corneal clouding in an adolescent with the juvenile form of GM1 gangliosidosis Picture courtesy of Dr. Wahdi Zein, National Eye Institute, National Institutes of Health, Bethesda, MD
Mucopolysaccharidosis type IVB (MPS IVB) is characterized by corneal clouding, cardiac involvement, severe skeletal abnormalities, and short stature [reviewed in Suzuki et al 2014]. Developmental milestones, cognitive function, and neurologic function are normal unless neurologic complications (e.g., spinal cord impingement) develop secondary to severe skeletal dysplasia [reviewed in Tomatsu et al 2011].
#### Radiographic Findings
GM1 gangliosidosis (Figure 2)
#### Figure 2.
Radiographs of the late infantile form of GM1 gangliosidosis A. The odontoid process is under ossified (white arrow). The vertebral bodies are flattened (black arrow).
* Type I and type II. Findings observed in many, but not all, persons include: dysostosis multiplex with thickened calvaria, J-shaped enlarged sella turcica, hypoplastic/anteriorly beaked thoracolumbar vertebrae, wide spatula-shaped ribs, flared ilia, acetabular dysplasia with flat femoral heads, shortened long bones with diaphyseal widening, pectus carinatum, and/or wide wedge-shaped metacarpals [reviewed in Suzuki et al 2014].
* Type III. Only mild vertebral changes may be observed.
MPS IVB. See Note. Findings on skeletal survey that suggest the diagnosis of MPS IVB include the following:
* Odontoid hypoplasia with subsequent risk for cervical instability
* Kyphosis (curving of the spine that causes a bowing or rounding of the back, which leads to a hunchback or slouching posture)
* Gibbus (structural kyphosis due to wedging of one or more adjacent vertebrae)
* Scoliosis
* Pectus carinatum or excavatum
Note: (1) Based on wide variations and subtleties of the radiographic findings in MPS IV, multiple body regions should be evaluated. (2) While the radiographic findings in MPS IVA (caused by biallelic GALNS pathogenic variants) and MPS IVB are extensive and can be diagnostic, they cannot distinguish MPS IVA from MPS IVB. (See Mucopolysaccharidosis Type IVA for a detailed discussion of the radiographic findings.)
#### Neuroimaging
GM1 gangliosidosis. Brain MRI can show the following:
* Diffuse atrophy and white matter abnormalities
* T2-weighted hypointensity in the basal ganglia/globus pallidus that is not specific (Figure 3).
* In individuals with adult-onset disease: hyperintensity in the putamen and/or mild cerebral atrophy [reviewed in Erol et al 2006, Steenweg et al 2010]
#### Figure 3.
Brain MRI findings in a child with the late infantile form of GM1 gangliosidosis A. At age 3 years 6 months: T2-weighted axial view showing minimal atrophy
Brain MR spectroscopy (MRS) has shown patient-specific changes documented in case reports [Erol et al 2006] and described as a marker of disease progression by Regier et al [2016].
#### Urine Glycosaminoglycans (GAG) Analysis
GM1 gangliosidosis. Although a specific GAG pattern in urine is noted in persons with GM1 gangliosidosis, enzyme activity or molecular genetic testing is necessary for diagnosis [Suzuki et al 2014].
MPS IVB. Excretion of keratan sulfate in the urine can be diagnostic of MPS IV; however, the presence of keratan sulfate in the urine does not distinguish MPS IVA from MPS IVB; thus, additional studies are warranted (see To Confirm/Establish the Diagnosis in a Proband).
A glycosaminoglycan screen can be falsely negative; thus, testing to confirm the diagnosis should be performed if there is clinical suspicion (see To Confirm/Establish the Diagnosis in a Proband).
### To Confirm/Establish the Diagnosis in a Proband
The diagnosis of a GLB1-related disorder in a proband relies on either β-galactosidase enzyme analysis or GLB1 molecular genetic testing. Despite the availability of molecular genetic testing, the mainstay of diagnosis of GLB1-related disorders will likely continue to be enzyme activity because of cost and difficulty in interpreting variants of unknown significance.
β-galactosidase enzyme analysis. The definitive diagnosis of a GLB1-related disorder can be made by measuring β-galactosidase enzyme activity in peripheral blood leukocytes or fibroblasts.
The diagnosis of MPS IVB can be confirmed by the combination of keratan sulfate in the urine and decreased enzyme activity for β-galactosidase enzyme activity in peripheral blood leukocytes or fibroblasts in the absence of intellectual disability.
### Table 2.
β-Galactosidase Enzyme Activity in GLB1-Related Disorders by Phenotype
View in own window
GM1 GangliosidosisMPS IVB
Type IType IIType III
InfantileLate infantileJuvenileChronic/Adult
β-galactosidase
enzyme activity 1, 2Negligible~1%-5%~3%-10%5%-10%2%-12% 3
1\.
Relative values (% of normal activity)
2\.
Although the percent of residual enzyme activity correlates generally with phenotype, it cannot predict the type of GM1 gangliosidosis. The lack of direct correlation between enzyme activity and disease severity may be due to the use of artificial substrates in the in vitro enzyme assay, which may not exactly replicate in vivo enzyme activity with natural substrates. Modifier genes could theoretically alter enzyme activity and, thus, disease severity.
3\.
Santamaria et al [2007]
Note: Enzyme activity may not be predictive of carrier status in family members of individuals with a GLB1-related disorder.
Molecular genetic testing. The definitive diagnosis of a GLB1-related disorder can be made by identification of biallelic pathogenic variants in GLB1 if enzyme analysis is not available and/or results are not definitive (see Table 3).
### Table 3.
Molecular Genetic Testing Used in GLB1-Related Disorders
View in own window
Gene 1MethodVariants Detected 2Variant Detection Frequency by Method 3
GLB1Sequence analysis 4Sequence variants>99% 5
Deletion/duplication analysis 6Exon or whole-gene deletions<1% 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants.
3\.
The ability of the test method used to detect a variant that is present in the indicated gene
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Santamaria et al [2007], Brunetti-Pierri & Scaglia [2008]
6\.
Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
7\.
One individual had a deletion of exon 5 [Santamaria et al 2007]. See Molecular Genetics.
## Clinical Characteristics
### Clinical Description
GLB1-related disorders comprise two phenotypically distinct disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB).
#### GM1 Gangliosidosis
The phenotype of GM1 gangliosidosis constitutes a spectrum ranging from severe (infantile) to intermediate (late infantile and juvenile) to mild (chronic/ adult). Although classification into these types is arbitrary, it is helpful in understanding the variation observed in the timing of disease onset, symptoms, rate of progression, and longevity.
Published natural history studies for GM1 gangliosidosis have been limnited; however, there have been several case reports [Hofer et al 2010, Caciotti et al 2011], including extensive documentation of more than 200 affected individuals [Brunetti-Pierri & Scaglia 2008]. Regier et al [2016] followed juvenile and late-infantile affected individuals and Jarnes Utz et al [2017] described the natural history of affected infants.
Type I (infantile) GM1 gangliosidosis. Onset of symptoms is prior to age 12 months. In some infants prenatal manifestations include hydrops fetalis (6%) and intrauterine growth retardation (1%) [Brunetti-Pierri & Scaglia 2008].
The primary findings are severe central nervous system dysfunction [Suzuki et al 2014] manifest as early developmental delay with hypotonia and an exaggerated startle response, followed by spasticity and rapid regression. By the end of the first year, most infants are blind and deaf with severe central nervous system dysfunction leading to decerebrate rigidity [Suzuki et al 2014].
Cardiomyopathy and seizures are common. Some infants manifest hepatosplenomegaly and poor feeding.
Other findings include a coarsened facial appearance (often including frontal bossing, depressed nasal bridge with a broad nasal tip, long philtrum), large low-set ears, gingival hypertrophy with macroglossia, coarse thickened skin, and hirsutism.
Skeletal dysplasia can be seen at the time of diagnosis and may become clinically important over time.
Disease progression is rapid with blindness often by age one year and death by age two to three years frequently secondary to aspiration pneumonia.
Type II (late infantile and juvenile) GM1 gangliosidosis
* The onset of the late infantile form is typically between ages one and three years with life expectancy until ages five to ten years.
* The onset of the juvenile form is typically between ages three and ten years and often initially manifests in a school-age child as inability to achieve expected milestones. Disease progression is notable for plateauing of motor and cognitive development followed by slow regression of skills. The juvenile form may or may not have skeletal dysplasia. Life expectancy is well into the second decade.
Chronic/adult GM1 gangliosidosis has been best characterized in the Japanese population. Onset of symptoms is in late childhood to the third decade [Suzuki et al 2014], typically presenting with generalized dystonia leading to unsteady gait and speech disturbance. However, within a short period of time, most (64%) have extrapyramidal signs including akinetic-rigid parkinsonism. The symptom cluster is similar to the extrapyramidal signs in Parkinson disease, which is a common misdiagnosis [Roze et al 2005]. Other common findings are: gait disturbance (44%), cardiomyopathy (38%), speech difficulties (33%), and dystonia (22%) [Suzuki et al 2014].
Although intellectual impairment is common in late stages of the disease, it may be only mild at time of initial diagnosis.
Skeletal abnormalities, found in 95% of individuals, are most commonly short stature, kyphosis, and scoliosis of varying severity.
Prognosis is directly related to the degree of neurologic impairment. Most affected individuals have a shortened life span compared to their unaffected relatives [Suzuki et al 2014].
Neuropathology. All individuals with GM1 gangliosidosis have post-mortem neural changes; specifically, meganeurites and ectopic dendritogenesis have been observed. The extent of ganglioside deposition correlates with age of onset and rate of disease progression [Steenweg et al 2010].
#### Mucopolysaccharidosis Type IVB
MPS IVB is clinically indistinguishable from MPS IVA. Prior to the availability of molecular testing, natural history studies of MPS IV included both MPS IVA (>95% of affected individuals) and MPS IVB (<5% of affected individuals). The following information is relevant to both MPS IVA and MPS IVB.
MPS IV is characterized by corneal clouding, cardiac valvular disease, and skeletal abnormalities, including short stature. In general, neurologic function is normal. Affected children have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years. The attenuated form may not become evident until late childhood or adolescence [Montaño et al 2007].
The initial presentation in both severe and attenuated MPS IV can vary. Kyphoscoliosis, knocked knees (genu valgum), and pectus carinatum are the most common initial manifestations of the severe form [Montaño et al 2007]. In contrast, hip problems including pain, stiffness, and Legg-Perthes disease are common initial manifestations of the attenuated form [Hecht et al 1984, Wraith 1995].
While the skeletal changes in MPS IV are the hallmark findings, involvement of other organ systems can lead to significant morbidity, including respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, corneal clouding, dental abnormalities, and hepatomegaly.
Spinal cord compression can result in neurologic compromise, especially in persons with severe disease or delayed diagnosis [reviewed in Neufeld & Muenzer 2001, Tomatsu et al 2011].
Coarse facial features can develop later in life, but the changes are milder than those observed in other mucopolysaccharidoses (see Differential Diagnosis).
Children with MPS IV typically have normal intellectual ability. Ligamentous laxity and joint hypermobility are distinctive features of MPS IV, and are rare among storage disorders.
### Pathophysiology
GM1 gangliosidosis is caused by pathogenic variants in GLB1 leading to decreased activity of β-galactosidase, a lysosomal enzyme involved in the metabolism of the sphingolipid GM1 ganglioside. When enzyme activity is decreased, sphingolipid intermediates accumulate in the lysosome and, thus, interfere with appropriate functioning of the organelle. A hallmark of GM1 gangliosidosis is degeneration of the CNS where ganglioside synthesis is the highest.
GLB1 pathogenic variants leading to MPS IVB result in the accumulation of keratan sulfate, the suspected causative agent for the bone findings in MPS IVB. Note: In MPS IVA (caused by biallelic GALNS pathogenic variants) and MPS IVB (caused by biallelic GLB1 pathogenic variants), keratan sulfate accumulation is thought to be the cause of severe skeletal abnormalities.
### Genotype-Phenotype Correlations
GM1 gangliosidosis. More than 150 GLB1 pathogenic variants have been found in GM1 gangliosidosis. Common variants have been identified for each subtype; however, since the vast majority of affected individuals are compound heterozygotes, the same pathogenic variants have been identified in more than one phenotype [Santamaria et al 2007; Caciotti et al 2011; Author, unpublished results], making phenotype/genotype correlation difficult [reviewed in Higaki et al 2011]. Ou et al [2019] have recently published a genotype-phenotype in silico tool that has been helpful in the prediction of disease severity.
Current structure/enzyme activity studies indicate that GM1 gangliosidosis is caused by GLB1 pathogenic variants that result in impaired function of the β-galactosidase enzyme towards its high affinity substrate, the glycosphingolipid GM1 ganglioside. In contrast, specific GLB1 variants that cause MPS IVB are proposed to affect the catabolism of keratan sulfate but have little effect on GM1 gangliosides [reviewed in Suzuki et al 2014].
Mucopolysaccharidosis type IVB. Unique pathogenic variants have been found in MPS IVB. Based on the crystal structure, most of these variants map to the surface or protein core of the enzyme [Ohto et al 2012], likely stabilizing the secondary, tertiary, and/or quaternary structure. However, two MPS IVB common variants are located in the ligand binding pocket.
### Nomenclature
In the past GM1 gangliosidosis was referred to as beta-galactosidase-1 deficiency or beta-galactosidosis; mucopolysaccharidosis type IVB was referred to as Morquio syndrome type B. These terms should be used when searching for older literature on GM1 gangliosidosis.
### Prevalence
GM1 gangliosidosis of all types is estimated to occur in one in 100,000 to 300,000 [Suzuki et al 2014]. The most common is the infantile form. The prevalence in Brazil (1:17,000), in persons of Roma ancestry (1:10,000), and in the Maltese Islands (1:3,700) is much higher than in other areas and likely represents founder effects [reviewed in Brunetti-Pierri & Scaglia 2008].
The prevalence of chronic/adult GM1 gangliosidosis is higher in the Japanese population, likely due both to a founder effect and possibly a greater awareness of the disorder among Japanese healthcare providers [Higaki et al 2011].
MPS IVB. Prior to 1980, MPS IVA and IVB were indistinguishable. The overall prevalence of MPS IV was reported as 1:75,000 to 1:640,000 [reviewed in Ohto et al 2012]. Subsequently the prevalence of MPS IVB has been reported as 1:250,000-1:1,000,000 [Baehner et al 2005, Enns et al 2009].
## Differential Diagnosis
Disorders to consider in the differential diagnosis of the GLB1-related disorders include the following.
### MPS IVB
Mucopolysaccharidosis IVA (MPS IVA) and MPS IVB are clinically indistinguishable. Of individuals with the MPS IV phenotype, MPS IVA accounts for more than 95% of affected individuals and MPS IVB accounts for fewer than 5% of affected individuals. The diagnosis of MPS IVA is confirmed by detection either of deficient N-acetylgalactosamine 6-sulfatase (GALNS) enzyme activity or of biallelic GALNS pathogenic variants.
### GM1 Gangliosidosis
GM2 gangliosidosis (also known as hexosaminidase A deficiency) also presents similarly with a range of severity, including infantile, juvenile, and adult forms. Onset of CNS symptoms in GM1 and GM2 gangliosidosis is similar between each of the forms. The infantile forms of both disorders feature cherry red maculae. However, individuals with GM2 gangliosidosis do not have skeletal changes or other non-CNS findings.
Galactosialidosis and sialidosis (mucolipidosis I) need to be considered in the differential diagnosis of GM1 gangliosidosis. Galactosialidosis and sialidosis are caused by deficiencies in enzymes that form a complex with β-galactosidase. This high molecular-weight complex includes β-galactosidase (GM1 gangliosidosis), cathepsin A encoded by CTSA (galactosialidosis), and neuramidase 1 encoded by NEU1 (sialidosis/mucolipidosis I). Note that in galactosialidosis the activities of the enzymes β-galactosidase and neuramidase 1 are reduced, respectively, to about 15% and less than 1% of normal values secondary to a primary deficiency of the protective protein/cathepsin A. Therefore, the activities of cathepsin A and neuraminidase 1 in fibroblasts should be measured to definitively rule out galactosialidosis in an individual with partial deficiency of β-galactosidase.
Galactosialidosis. Three forms are distinguished by the age of onset and disease course.
* Early-infantile galactosialidosis is associated with hydrops fetalis, inguinal hernia, growth abnormality, and hepatosplenomegaly. Dysostosis multiplex, coarse facial features, corneal clouding, cardiomegaly, cherry-red spot of the macula, and kidney failure are also common. Angiokeratomas have been observed. Affected infants typically die by age one year.
* Late-infantile galactosialidosis is associated with short stature, dysostosis multiplex, cardiac valvulopathy, hepatosplenomegaly, intellectual disability, and coarse facial features. Cherry-red spot of the macula, angiokeratomas, corneal clouding, and hearing loss can be observed. Life expectancy depends on disease severity.
* Juvenile/adult galactosialidosis is associated with a variable age of onset (average 16 years, range 1-40 years). Symptoms include ataxia, myoclonus, seizures, corneal clouding, and progressive intellectual disability. Angiokeratomas, spine abnormalities, cherry red spot of the macula, and vision and hearing loss are common. Life expectancy varies. The highest prevalence has been noted in the Japanese population.
Sialidosis (mucolipidosis I). Accumulation of sialylated oligo- and polysaccharides in tissues and body fluids are likely the cause of widespread cellular damage. Two forms determined by the level of neuramidase I enzyme activity have been identified. The features of sialidosis II more closely resemble GM1 gangliosidosis than sialidosis I.
* Both sialidosis type II and GM1 gangliosidosis have a range of severity from congenital to juvenile onset. All have dysostosis multiplex, cherry red spot of the macula, and intellectual disability.
* The congenital form has prenatal onset with ascites or hydrops fetalis.
* The infantile form has onset in the first year of life with hepatosplenomegaly, developmental regression, and coarse facial features. Over time, affected children can have myoclonus, hearing loss, gingival hyperplasia, and abnormal spacing of the dentition. Life expectancy is into childhood or adolescence.
* The juvenile form has onset in late childhood. Coarse facial features, myoclonus, and angiokeratomas are observed. Life expectancy is symptom-dependent with more mildly affected individuals living into adulthood.
* Sialidosis type I is also known as cherry-red spot myoclonus syndrome. Onset is in the teens and twenties. Gait disturbances and reduced visual acuity are the most common presenting symptoms. With time, myoclonus, ataxia, and reduced vision worsen, but are not life threatening. Intellect is normal.
Mucopolysaccharidosis type I (MPS I). Dysostosis multiplex and corneal clouding are seen in both MPS I and GLB1-related disorders; however, MPS I has more severe dysostosis multiplex, contractures, and prominent hepatosplenomegaly and does not have cherry red spot of the macula.
Mucopolysaccharidosis type II (MPS II). Children with MPS II have developmental delay and dysostosis multiplex, also seen in the juvenile form of GM1 gangliosidosis. At the time of diagnosis, prominent hepatosplenomegaly, joint contractures, dermal pebbling, clear corneae, and a coarse facial appearance distinguish MPS II from GLB1-realated disorders. Furthermore, MPS II, an X-linked disorder, is observed in males only, whereas GM1 gangliosidosis, an autosomal recessive disorder, is observed in males and females.
Mucolipidoses
* Mucolipidosis II (ML II) (I-cell disease) includes skeletal dysplasia, global developmental delay, and growth abnormalities similar to GM1 gangliosidosis type I. ML II has more severe and earlier onset skeletal dysplasia than GM1 gangliosidosis. ML II can present prenatally with low birth weight or in the neonatal period with skeletal dysplasia, global development delay, and coarse facial features. In comparison, children with GM1 gangliosidosis can be normal as neonates and present in early infancy.
* Mucolipidosis III (both mucolipidosis III alpha/beta and mucolipidosis III γ) (pseudo-Hurler polydystrophy) includes onset of clinical features in the preschool years (corneal clouding, cardiac valvular abnormalities, developmental delay, dysostosis multiplex) similar to those observed in the juvenile form of GM1 gangliosidosis. In contrast with GM1 gangliosidosis, ML III usually presents with hand and shoulder arthritis, significant short stature, and/or claw hand deformity.
The differential diagnosis of chronic/adult GM1 gangliosidosis includes Parkinson disease, adult-onset spinal muscular atrophy, spinal cerebellar ataxia, adult-onset GM2 gangliosidosis, juvenile Huntington disease, and Wilson disease.
Note: Positive testing for anti-GM1 ganglioside antibodies is not indicative of a diagnosis of GM1 gangliosidosis. These test results are associated with multifocal motor neuropathy or Guillain-Barré syndrome [reviewed in Kornberg 2000].
## Management
Management in GM1 gangliosidosis is an emerging field. In 2017, Deodato et al [2017] published a small case series (2 juveniles and 1 adult) showing improved ambulation with miglustat treatment of 600 mg/day. Jarnes Utz et al [2017] reported a series of eight infants treated with a combination of miglustat and ketogenic diet. A small increase in life expectancy was reported. However, the authors also commented on the severity of gastrointestinal side effects. Thus, it is important to consider the gastrointestinal side effects of this treatment and quality of life when creating a treatment plan for infants.
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with a GLB1-related disorder (GM1 gangliosidosis or MPS IVB), the following evaluations are recommended:
* Developmental history and assessment to document past and current motor and cognitive function, as a baseline in the event of future psychomotor and/or cognitive regression
* Physical examination for evidence of hepatosplenomegaly
* Ophthalmologic examination, especially for evidence of corneal clouding and cherry red spot of the macula
* Evaluation by a pediatric cardiologist (including electrocardiogram and echocardiogram) to assess for cardiac involvement
* Skeletal survey to determine the extent of skeletal involvement
* Flexion and extension x-rays of the cervical spine to assess for atlanto-axial instability
* Electroencephalogram to assess for seizure disorder, if indicated
* Clinical genetics consultation with genetic counseling
### Treatment of Manifestations
Treatment and quality of life can be optimized when care is provided by specialists in biochemical genetics, cardiology, orthopedics, and neurology, and therapists knowledgeable about GLB1-related disorders.
* Surgery is best performed in centers with surgeons and anesthesiologists experienced in the care of individuals with lysosomal storage disorders.
* Occupational therapy to optimize activities of daily living (including adaptive equipment)
* Physical therapy to optimize gait, comfort, and mobility including orthotics and bracing to improve mobility and flexibility
* Early and ongoing interventions to optimize educational and social outcomes are recommended.
GM1 gangliosidosis
* For patients with GM1 gangliosidosis type I or II, physiatry for appropriate mobility interventions, such as strollers and wheelchairs
* Speech therapy to optimize oral motor skills and manage aspiration risk
* Maintenance of adequate hydration and adequate calories for growth. Consider gastrostomy (G-) tube or naso-gastric (NG) tube placement as needed.
* Routine management of secretions and risk of aspiration with attention to risk for pulmonary sequelae
* Routine management of chronic urinary tract infections secondary to incontinence and chronic dehydration
* Aggressive seizure control
* Medical management of cardiac involvement
* When disease is advanced, provide access to hospice services for supportive in-home care
MPS IVB. Since MPS IVA and IVB are clinically indistinguishable, details of interventions are based on those recommended for MPS in general or specifically MPS IVA.
### Prevention of Secondary Complications
Immunizations. All individuals with GLB1-related disorders should receive routine immunizations. Influenza and pneumococcal immunizations should be administered on schedule because of the low pulmonary reserve of individuals with MPS IVB and the risk for secondary infections due to chronic disease in children with GM1 gangliosidosis.
Bacterial endocarditis prophylaxis is recommended for all high-risk patients, including those with a prosthetic cardiac valve, prosthetic material used for cardiac valve repair, or previous infective endocarditis [Wilson et al 2007].
Anesthesia. Because children with MPS IVB and those with GM1 gangliosidosis with skeletal involvement (spine anomalies, short neck, large head, and atlantoaxial instability) are at increased risk for complications of anesthesia, the following are recommended [Walker et al 2013]:
* Preoperative evaluation should include a history of complications with previous anesthetics, as well as any ongoing problems with airway obstruction, the heart, and respiratory function.
* Obtain flexion/extension x-rays of the lateral cervical spine [Muhlebach et al 2011; Tomatsu et al 2011; Author, unpublished observations].
* Fiber-optic bronchoscopy and smaller than expected endotracheal tubes are often required [Muhlebach et al 2011].
* For procedures lasting greater than 45 minutes, intraoperative spinal cord monitoring may be necessary to detect exacerbation of pre-existing spinal stenosis.
* Post-operative management may be complicated by pre-existing sleep apnea and/or pulmonary edema [Morgan et al 2002].
### Surveillance
#### GM1 Gangliosidosis
Assessment of quality of life by a physiotherapist; yearly and before/after major medical events
Musculoskeletal
* Yearly history and physical examination to evaluate for new skeletal abnormalities that might lead to decreased quality of life
* Yearly evaluation for cervical spine instability including detailed physical examination and assessment for new neurologic findings, followed by imaging if indicated
* Monitoring of hip joint stability re risk of hip dislocation. Obtain straight and frog-leg imaging if there is pain with movement or a change in mobility (which in neurologically compromised patients can present as inability to ambulate, unexplained crying, or pain).
Cardiac. Electrocardiogram and echocardiogram every one to three years, if there is a history of cardiac dysfunction and/or new symptoms
Growth. Monitoring of growth and nutrition by a nutritionist with knowledge of neurodegenerative or metabolic disease
Eye. Evaluation for visual acuity and corneal clouding every 1-3 years
Seizures. Yearly evaluation by a neurologist; consideration of EEG if there is an acute change in mental status, a sudden decline in activity/milestones, or abnormal movements
#### MPS IVB
Note: The recommendations for MPS IVA are appropriate for MPS IVB since MPS IVA and MPS IVB are clinically indistinguishable.
Assessment of quality of life by a physiotherapist:
* Yearly: track progress and optimize ambulation
* Yearly, before and after surgical procedures, and as clinically indicated: endurance tests including six-minute walk test (6MWT) and three-minute stair climb test (3MSC) to evaluate functional status of the cardiovascular, pulmonary, musculoskeletal and nervous systems
Musculoskeletal. Assessment for the following:
* Lower-extremity misalignment: yearly clinical examinations to assess lower extremity alignment
* Hip dysplasia/subluxation: yearly radiographs of the hips, as clinically warranted
* Cervical spine instability
* Note: Solanki et al [2013] recommend the following guidelines for monitoring spinal involvement in those with MPS IVA:
* Neurologic examination every six months
* Plain x-rays of the cervical spine (AP, lateral, neutral, and flexion/extension) every six months
* Plain x-rays of the spine (AP and lateral thoracolumbar) every two to three years if there is evidence of kyphosis and/or scoliosis
* MRI neutral position: whole spine every year
* MRI: flexion/extension of the cervical spine every one to three years
These guidelines can be modified as appropriate.
Cardiac. Electrocardiogram and echocardiogram every one to three years depending on disease course [Hendriksz et al 2013]
Respiratory. Assessment for the following:
* Obstructive sleep apnea: yearly history focused on sleep patterns and sounds. Evaluation by an otolaryngologist for adenotonsillectomy. Polysomnography if any clinical suspicion exists.
* Restrictive lung disease: assessment of pulmonary function when age-appropriate at diagnosis and then yearly. Note: The benefit of noninvasive pulmonary function tests, impulse oscillometry, and thoracoabdominal motion analysis has been demonstrated in children with MPS IV [Rodriguez et al 2010].
Growth. Use of MPS IVA-specific growth charts to monitor nutritional status [Montaño et al 2007, Montaño et al 2008]
Eye
* Yearly: measurement of visual acuity, refractive error, and intraocular pressure; slit lamp examination of cornea; examination of the posterior segment
* For those with rod and cone retinal dystrophy: Retinal examination and electroretinography (ERG) under scotopic and photopic conditions at onset, then every five years [Hendriksz et al 2013]
Dental. Evaluation every six months
Hearing. Yearly audiogram
### Agents/Circumstances to Avoid
Because psychotropic medications have been associated with worsening neurologic disease in adults with Tay-Sachs disease (which is caused by deficiency of the second enzyme in the β-galactosidase pathway) [Shapiro et al 2006], use of these medications in individuals with a GLB1-related disorder should be avoided whenever possible [Shapiro et al 2006].
For persons with MPS IVB, excessive weight gain causes undue stress on the axial skeleton and may decrease the ability to ambulate independently. Thus, it is important that nutrition optimize growth while maintaining a lean habitus.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
No FDA-approved treatments for GLB1-related disorders exist.
While there is currently no effective treatment for GM1 gangliosidosis, multiple interventions are promising, based on in vitro studies and animal models.
Although many lysosomal storage diseases have positive outcomes with hematopoietic stem cell transplantation (HSCT), in one individual with the juvenile form of GM1 gangliosidosis diagnosed prior to onset of symptoms, HSCT did not prevent the development of manifestations. This failure was attributed to the inability of sufficient stem cells to cross the blood-brain barrier rapidly enough to affect lipid accumulation in the central nervous system (CNS) [Shield et al 2005].
Due to the inability of large molecular-weight enzymes to cross the blood-brain barrier, investigators have been studying small molecules as possible chaperones for partially functioning β-galactosidase in the CNS. These chaperones are thought to stabilize the residual endogenous enzyme and facilitate transport to the lysosome.
* In an in vitro study using fibroblasts from an affected individual, N-octyl-4-epi-B-valienamine stabilized β-galactosidase, reduced lipid accumulations, and improved lipid trafficking [Higaki et al 2011]. Furthermore, oral administration of this compound to mice with GM1 gangliosidosis led to increased enzyme activity and reduced substrate levels [reviewed in Brunetti-Pierri & Scaglia 2008].
* A second chaperone compound, the imino sugar N-butyl deoxynojirimycin (miglustat), also showed promising outcomes in a murine model of GM1 gangliosidosis [Elliot-Smith et al 2008]. Miglustat, which is FDA approved for the treatment of Gaucher disease, has been used in a few individuals with the juvenile form of GM1 gangliosidosis of whom some showed improvement [Author, unpublished observation].
* In addition, other imino sugar derivatives have shown increased enzyme activity, facilitated localization of β-galactosidase to lysosomes in fibroblasts of affected individuals [Fantur et al 2012], and shown improved enzyme activity in a mouse model of GM1 gangliosidosis [Takai et al 2013].
Intravenous gene therapy with an AAV9-GLB1 vector is currently in clinical trials for GM1 gangliosidosis (NCT03952637).
Considerable progress has been made in gene therapy in a murine model of GM1 gangliosidosis. See animal model.
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GLB1-Related Disorders | None | 3,637 | gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK164500/ | 2021-01-18T21:24:43 | {"synonyms": []} |
This disease is characterised by progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter.
## Epidemiology
So far, 38 cases have been reported.
## Clinical description
Onset occurs in early childhood. Epilepsy and cognitive decline have also been described.
## Etiology
The syndrome is caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase.
## Diagnostic methods
MRI reveals inhomogeneous periventricular and deep white matter anomalies, with involvement of the cerebellar connections, the entire length of the pyramidal and sensory tracts.
## Genetic counseling
Transmission is autosomal recessive.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome | c1970180 | 3,638 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=137898 | 2021-01-23T18:15:03 | {"gard": ["12652"], "mesh": ["C567009"], "omim": ["611105"], "umls": ["C1970180"], "icd-10": ["E75.2"], "synonyms": ["LBSL", "Leukoencephalopathy with brain stem and spinal cord involvement-lactate elevation syndrome"]} |
Pneumaturia
Emphysematous cystitis in computertomography
SpecialtyUrology
Pneumaturia is the passage of gas or "air" in urine. This may be seen or described as "bubbles in the urine".
## Contents
* 1 Causes
* 2 Diagnosis
* 3 References
* 4 External links
## Causes[edit]
A common cause of pneumaturia is colovesical fistula (communication between the colon and bladder). These may occur as a complication of diverticular disease. Pneumaturia can also happen if a urinary catheter was recently in the bladder.
Other key differentials:
* Crohn's disease
* Carcinoma of the colon or bladder
* A gas-producing UTI (emphysematous cystitis: rare).
* Emphysematous pyelonephritis.
Male scuba divers utilizing condom catheters or female divers using a She-p external catching device for their dry suits are also susceptible to pneumaturia.[1]
## Diagnosis[edit]
Diagnosis is made by patient history of passing air or a sputtering urine stream. CT scans may show air in the urinary bladder or bladder walls.
## References[edit]
1. ^ Harris, Richard (December 2009). "Genitourinary infection and barotrauma as complications of 'P-valve' use in drysuit divers". Diving and Hyperbaric Medicine. 39 (4): 210–2. PMID 22752741. Archived from the original on 2013-05-26. Retrieved 2013-04-04.
## External links[edit]
Classification
D
* DiseasesDB: 30912
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
This medical symptom article is a stub. You can help Wikipedia by expanding it.
* v
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* e
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*[AA]: Adrenergic agonist
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*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
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*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pneumaturia | c0232894 | 3,639 | wikipedia | https://en.wikipedia.org/wiki/Pneumaturia | 2021-01-18T18:31:06 | {"umls": ["C0232894"], "wikidata": ["Q2099998"]} |
A number sign (#) is used with this entry because of evidence that geleophysic dysplasia-2 (GPHYSD2) is caused by heterozygous mutation in exon 41 or 42 of the FBN1 gene (134797) on chromosome 15q21.1.
Acromicric dysplasia (ACMICD; 102370) and the autosomal dominant form of Weill-Marchesani syndrome (608328) are allelic to geleophysic dysplasia-2 and share overlapping skeletal and joint features.
For a general phenotypic description and discussion of genetic heterogeneity of geleophysic dysplasia, see 231050.
Molecular Genetics
In 19 patients with geleophysic dysplasia who were known to be negative for mutation in the ADAMTSL2 gene (612277), Le Goff et al. (2011) performed exome sequencing followed by candidate gene analysis and identified heterozygosity for 8 different mutations in the FBN1 gene (see, e.g., 134797.0055-134797.0058). Two of the mutations were also found in heterozygosity in patients with acromicric dysplasia, a disorder also characterized by short stature, short hands and feet, joint limitations, and skin thickening, but without cardiac involvement or early death. Le Goff et al. (2011) concluded that geleophysic dysplasia and acromicric dysplasia are clinically distinct but allelic conditions.
Passarge et al. (2016) stated that all FBN1 mutations resulting in GPHYSD2 or ACMICD have been found in exon 41 or 42. These exons encode the TGF-beta-binding protein-like domain-5 (TB5) (Le Goff et al., 2011).
INHERITANCE \- Autosomal dominant GROWTH Height \- Short stature HEAD & NECK Face \- 'Happy' face \- Full cheeks \- Long philtrum \- Flat philtrum Eyes \- Hypertelorism Nose \- Shortened nose Mouth \- Thin upper lip CARDIOVASCULAR Heart \- Valvular thickening, progressive \- Mitral valve stenosis \- Mitral valve insufficiency \- Mitral valve prolapse \- Tricuspid valve stenosis \- Aortic valve stenosis \- Aortic valve insufficiency Vascular \- Pulmonary artery hypertension RESPIRATORY Larynx \- Laryngeal stenosis or insufficiency Lung \- Respiratory insufficiency ABDOMEN Liver \- Hepatomegaly SKELETAL \- Delayed bone age \- Decreased joint mobility \- Joint stiffness Spine \- Ovoid vertebral bodies Limbs \- Cone-shaped epiphyses \- Short long tubular bones Hands \- Short hands Feet \- Short feet \- Toe walking SKIN, NAILS, & HAIR Skin \- Thick skin LABORATORY ABNORMALITIES \- Lysosomal-like storage vacuoles in various tissues MISCELLANEOUS \- Early death in some patients due to cardiorespiratory involvement MOLECULAR BASIS \- Caused by mutation in the fibrillin 1 gene (FBN1, 134797.0055 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| GELEOPHYSIC DYSPLASIA 2 | c3489726 | 3,640 | omim | https://www.omim.org/entry/614185 | 2019-09-22T15:56:13 | {"mesh": ["C535662"], "omim": ["614185"], "orphanet": ["2623"], "genereviews": ["NBK11168"]} |
A rare disorder characterized by neurological dysfunction, hepatic failure and cardiomyopathy due to a deficiency of complex I of the respiratory chain.
## Epidemiology
The prevalence is unknown.
## Clinical description
Patients present predominantly with neurological, hepatic and /or cardiomyopathic disease with isolated NADH-CoQ reductase deficiency (see this term). Manifestations include failure to thrive, hypertrophic cardiomyopathy, exercise intolerance, liver disease and mild to severe neurological dysfunction.
## Etiology
ACAD9 deficiency is caused by a mutation in the ACAD9 gene (3q21.3) that encodes the protein ACAD9. This protein has only relatively recently been described but is quite widely expressed in tissues and has activity as an acyl-CoA dehydrogenase with overlapping substrate specificity with very long-chain acyl-CoA dehydrogenase (VLCAD). It also acts an assembly factor for complex I of the respiratory chain and therefore has a vital role in the production of a functioning mitochondrial respiratory chain.
## Genetic counseling
The mode of inheritance is autosomal recessive and genetic counseling is possible.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Acyl-CoA dehydrogenase 9 deficiency | c1970173 | 3,641 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99901 | 2021-01-23T18:56:12 | {"mesh": ["C567006"], "omim": ["611126"], "umls": ["C1970173"], "icd-10": ["E71.3"], "synonyms": ["ACAD9 deficiency"]} |
Iminoglycinuria
Other namesFamilial iminoglycinuria[1][2][3]
Imine, a functional group found in imino acids
SpecialtyEndocrinology
Iminoglycinuria, is an autosomal recessive[4] disorder of renal tubular transport affecting reabsorption of the amino acid glycine, and the imino acids proline and hydroxyproline.[4][5] This results in excess urinary excretion of all three acids (-uria denotes "in the urine").[6]
Iminoglycinuria is a rare and complex disorder, associated with a number of genetic mutations that cause defects in both renal and intestinal transport systems of glycine and imino acids.[4][7][8][9]
Imino acids typically contain an imine functional group, instead of the amino group found in amino acids. Proline is considered and usually referred to as an amino acid,[10][11] but unlike others, it has a secondary amine. This feature, unique to proline, identifies proline also as an imino acid.[12][13] Hydroxyproline is another imino acid, made from the naturally occurring hydroxylation of proline.[12]
## Contents
* 1 Presentation
* 2 Genetics
* 3 Pathophysiology
* 3.1 Mechanism
* 4 Diagnosis
* 5 Treament
* 6 See also
* 7 References
* 8 External links
## Presentation[edit]
The primary characteristic of iminoglycinuria is the presence of glycine and imino acids in the urine. Otherwise, it is thought to be a relatively benign disorder,[6][14] although symptoms associated with disruptions of proline and glycine metabolism caused by malabsorption may be present with iminoglycinuria.[4][15] These include encephalopathy, mental retardation,[2] deafness,[3] blindness,[16] kidney stones,[17] hypertension[18] and gyrate atrophy.[19]
Gyrate atrophy is an inherited degenerative disorder of the retina and choroid,[20] sometimes accompanying the metabolic condition hyperornithinemia.[19][21] The presence of gyrate atrophy with iminoglycinuria stems from a deficiency of proline in chorioretinal tissues, while processes behind hyperornithinemia disrupt the metabolic pathway from ornithine to proline, which alters the catabolism of ornithine, and also results in reduced levels of proline. Thus, gyrate atrophy can be found with either disorder, with proline deficiency as an underlying feature.[19][22]
Hyperglycinuria is another disorder affecting reabsorption of glycine and imino acids, similar to iminoglycinuria and considered to be a heterozygous form.[3][4] When accompanied by a specific type of kidney stone (nephrolithiasis), it is sometimes referred to as "iminoglycinuria, type II".[15][23][24]
## Genetics[edit]
Iminoglycinuria has an autosomal recessive pattern of inheritance.
Iminoglycinuria is believed to be inherited in an autosomal recessive manner.[4] This means a defective gene responsible for the disorder is located on an autosome, and inheritance requires two copies of the defective gene—one from each parent. Parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed]
A non-inherited cause of excess urinary excretion of proline and glycine, similar to that found in iminoglycinuria, is quite common to newborn infants younger than 6 months. Sometimes referred to as neonatal iminoglycinuria, it is due to underdevelopment of high-affinity transport mechanisms within the renal circuit, specifically PAT2, SIT1 and SLC6A18. The condition corrects itself with age.[4][25] In cases where this persists beyond childhood, however, inherited hyperglycinuria or iminoglycinuria may be suspected.[4]
## Pathophysiology[edit]
Glycine, proline and hydroxyproline share common renal tubular mechanisms of reabsorption,[7] a function specific to the proximal tubule.[4][5] Both reabsorption or absorption of glycine and imino acids takes place respectively at the proximal tubule or intestinal brush border epithelium. The more selective transport of proline and other imino acids is driven at the molecular level by a mammalian cellular transport mechanism aptly known as system IMINO.[5][26][27]
Active transport into a cell through ion channels, using the coupling power provided by sodium-potassium exchange.
While no single genetic mutation has been established as the cause of iminoglycinuria; several mutations, affecting transport mechanisms shared by glycine, proline and hydroxyproline, as well as those that selectively transport either glycine or imino acids, including the IMINO system, are known to be associated with the disorder.[4] When combined, these factors will result in a variable phenotype for iminoglycinuria depending on which mutations are present.[4] However, despite the role that intestinal malabsorption of glycine and imino acids can play in iminoglycinuria, the primary defect disrupts their renal transport and reabsorption.[4][14] This is evident, as inherited iminoglycinuria can be clinically present with no intestinal involvement.[16]
In mammals, including humans, the transport of amino and imino acids from the lumen (interior) of the intestine or the renal proximal tubule into the cells occurs at the brush border membrane of the epithelium (moist, tightly packed cellular lining of many tissues and organs of the body). Here, cotransporters such as sodium or chloride (part of the system of Na-K-Cl cotransporters) couple with the amino or imino acids on the molecular level and transport them through specific integral membrane proteins that form ion channels, which are located within the cell membrane.[27][28] From the cells, the absorbed or reabsorbed amino and imino acids eventually reach the blood. Absorption refers to the overall process happening in the intestine in lieu of normal digestive breakdown of proteins, while reabsorption refers to the process occurring in the renal proximal tubule to reclaim amino and imino acids that have been filtered out of the blood via the glomerulus.[citation needed]
These forms of transport require energy, as the products being transported are usually moving against a higher concentration gradient. This process, called active transport, get its energy from ATP and other ATP-related cotransport systems that produce energy, like the sodium-potassium pump.[citation needed]
### Mechanism[edit]
The primary defect associated with iminoglycinuria is a homozygous (recessive) mutation of the SLC36A2 (PAT2) gene.[4] One of several membrane transport proteins in the solute carrier family of amino acid transporters, PAT2 is the high-affinity renal transporter of glycine, proline and hydroxyproline found to be defective in both alleles when iminoglycinuria is present in an individual. This is in contrast to the fact that when only one PAT2 allele is defective, hyperglycinuria will be present instead of iminoglycinuria. These findings delineate iminoglycinuria as the homozygous form of hyperglycinuria, with the former having a higher degree of urinary excretion of glycine and imino acids correlating to mutations in both alleles.[4][7]
Another mutation suspected to convey the iminoglycinuria phenotype may be found in the SLC36A1 (PAT1) gene.[29][30] Identified as the low-affinity intestinal transporter of glycine and imino acids, PAT1 works in cooperation with the renal sodium-hydrogen exchanger NHE3 (SLC9A3).[30] As absorption and reabsorption of glycine, proline and hydroxyproline occurs through PAT1 as well, it is believed to play another role in expressing the malabsorptive iminoglycinuria phenotype. Recent reports, however, suggest a more diminished role from PAT1 in some cases of the disorder.[4][5][30][31]
While PAT2 is strongly indicated as the primary mutagen responsible for iminoglycinuria, the variability of the phenotype is found to be instituted by three modifying genetic mutations. The major one among these is believed to be system IMINO.[4]
Defined as the sodium-dependent proline transporter not inhibited by alanine, system IMINO, believed to be formed by the SLC6A20 (SIT1) gene, is a crucial mammalian transport mechanism responsible for both renal reabsorption and intestinal absorption of proline and other imino acids, such as hydroxyproline and pipecolate.[26][27] The mRNA sequence for SIT1 is expressed in a great deal of the gastrointestinal tract, including the stomach, duodenum, jejunum, ileum, cecum and colon. It is also found in the kidney, optical choroid, and parts of the central nervous system such the brain and microglial cells.[26]
Reduced penetrance is a phenomenon where a fully inherited genetic trait, such as a disease or disorder, fails to exhibit the expected phenotype. This has been reported in some cases of iminoglycinuria.[4] Here, system IMINO is thought to play a role in reduced penetrance of iminoglycinuria by compensating for imino acid malabsorption related specifically to mutations of PAT2.[4] Conversely, SIT1 mutations are believed to result in full expression of iminoglycinuria in some cases where heterozygous mutations of PAT2 would otherwise have only been sufficient to cause hyperglycinuria.[4]
Two other transport systems are believed to play subsequent roles in iminoglycinuria, when mutations in them are present. The neutral amino acid transporter SLC6A19 (affecting glycine, proline, and other neutral amino acids like cysteine and tryptophan), associated with Hartnup disease, plays a role in iminoglycinuria as a modifier to PAT2 mutations and is also directly affected by the actions of SIT1.[4][32] The glycine-specific transporter, SLC6A18, also has an effect on the iminoglycinuria phenotype by either compounding or compensating for failures of glycine transport.[4]
To summarize, iminoglycinuria is primarily expressed by homozygous mutations of the PAT2 renal transporter, while the overall iminoglycinuria phenotype may be modified by normal or defective activity of SIT1 (IMINO), SLC6A19 and SLC6A18.[4]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (July 2017)
## Treament[edit]
This section is empty. You can help by adding to it. (July 2017)
## See also[edit]
* Pipecolic acid
* Facilitated diffusion
* Oral rehydration therapy
## References[edit]
1. ^ Ohura T (1998). "Familial iminoglycinuria". Ryoikibetsu Shokogun Shirizu (19 Pt 2): 569–571. PMID 9645136.
2. ^ a b Statter M, Ben-Zvi A, Shina A, Schein R, Russell A (Aug 1976). "Familial iminoglycinuria with normal intestinal absorption of glycine and imino acids in association with profound mental retardation, a possible "cerebral phenotype"". Helvetica Paediatrica Acta. 31 (2): 173–182. ISSN 0018-022X. PMID 955941.
3. ^ a b c Rosenberg LE, Durant JL, Elsas LJ (Jun 1968). "Familial iminoglycinuria. An inborn error of renal tubular transport". The New England Journal of Medicine. 278 (26): 1407–1413. doi:10.1056/NEJM196806272782601. ISSN 0028-4793. PMID 5652624.
4. ^ a b c d e f g h i j k l m n o p q r s t u v Bröer S, Bailey CG, Kowalczuk S, Ng C, Vanslambrouck JM, Rodgers H, Auray-Blais C, Cavanaugh, JA, Bröer A, Rasko JE (Nov 2008). "Iminoglycinuria and hyperglycinuria are discrete human phenotypes resulting from complex mutations in proline and glycine transporters" (Free full text). The Journal of Clinical Investigation. 118 (12): 3881–92. doi:10.1172/JCI36625. PMC 2579706. PMID 19033659.
5. ^ a b c d Miyauchi S, Abbot EL, Zhuang L, Subramanian R, Ganapathy V, Thwaites DT (Nov 2005). "Isolation and function of the amino acid transporter PAT1 (slc36a1) from rabbit and discrimination between transport via PAT1 and system IMINO in renal brush-border membrane vesicles". Molecular Membrane Biology. 22 (6): 549–559. doi:10.1080/09687860500421779. PMID 16373326. S2CID 40085087.
6. ^ a b Coşkun T, Ozalp I, Tokatli A (Apr 1993). "Iminoglycinuria: a benign type of inherited aminoaciduria". The Turkish Journal of Pediatrics. 35 (2): 121–125. ISSN 0041-4301. PMID 7504361.
7. ^ a b c Online Mendelian Inheritance in Man (OMIM): 242600
8. ^ Camargo SM, Bockenhauer D, Kleta R (Apr 2008). "Aminoacidurias: Clinical and molecular aspects". Kidney International. 73 (8): 918–925. doi:10.1038/sj.ki.5002790. ISSN 0085-2538. PMID 18200002.
9. ^ Lasley L, Scriver CR (Jan 1979). "Ontogeny of amino acid reabsorption in human kidney. Evidence from the homozygous infant with familial renal iminoglycinuria for multiple proline and glycine systems". Pediatric Research. 13 (1): 65–70. doi:10.1203/00006450-197901000-00014. ISSN 0031-3998. PMID 432003.
10. ^ Weinberger B, Hanna N, Laskin JD, Heck DE, Gardner CR, Gerecke DR, Laskin DL (Feb 2005). "Mechanisms mediating the biologic activity of synthetic proline, glycine, and hydroxyproline polypeptides in human neutrophils" (Free full text). Mediators of Inflammation. 2005 (1): 31–38. doi:10.1155/MI.2005.31. PMC 1513057. PMID 15770064.
11. ^ Proline at the US National Library of Medicine Medical Subject Headings (MeSH)
12. ^ a b Botany Online: Basic metabolism - Biosynthesis - Amino acids
http://www.biologie.uni-hamburg.de/b-online/e19/19e.htm Archived 2009-03-03 at the Wayback Machine
13. ^ Amino acids - Proline
http://www.biology.arizona.edu/biochemistry/problem_sets/aa/proline.html
14. ^ a b Procopis PG, Turner B (Sep 1971). "Iminoaciduria: a benign renal tubular defect". The Journal of Pediatrics. 79 (3): 419–422. doi:10.1016/S0022-3476(71)80150-6. ISSN 0022-3476. PMID 5567964.
15. ^ a b Online Mendelian Inheritance in Man (OMIM): 138500
16. ^ a b Tancredi F, Guazzi G, Auricchio S (Mar 1970). "Renal iminoglycinuria without intestinal malabsorption of glycine and imino acids". The Journal of Pediatrics. 76 (3): 386–392. doi:10.1016/S0022-3476(70)80477-2. ISSN 0022-3476. PMID 5308714.
17. ^ Greene ML, Lietman PS, Rosenberg LE, Seegmiller JE (Feb 1973). "Familial hyperglycinuria. New defect in renal tubular transport of glycine and imino acids". The American Journal of Medicine. 54 (2): 265–271. doi:10.1016/0002-9343(73)90232-5. ISSN 0002-9343. PMID 4685850.
18. ^ Kaser H, Cottier P, Antener I (Sep 1962). "Glucoglycinuria, a new familial syndrome". The Journal of Pediatrics. 61 (3): 386–394. doi:10.1016/S0022-3476(62)80369-2. ISSN 0022-3476. PMID 14454131.
19. ^ a b c Saito T, Hayasaka S, Yabata K, Omura K, Mizuno K, Tada K (Nov 1981). "Atypical gyrate atrophy of the choroid and retina and iminoglycinuria". The Tohoku Journal of Experimental Medicine. 135 (3): 331–332. doi:10.1620/tjem.135.331. ISSN 0040-8727. PMID 7314117.
20. ^ Weleber RG, Kennaway NG, Buist NR (Aug 1981). "Gyrate atrophy of the choroid and retina. Approaches to therapy". International Ophthalmology. 4 (1–2): 23–32. doi:10.1007/BF00139577. ISSN 0165-5701. PMID 7028650. S2CID 26071922.
21. ^ Rinaldi E, Stoppoloni GP, Savastano S, Russo S, Cotticelli L (Mar 1979). "Gyrate atrophy of choroid associated with hyperornithinaemia: report of the first case in Italy". Journal of Pediatric Ophthalmology and Strabismus. 16 (2): 133–135. ISSN 0191-3913. PMID 458520.
22. ^ Saito T, Omura K, Hayasaka S, Nakajima H, Mizuno K, Tada K (Dec 1981). "Hyperornithinemia with gyrate atrophy of the choroid and retina: a disturbance in de novo formation of proline". The Tohoku Journal of Experimental Medicine. 135 (4): 395–402. doi:10.1620/tjem.135.395. ISSN 0040-8727. PMID 7336429.
23. ^ De Vries A, Kochwa S, Lazebnik J, Frank M, Djaldetti M (Sep 1957). "Glycinuria, a hereditary disorder associated with nephrolithiasis". The American Journal of Medicine. 23 (3): 408–415. doi:10.1016/0002-9343(57)90320-0. ISSN 0002-9343. PMID 13458205.
24. ^ Oberiter V, Puretić Z, Fabecić-Sabadi V (Apr 1978). "Hyperglycinuria with nephrolithiasis". European Journal of Pediatrics. 127 (4): 279–285. doi:10.1007/BF00493544. ISSN 0340-6199. PMID 668712. S2CID 32224980.
25. ^ Scriver CR, Arthus MF, Bergeron M (Aug 1982). "Neonatal iminoglycinuria: evidence that the prolinuria originates in selective deficiency of transport activity in the proximal nephron". Pediatric Research. 16 (8): 684–687. doi:10.1203/00006450-198208000-00022. ISSN 0031-3998. PMID 7110792.
26. ^ a b c Takanaga H, Mackenzie B, Suzuki Y, Hediger MA (Mar 2005). "Identification of mammalian proline transporter SIT1 (SLC6A20) with characteristics of classical system imino". The Journal of Biological Chemistry. 280 (10): 8974–8984. doi:10.1074/jbc.M413027200. ISSN 0021-9258. PMID 15632147.
27. ^ a b c Kowalczuk S, Bröer A, Munzinger M, Tietzel N, Klingel K, Bröer S (Mar 2005). "Molecular cloning of the mouse IMINO system: an Na+- and Cl--dependent proline transporter". The Biochemical Journal. 386 (Pt 3): 417–422. doi:10.1042/BJ20050100. ISSN 0264-6021. PMC 1134859. PMID 15689184.
28. ^ Castagna M, Shayakul C, Trotti D, Sacchi VF, Harvey WR, Hediger MA (Jan 1997). "Molecular characteristics of mammalian and insect amino acid transporters: implications for amino acid homeostasis". The Journal of Experimental Biology. 200 (Pt 2): 269–286. ISSN 0022-0949. PMID 9050235.
29. ^ Anderson CM, Grenade DS, Boll M, Foltz M, Wake KA, Kennedy DJ, Munck LK, Miyauchi S, Taylor PM, Campbell FC, Munck BG, Daniel H, Ganapathy V, Thwaites DT (Nov 2004). "H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat". Gastroenterology. 127 (5): 1410–1422. doi:10.1053/j.gastro.2004.08.017. ISSN 0016-5085. PMID 15521011.
30. ^ a b c Thwaites DT, Anderson CM (Feb 2007). "Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1". Biochimica et Biophysica Acta (BBA) - Biomembranes. 1768 (2): 179–197. doi:10.1016/j.bbamem.2006.10.001. ISSN 0006-3002. PMID 17123464.
31. ^ Bröer A, Cavanaugh JA, Rasko JE, Bröer S (Jan 2006). "The molecular basis of neutral aminoacidurias". Pflügers Archiv : European Journal of Physiology. 451 (4): 511–517. doi:10.1007/s00424-005-1481-8. ISSN 0031-6768. PMID 16052352. S2CID 43517786.
32. ^ Ristic Z, Camargo SM, Romeo E, Bodoy S, Bertran J, Palacin M, Makrides V, Furrer EM, Verrey F (Apr 2006). "Neutral amino acid transport mediated by ortholog of imino acid transporter SIT1/SLC6A20 in opossum kidney cells". American Journal of Physiology. Renal Physiology. 290 (4): F880–F887. doi:10.1152/ajprenal.00319.2005. ISSN 0363-6127. PMID 16234310.
## External links[edit]
Classification
D
* ICD-10: E72.0
* ICD-9-CM: 270.8
* OMIM: 242600
* MeSH: C536285
* DiseasesDB: 6720
* SNOMED CT: 84121007
External resources
* Orphanet: 42062
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
* v
* t
* e
Genetic disorder, membrane: Solute carrier disorders
1-10
* SLC1A3
* Episodic ataxia 6
* SLC2A1
* De Vivo disease
* SLC2A5
* Fructose malabsorption
* SLC2A10
* Arterial tortuosity syndrome
* SLC3A1
* Cystinuria
* SLC4A1
* Hereditary spherocytosis 4/Hereditary elliptocytosis 4
* SLC4A11
* Congenital endothelial dystrophy type 2
* Fuchs' dystrophy 4
* SLC5A1
* Glucose-galactose malabsorption
* SLC5A2
* Renal glycosuria
* SLC5A5
* Thyroid dyshormonogenesis type 1
* SLC6A19
* Hartnup disease
* SLC7A7
* Lysinuric protein intolerance
* SLC7A9
* Cystinuria
11-20
* SLC11A1
* Crohn's disease
* SLC12A3
* Gitelman syndrome
* SLC16A1
* HHF7
* SLC16A2
* Allan–Herndon–Dudley syndrome
* SLC17A5
* Salla disease
* SLC17A8
* DFNA25
21-40
* SLC26A2
* Multiple epiphyseal dysplasia 4
* Achondrogenesis type 1B
* Recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
* SLC26A4
* Pendred syndrome
* SLC35C1
* CDOG 2C
* SLC39A4
* Acrodermatitis enteropathica
* SLC40A1
* African iron overload
see also solute carrier family
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Iminoglycinuria | c0268654 | 3,642 | wikipedia | https://en.wikipedia.org/wiki/Iminoglycinuria | 2021-01-18T19:08:17 | {"gard": ["8424"], "mesh": ["C536285"], "umls": ["C0268654"], "icd-9": ["270.8"], "icd-10": ["E72.0"], "orphanet": ["42062"], "wikidata": ["Q6004091"]} |
A number sign (#) is used with this entry because of evidence that familial atrial fibrillation-13 (ATFB13) is caused by heterozygous mutation in the SCN1B gene (600235) on chromosome 19q13.
Description
Atrial fibrillation is the most common sustained cardiac rhythm disturbance, affecting more than 2 million Americans, with an overall prevalence of 0.89%. The prevalence increases rapidly with age, to 2.3% between the ages of 40 and 60 years, and to 5.9% over the age of 65. The most dreaded complication is thromboembolic stroke (Brugada et al., 1997).
For a discussion of genetic heterogeneity of familial atrial fibrillation, see ATFB1 (608583).
Clinical Features
Watanabe et al. (2009) described 2 unrelated women with atrial fibrillation and a mutation in the SCN1B gene (see MOLECULAR GENETICS). One was a 68-year-old white woman with paroxysmal atrial fibrillation (AF) and moderate aortic stenosis. She was diagnosed at 58 years of age, and electrocardiogram (ECG) showed saddleback-type ST segment elevation in leads V1 to V3 that was present both during AF and during sinus rhythm, with beat-to-beat and day-to-day variability. Echocardiography revealed left atrial enlargement. No family members had documented AF, but her grandmother and daughter had a history of stroke. The other patient was a 57-year-old black woman with paroxysmal lone AF, which was diagnosed at 35 years of age. Her ECG was normal and did not show ST segment elevation or any conduction abnormality. Echocardiography revealed left atrial enlargement. At 54 years of age, she developed episodic paroxysmal AF with rapid ventricular response that was unresponsive to medication, and she underwent atrioventricular nodal ablation followed by dual-chamber pacemaker implantation. There was no family history of AF, although her mother had hypertension and a pacemaker. Neither patient had a history of ventricular tachyarrhythmias or syncope.
Molecular Genetics
Watanabe et al. (2009) screened the 4 genes encoding sodium channel beta subunits, SCN1B, SCN2B (601327), SCN3B (608214), and SCN4B (608256), in 480 patients with atrial fibrillation, including 118 patients with lone AF and 362 patients with AF and other cardiovascular disease. They identified 2 unrelated female patients, 1 with AF and aortic stenosis and 1 with lone AF, who had heterozygous missense mutations in the SCN1B gene, R85H (600235.0006) and D153N (600235.0007), respectively. Sequencing the SCN5A gene (600163) in the 2 women revealed no mutations, and the SCN1B variants were not found in a total of 638 controls. Another 2 patients were found to have mutations in the SCN2B gene (601327.0001 and 601327.0002; see ATFB14, 615378), but no disease-causing mutations were identified in SCN3B or SCN4B.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrial fibrillation, paroxysmal \- Left atrial enlargement on echocardiography \- Saddle-back ST-segment elevation in precordial leads (in some patients) \- Aortic stenosis (in some patients) MISCELLANEOUS \- Saddle-back ST-segment elevation shows beat-to-beat and day-to-day variability MOLECULAR BASIS \- Caused by mutation in the sodium channel, voltage-gated, type I, beta polypeptide gene (SCN1B, 600235.0006 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| ATRIAL FIBRILLATION, FAMILIAL, 13 | c3809311 | 3,643 | omim | https://www.omim.org/entry/615377 | 2019-09-22T15:52:24 | {"doid": ["0050650"], "omim": ["615377", "608583"], "orphanet": ["334"], "synonyms": []} |
Chromosome 15q duplication is a chromosome abnormality that occurs when an extra (duplicate) copy of the genetic material located on the long arm (q) of chromosome 15 is present in each cell. The severity of the condition and the associated signs and symptoms vary based on the size and location of the duplication and which genes are involved. Common features shared by many people with this duplication include developmental delay; intellectual disability; hypotonia (low muscle tone); seizures; high and/or cleft palate (roof of the mouth); scoliosis; slow growth; communication difficulties; behavioral problems; and distinctive facial features. Most cases are not inherited, although affected people can pass the duplication on to their children. Treatment is based on the signs and symptoms present in each person.
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Chromosome 15q duplication | c0795858 | 3,644 | gard | https://rarediseases.info.nih.gov/diseases/5314/chromosome-15q-duplication | 2021-01-18T18:01:24 | {"mesh": ["C538040"], "umls": ["C0795858"], "synonyms": ["Duplication 15q", "Trisomy 15q", "15q duplication", "15q trisomy", "Partial trisomy 15q"]} |
Busch fracture
Fracture of the dorsal base of the distal falange by extensor tendon avulsion (Busch fracture)
SpecialtyOrthopedic
In medicine a Busch fracture[1] is a type of fracture of the base of the distal phalanx of the fingers, produced by the removal of the bone insertion (avulsion) of the extensor tendon. Without the apropiate treatment, the finger becomes a hammer finger. It would correspond to the group B of the Albertoni classification.[2] It is very common in motorcycle riders and soccer joggers, caused by a hyperflection when the tendon is exercising the maximum tension (the closed hand tightening the clutch lever or the brake lever ).[3][4]
The Busch fracture is named after Friedrich Busch (1844-1916), who described this type of fracture in the 1860s. Busch's work was drawn on by Albert Hoffa in 1904, resulting in it sometimes being called a "Busch-Hoffa fracture".[5]
The mechanism of this injury can be described as an avulsion of the tendon fixed to the distal falange.[6][7][8]
## See also[edit]
* Holdsworth fracture
* Galeazzi fracture
## References[edit]
1. ^ Giovanni De Bastiani; Alan G. Apley; Anthony A.J. Goldberg (6 December 2012). Orthofix External Fixation in Trauma and Orthopaedics. Springer Science & Business Media. pp. 883–. ISBN 978-1-4471-0691-3.
2. ^ Almeida VA, Fernandes CH, Santos Jbgd Schwarz-Fernandes FA, Faloppa F, Albertoni WM (2018). "Evaluation of interobserver agreement in Albertoni's classification for mallet finger". Rev Bras Ortop. 53 (1): 2–9. doi:10.1016/j.rboe.2017.12.001. PMC 5771784. PMID 29367899.
3. ^ Tim B Hunter; Leonard F Peltier; Pamela J Lund (2000). "Musculoskeletal Eponyms: Who Are Those Guys?". RadioGraphics. 20 (3): 819–36. doi:10.1148/radiographics.20.3.g00ma20819. PMID 10835130.
4. ^ James Rheuben Andrews; Gary L. Harrelson; Kevin E. Wilk (1 January 2012). Physical Rehabilitation of the Injured Athlete. Elsevier Health Sciences. pp. 280–. ISBN 978-1-4377-2411-0.
5. ^ Samba Koné; Abdoulaye Bana; Stanislas André Touré (2015). "Hoffa fracture of medial unicondylar and bilateral in a man: a rare case". The Pan African Medical Journal. 20: 382. doi:10.11604/pamj.2015.20.382.6092. PMC 4499274. PMID 26185572.
6. ^ James H. Beaty; James R. Kasser (2010). Rockwood and Wilkins' Fractures in Children. Lippincott Williams & Wilkins. pp. 233–. ISBN 978-1-58255-784-7.
7. ^ M. Patrice Eiff; Robert L. Hatch; Walter L. Calmbach (1999). Tratamiento de las fracturas en atención primaria. Elsevier España. pp. 31–. ISBN 978-84-8174-431-6.
8. ^ Robert H. Fitzgerald; Herbert Kaufer; Arthur L. Malkani (2004). Ortopedia. Ed. Médica Panamericana. pp. 354–. ISBN 978-950-06-0791-9.
## External links[edit]
* worldcat-Friedrich Busch
Classification
D
* ICD-10: S52.3
* MeSH: 68011885
External resources
* AO Foundation: 22-A2.3
Wikimedia Commons has media related to Busch fractures.
* v
* t
* e
Fractures and cartilage damage
General
* Avulsion fracture
* Chalkstick fracture
* Greenstick fracture
* Open fracture
* Pathologic fracture
* Spiral fracture
Head
* Basilar skull fracture
* Blowout fracture
* Mandibular fracture
* Nasal fracture
* Le Fort fracture of skull
* Zygomaticomaxillary complex fracture
* Zygoma fracture
Spinal fracture
* Cervical fracture
* Jefferson fracture
* Hangman's fracture
* Flexion teardrop fracture
* Clay-shoveler fracture
* Burst fracture
* Compression fracture
* Chance fracture
* Holdsworth fracture
Ribs
* Rib fracture
* Sternal fracture
Shoulder fracture
* Clavicle
* Scapular
Arm fracture
Humerus fracture:
* Proximal
* Supracondylar
* Holstein–Lewis fracture
Forearm fracture:
* Ulna fracture
* Monteggia fracture
* Hume fracture
* Radius fracture/Distal radius
* Galeazzi
* Colles'
* Smith's
* Barton's
* Essex-Lopresti fracture
Hand fracture
* Scaphoid
* Rolando
* Bennett's
* Boxer's
* Busch's
Pelvic fracture
* Duverney fracture
* Pipkin fracture
Leg
Tibia fracture:
* Bumper fracture
* Segond fracture
* Gosselin fracture
* Toddler's fracture
* Pilon fracture
* Plafond fracture
* Tillaux fracture
Fibular fracture:
* Maisonneuve fracture
* Le Fort fracture of ankle
* Bosworth fracture
Combined tibia and fibula fracture:
* Trimalleolar fracture
* Bimalleolar fracture
* Pott's fracture
Crus fracture:
* Patella fracture
Femoral fracture:
* Hip fracture
Foot fracture
* Lisfranc
* Jones
* March
* Calcaneal
This article about an injury is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Busch fracture | None | 3,645 | wikipedia | https://en.wikipedia.org/wiki/Busch_fracture | 2021-01-18T18:54:30 | {"wikidata": ["Q11922682"]} |
Chan et al. (1984) studied immune response to 2 synthetic polypeptides: (Phe,G)-A--L, a branched copolymer of L-phenylalanine and L-glutamic acid coupled to D-L-alanine on a poly-L-lysine backbone and GAT, a random linear copolymer of glutamic acid, alanine and tyrosine in a ratio of 60:30:10. Among 92 unrelated subjects, 33% responded to (Phe,G)-A--L and 77% to GAT. No HLA association was found. Family studies showed that as in the IHG and ITG situation (146950, 146960), 2 complementary immune response genes are required for response to each antigen. Study of linkage with HLA demonstrated maximum lod scores of +4.50 for IPHEG and +7.57 for IGAT at theta = 0.0. In an HLA-B/D recombinant family, IPHEG mapped toward the D region. Localization of IGAT close to HLA-B was provided by an HLA-A/B recombinant. Except for the matings in which the complementary genes are in repulsion, inheritance followed a mendelian dominant mode. The data were explained by 2 alleles at each locus: IPHEG-1 and-2; IGAT-1 and-2. In these as in the studies with IHG and ITG, prior in vivo immunization was not required for response. There appear to be two regions in the human MHC: one distal and one proximal to HLA-B.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| IMMUNE RESPONSE TO SYNTHETIC POLYPEPTIDE--IRPHEGAL | c1840268 | 3,646 | omim | https://www.omim.org/entry/146810 | 2019-09-22T16:39:37 | {"omim": ["146810"]} |
## Description
Blount disease is a developmental condition characterized by disordered endochondral ossification of the medial part of the proximal tibial physis resulting in multiplanar deformities of the lower limb (review by Sabharwal, 2009).
Clinical Features
Blount (1937) described 22 cases of bowlegs in infants, with progressive deformity and radiologic findings of sloping proximal tibial epiphysis and a medial beak of the metaphysis. Blount (1937) suggested the existence of an infantile type with onset in the first year or two of life and an adolescent type developing just before puberty (see 259200).
Bathfield and Beighton (1978) noted a predilection for blacks.
Duncan et al. (1983) reviewed the literature emphasizing the higher frequency in blacks than in whites, the higher frequency of the infantile form than the adolescent form, and the higher frequency of bilateral involvement than unilateral involvement.
Inheritance
Blount disease is probably a multifactorial disorder with genetic, humoral, biomechanical, and environmental factors (Sabharwal, 2009).
Although Bathfield and Beighton (1978) found a modest familial aggregation, with bowlegs in 10 of 231 sibs and in 16 of the parents, multifactorial inheritance of the infantile form of Blount disease was espoused.
Sibert and Bray (1977) reported cases in infants in 4 generations and suggested autosomal dominant inheritance with incomplete penetrance. Duncan et al. (1983) referred briefly to a black family with affected members in 3 generations. McKusick (1986) observed a family of mixed African-European ancestry with 9 affected persons in 4 generations, with at least 1 instance of male-to-male transmission. The most severely affected, a male, was 76 inches tall.
Sevastikoglou and Eriksson (1967) observed 4 affected with the infantile form in a sibship of 6 children. Two of the affected were identical twins.
Ikegawa et al. (1990) described the disorder in identical twin boys who presented at the age of 1 year and 4 months with bilateral bowlegs. The family history was negative.
Joints \- Osteochondritis dissecans of knees Limbs \- Tibia vara \- Bowleg with progressive deformity Radiology \- Sloping proximal tibial epiphysis and medial beaked metaphysis Misc \- Infantile type or adolescent type Inheritance \- Autosomal dominant \- ? heterogeneous ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| BLOUNT DISEASE, INFANTILE | c0175756 | 3,647 | omim | https://www.omim.org/entry/188700 | 2019-09-22T16:32:32 | {"doid": ["14798"], "mesh": ["C536237"], "omim": ["188700"], "orphanet": ["2768"], "synonyms": ["Alternative titles", "OSTEOCHONDROSIS DEFORMANS TIBIAE, INFANTILE", "TIBIA VARA, INFANTILE"]} |
Substance intoxication
SpecialtyPsychiatry, narcology, addiction medicine
Substance intoxication is a transient condition of altered consciousness and behavior associated with recent use of a substance.[1] It is often maladaptive and impairing, but reversible.[2] If the symptoms are severe, the term "substance intoxication delirium" may be used.[3]
Substance intoxication may often accompany a substance use disorder (SUD); if persistent substance-related problems exist, SUD is the preferred diagnosis.[4]
Slang terms include: getting high (generic), being stoned, cooked, or blazed (usually in reference to cannabis),[5] and many more specific slang terms for particular intoxicants. Alcohol intoxication is graded in intensity from buzzed, to tipsy (all the way up to drunk, hammered, smashed, wasted, destroyed, shitfaced and a number of other terms).
## Contents
* 1 Classification
* 1.1 Contact high
* 2 See also
* 3 References
* 4 External links
## Classification[edit]
Examples (and ICD-10 code) include:
* F10.0 alcohol intoxication (drunk)
* F11.0 opioid intoxication
* F12.0 cannabinoid intoxication (high)
* F13.0 sedative and hypnotic intoxication (see benzodiazepine overdose and barbiturate overdose)
* F14.0 cocaine intoxication
* F15.0 caffeine intoxication
* F16.0 hallucinogen intoxication (See for example Lysergic acid diethylamide effects)
* F17.0 tobacco intoxication (See for example Nicotine poisoning)
### Contact high[edit]
The term contact high is sometimes used to describe intoxication without direct administration, either by second-hand smoke (as with cannabis), or by placebo in the presence of others who are intoxicated.
## See also[edit]
* "The spins", a state of dizziness and disorientation due to intoxication
* Toxicity
* Toxidrome
## References[edit]
1. ^ Michael B. First; Allan Tasman (2 October 2009). Clinical Guide to the Diagnosis and Treatment of Mental Disorders. John Wiley and Sons. pp. 146–. ISBN 978-0-470-74520-5. Retrieved 27 April 2010.
2. ^ Michael B. First; Allen Frances; Harold Alan Pincus (2004). DSM-IV-TR guidebook. American Psychiatric Pub. pp. 135–. ISBN 978-1-58562-068-5. Retrieved 27 April 2010.
3. ^ William H. Reid; Michael G. Wise (26 August 1995). DSM-IV training guide. Psychology Press. pp. 80–. ISBN 978-0-87630-768-7. Retrieved 27 April 2010.
4. ^ "Acute intoxication". World Health Organization. Retrieved 2020-01-31.
5. ^ Johnson BD, BardhiF, Sifaneck SJ, Dunlap E (2005). "Marijuana Argot As Subculture Threads". The British Journal of Criminology. 46 (1): 46–77. doi:10.1093/bjc/azi053.CS1 maint: multiple names: authors list (link)
## External links[edit]
Classification
D
* ICD-10: F10-F19 (with the fourth character .0)
* ICD-9-CM: 305
* MeSH: D011041
Look up substance intoxication in Wiktionary, the free dictionary.
* v
* t
* e
Psychoactive substance-related disorder
General
* SID
* Substance intoxication / Drug overdose
* Substance-induced psychosis
* Withdrawal:
* Craving
* Neonatal withdrawal
* Post-acute-withdrawal syndrome (PAWS)
* SUD
* Substance abuse / Substance-related disorders
* Physical dependence / Psychological dependence / Substance dependence
Combined
substance use
* SUD
* Polysubstance dependence
* SID
* Combined drug intoxication (CDI)
Alcohol
SID
Cardiovascular diseases
* Alcoholic cardiomyopathy
* Alcohol flush reaction (AFR)
Gastrointestinal diseases
* Alcoholic liver disease (ALD):
* Alcoholic hepatitis
* Auto-brewery syndrome (ABS)
Endocrine diseases
* Alcoholic ketoacidosis (AKA)
Nervous
system diseases
* Alcohol-related dementia (ARD)
* Alcohol intoxication
* Hangover
Neurological
disorders
* Alcoholic hallucinosis
* Alcoholic polyneuropathy
* Alcohol-related brain damage
* Alcohol withdrawal syndrome (AWS):
* Alcoholic hallucinosis
* Delirium tremens (DTs)
* Fetal alcohol spectrum disorder (FASD)
* Fetal alcohol syndrome (FAS)
* Korsakoff syndrome
* Positional alcohol nystagmus (PAN)
* Wernicke–Korsakoff syndrome (WKS, Korsakoff psychosis)
* Wernicke encephalopathy (WE)
Respiratory tract diseases
* Alcohol-induced respiratory reactions
* Alcoholic lung disease
SUD
* Alcoholism (alcohol use disorder (AUD))
* Binge drinking
Caffeine
* SID
* Caffeine-induced anxiety disorder
* Caffeine-induced sleep disorder
* Caffeinism
* SUD
* Caffeine dependence
Cannabis
* SID
* Cannabis arteritis
* Cannabinoid hyperemesis syndrome (CHS)
* SUD
* Amotivational syndrome
* Cannabis use disorder (CUD)
* Synthetic cannabinoid use disorder
Cocaine
* SID
* Cocaine intoxication
* Prenatal cocaine exposure (PCE)
* SUD
* Cocaine dependence
Hallucinogen
* SID
* Acute intoxication from hallucinogens (bad trip)
* Hallucinogen persisting perception disorder (HPPD)
Nicotine
* SID
* Nicotine poisoning
* Nicotine withdrawal
* SUD
* Nicotine dependence
Opioids
* SID
* Opioid overdose
* SUD
* Opioid use disorder (OUD)
Sedative /
hypnotic
* SID
* Kindling (sedative–hypnotic withdrawal)
* benzodiazepine: SID
* Benzodiazepine overdose
* Benzodiazepine withdrawal
* SUD
* Benzodiazepine use disorder (BUD)
* Benzodiazepine dependence
* barbiturate: SID
* Barbiturate overdose
* SUD
* Barbiturate dependence
Stimulants
* SID
* Stimulant psychosis
* amphetamine: SUD
* Amphetamine dependence
Volatile
solvent
* SID
* Sudden sniffing death syndrome (SSDS)
* Toluene toxicity
* SUD
* Inhalant abuse
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Substance intoxication | None | 3,648 | wikipedia | https://en.wikipedia.org/wiki/Substance_intoxication | 2021-01-18T18:57:01 | {"icd-9": ["305"], "icd-10": ["F1x.0"], "wikidata": ["Q865968"]} |
Sugarman syndrome
Sugarman syndrome has an autosomal recessive pattern of inheritance.
Sugarman syndrome is the common name of autosomal recessive oral-facial-digital syndrome type III, one of ten distinct genetic disorders that involve developmental defects to the mouth.[1]
Alternative names for this condition include: Brachydactyly of the hands and feet with duplication of the first toes, Sugarman brachydactyly and Brachydactyly with major proximal phalangeal shortening.[2]
## References[edit]
1. ^ "Oral-Facial-Digital Syndrome". National Organization for Rare Disorders. 2006. Retrieved 2007-04-02.
2. ^ Office of Rare Diseases (July 19, 2006). "Sugarman Syndrome". National Institutes of Health. Retrieved 2007-04-02.
## External links[edit]
Classification
D
* OMIM: 258850
* MeSH: C557817 C557817, C557817
* DiseasesDB: 31980
External resources
* Orphanet: 2752
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Sugarman syndrome | c0406726 | 3,649 | wikipedia | https://en.wikipedia.org/wiki/Sugarman_syndrome | 2021-01-18T18:40:36 | {"gard": ["10518"], "mesh": ["C557817"], "umls": ["C0406726"], "orphanet": ["2752"], "wikidata": ["Q7635034"]} |
A rare, genetic, human prion disease characterized by adult-onset neurodegenerative manifestations associated with a movement disorder and psychiatric/behavioral disturbances. Patients typically present personality changes, aggressiveness, manias, anxiety and/or depression in conjunction with rapidly progressive cognitive decline (presenting with dysarthria, apraxia, aphasia, and eventually leading to dementia) as well as ataxia (manifesting with gait disturbances, unsteadiness, coordination problems), Parkinsonism, myoclonus, and/or chorea. Additional features may include generalized spasticity, seizures, urine incontinence and pyramidal abnormalities.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Huntington disease-like 1 | c1864112 | 3,650 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=157941 | 2021-01-23T19:05:49 | {"mesh": ["C566398"], "omim": ["603218"], "umls": ["C1864112"], "icd-10": ["G10"], "synonyms": ["Early-onset prion disease with prominent psychiatric features", "HDL1"]} |
Halal (1986) described association of severe upper limb hypoplasia and mullerian duct anomalies. One or both were present in 2 males and 3 females in 3 generations. The limb anomalies varied from postaxial polydactyly to ectrodactyly to severe upper limb hypoplasia with split hand. In 1 woman, the mother of the proband, uterus didelphys (2 completely separate uterine cavities with 2 cervices) was demonstrated. Her mother also had 2 cervices. Another affected female had a vertical vaginal septum just behind an intact hymen that required hymenectomy. This appears to be distinct from other reported acrogenital syndromes.
Limbs \- Upper limb hypoplasia \- Postaxial polydactyly \- Ectrodactyly \- Split hand GU \- Mullerian duct anomalies \- Uterus didelphys \- Vertical vaginal septum \- Intact hymen Inheritance \- Autosomal dominant ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| HYPOMELIA WITH MULLERIAN DUCT ANOMALIES | c1840335 | 3,651 | omim | https://www.omim.org/entry/146160 | 2019-09-22T16:39:45 | {"mesh": ["C537155"], "omim": ["146160"], "orphanet": ["2491"], "synonyms": ["Alternative titles", "LIMB-UTERUS SYNDROME"]} |
DEAF1-related disorders are neurologic diseases that mainly present with intellectual disability, speech impairment and motor developmental delay. Additional features that have being described include seizures, brain malformations, behavioral problems, autism, stomach and/or intestinal problems, and skeletal problems (flat foot or hip dislocation). Some people with DEAF1-related disorders may also have some features that resemble another disease known as Smith-Magenis syndrome, such as intellectual disability, dysmorphic features, and sleep disturbances.. DEAF1-related disorders are caused by changes (known as pathogenic variants, or mutations) in the DEAF1 gene which activates or represses several other genes that are important for brain cell (neuron) development. There are two types of DEAF-1 disorders that have been described: an autosomal recessive DEAF-1 disorder (known as intellectual disability-epilepsy-extrapyramidal syndrome, or dyskinesia, seizures, and intellectual developmental disorder) and an autosomal dominant DEAF-1 disorder known as autosomal dominant intellectual disability 24. Treatment is directed at the specific symptoms present.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| DEAF1-associated disorders | c4310683 | 3,652 | gard | https://rarediseases.info.nih.gov/diseases/13474/deaf1-associated-disorders | 2021-01-18T18:00:57 | {"omim": ["617171", "602635"], "orphanet": ["468620"], "synonyms": ["DEAF1 related disorders", "DEAF1 autosomal dominant mutations (subtype)", "DEAF1-associated neurodevelopmental disorder", "DEAF1 mutations", "DEAF1 autosomal recessive mutations (subtype)"]} |
Pyruvate carboxylase deficiency is an inherited disorder that causes lactic acid and other potentially toxic compounds to accumulate in the blood. High levels of these substances can damage the body's organs and tissues, particularly in the nervous system.
Researchers have identified at least three types of pyruvate carboxylase deficiency, which are distinguished by the severity of their signs and symptoms. Type A, which has been identified mostly in people from North America, has severe symptoms that begin in infancy. Characteristic features include developmental delay and a buildup of lactic acid in the blood (lactic acidosis). Increased acidity in the blood can lead to vomiting, abdominal pain, extreme tiredness (fatigue), muscle weakness, and difficulty breathing. In some cases, episodes of lactic acidosis are triggered by an illness or periods without food (fasting). Children with pyruvate carboxylase deficiency type A typically survive only into infancy or early childhood.
Pyruvate carboxylase deficiency type B has life-threatening signs and symptoms that become apparent shortly after birth. This form of the condition has been reported mostly in Europe, particularly France. Affected infants have severe lactic acidosis, a buildup of ammonia in the blood (hyperammonemia), and liver failure. They experience neurological problems including weak muscle tone (hypotonia), abnormal movements, seizures, and coma. Infants with this form of the condition usually survive for less than 3 months after birth.
A milder form of pyruvate carboxylase deficiency, sometimes called type C, has also been described. This type is characterized by slightly increased levels of lactic acid in the blood and minimal signs and symptoms affecting the nervous system.
## Frequency
Pyruvate carboxylase deficiency is a rare condition, with an estimated incidence of 1 in 250,000 births worldwide. Type A appears to be much more common in some Algonkian Indian tribes in eastern Canada.
## Causes
Mutations in the PC gene cause pyruvate carboxylase deficiency. This gene provides instructions for making an enzyme called pyruvate carboxylase. This enzyme is active in mitochondria, which are the energy-producing centers within cells. It is involved in several important cellular functions, including the generation of glucose, a simple sugar that is the body's main energy source. Pyruvate carboxylase also plays a role in the formation of the protective sheath that surrounds certain nerve cells (myelin) and the production of brain chemicals called neurotransmitters that allow nerve cells to communicate with one another.
Mutations in the PC gene reduce the amount of pyruvate carboxylase in cells or disrupt the enzyme's activity. The missing or altered enzyme cannot carry out its essential role in generating glucose, which impairs the body's ability to make energy in mitochondria. Additionally, a loss of pyruvate carboxylase allows compounds such as lactic acid and ammonia to build up and damage organs and tissues. Researchers suggest that the loss of pyruvate carboxylase function in the nervous system, particularly the role of the enzyme in myelin formation and neurotransmitter production, also contributes to the neurologic features of pyruvate carboxylase deficiency.
### Learn more about the gene associated with Pyruvate carboxylase deficiency
* PC
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pyruvate carboxylase deficiency | c0034341 | 3,653 | medlineplus | https://medlineplus.gov/genetics/condition/pyruvate-carboxylase-deficiency/ | 2021-01-27T08:24:59 | {"gard": ["7512"], "mesh": ["D015324"], "omim": ["266150"], "synonyms": []} |
Rare congenital connective tissue disease
Winchester syndrome or Torg-Winchester syndrome
Other namesTorg-Winchester syndrome[1]
Matrix Metalloproteinase 2
Winchester syndrome is a rare congenital connective tissue disease described in 1969,[2] of which the main characteristics are short stature, marked contractures of joints, opacities in the cornea, coarse facial features, dissolution of the carpal and tarsal bones (in the hands and feet, respectively), and osteoporosis. Winchester syndrome was once considered to be related to a similar condition, multicentric osteolysis, nodulosis, and arthropathy (MONA).[3] However, it was discovered that the two are caused by mutations found in different genes; they are now thought of as two separate disorders. Appearances resemble rheumatoid arthritis. Increased uronic acid is demonstrated in cultured fibroblasts from the skin and to a lesser degree in both parents. Despite initial tests not showing increased mucopolysaccharide excretion, the disease was regarded as a mucopolysaccharidosis.[2] Winchester syndrome is thought to be inherited as an autosomal recessive trait.
## Contents
* 1 Symptoms
* 2 Mechanism
* 3 Diagnosis
* 4 Treatment
* 5 Research
* 6 See also
* 7 References
* 8 External links
## Symptoms[edit]
Symptoms of Winchester syndrome begin with the deterioration of bone within the hands and feet. This loss of bone causes pain and limited mobility. The abnormalities of the bone spread to other areas of the body, mostly the joints. This causes arthropathy: stiffening of the joints (contractures) and swollen joints. Many people develop osteopenia and osteoporosis throughout their entire body. Due to the damage to the bones, many affected individuals suffer from short stature and bone fractures.[4][5]
Many individuals experience leathery skin where the skin appears dark and thick. Excessive hair growth is known to be found in these darker areas of the skin (hypertrichosis). The eyes may develop a white or clear covering the cornea (corneal opacities) which can cause problems with vision.[3]
## Mechanism[edit]
Winchester syndrome is believed to be inherited through autosomal recessive inheritance.[6] For recessive genetic disorders, individuals inherit the mutated gene for the same trait from both parents. It believed that this disease is caused by a nonlysosomal connective-tissue disturbance. The protein inactivation mutation is found on the matrix metalloproteinase 2 gene (MMP2).[7] MM2 is responsible for bone remodeling. Bone remodeling is the process in which old bone is destroyed so that new bone can be created to replace it. This mutation causes a multicentric osteolysis and arthritis syndrome. It is hypothesized that the loss of an upstream MMP-2 protein activator MT1-MMP, results in decreased MMP-2 activity without affecting MMP2. The inactivating homoallelic mutation of MT1-MMP can be seen at the surface of fibroblasts. It was determined that fibroblasts lacking MT1-MMP lack the ability to degrade type I collagen which leads to anomalous function.[7]
## Diagnosis[edit]
In 1989, diagnostic criteria was created for the diagnosing of Winchester syndrome.[8] The typical diagnosis criteria begin with skeletal radiological test results and two of the defining symptoms, such as short stature, coarse facial features, hyperpigmentation, or excessive hair growth.[8] The typical tests that are performed are x-ray and magnetic resonance imaging. It appears that Winchester syndrome is more common in women than men.[4] Winchester syndrome is very rare. There have only been a few individuals worldwide who were reported to have this disorder.[3]
## Treatment[edit]
There is no known cure for Winchester syndrome; however, there are many therapies that can aid in the treatment of symptoms.[4] Such treatments can include medications: anti-inflammatories, muscle relaxants, and antibiotics. Many individuals will require physical therapy to promote movement and use of the limbs affected by the syndrome. Genetic counseling is typically prescribed for families to help aid in the understanding of the disease. There are a few clinical trials available to participate in. The prognosis for patients diagnosed with Winchester syndrome is positive. It has been reported that several affected individuals have lived to middle age; however, the disease is progressive and mobility will become limited towards the end of life. Eventually, the contractures will remain even with medical intervention, such as surgery.[4]
## Research[edit]
In 2005, a patient with Winchester syndrome was shown to have mutations in the matrix metalloproteinase 2 (MMP2) gene.[9] A 2006 study showed other mutations found in the MMP2 gene. This has led to the belief that there are many similar diseases within this family of mutations.[10] As of 2007, it was found that these mutations are also found in Torg and Nodulosis-arthropathy-osteolysis syndrome (NAO). This means that Torg, NAO, and Winchester syndrome are allelic disorders.[9] In 2014, a new case of Winchester syndrome was reported.[11] According to a recently published article, it was discovered that multicentric osteolysis, nodulosis, and arthropathy (MONA) and Winchester syndrome are different diseases. Mutations in MMPS and MT1-MMP result in similar but distinctly different "vanishing bone" syndromes.[6]
## See also[edit]
* Multicentric carpotarsal osteolysis syndrome
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Torg Winchester syndrome". www.orpha.net. Retrieved 27 April 2019.
2. ^ a b Winchester P, Grossman H, Lim WN, Danes BS (1969). "A new acid mucopolysaccharidosis with skeletal deformities simulating rheumatoid arthritis". Am J Roentgenol Radium Ther Nucl Med. 106 (1): 121–8. doi:10.2214/ajr.106.1.121. PMID 4238825.
3. ^ a b c Reference, Genetics Home. "Winchester syndrome". Genetics Home Reference. Retrieved 2017-12-12.
4. ^ a b c d "Winchester Syndrome - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2017-11-07.
5. ^ "Torg Winchester syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-12-12.
6. ^ a b Evans, Brad R.; Mosig, Rebecca A.; Lobl, Mollie; Martignetti, Chiara R.; Camacho, Catalina; Grum-Tokars, Valerie; Glucksman, Marc J.; Martignetti, John A. (2012-09-07). "Mutation of Membrane Type-1 Metalloproteinase, MT1-MMP, Causes the Multicentric Osteolysis and Arthritis Disease Winchester Syndrome". American Journal of Human Genetics. 91 (3): 572–576. doi:10.1016/j.ajhg.2012.07.022. ISSN 0002-9297. PMC 3512002. PMID 22922033.
7. ^ a b Reference, Genetics Home. "MMP14 gene". Genetics Home Reference. Retrieved 2017-11-07.
8. ^ a b "Winchester Syndrome Clinical Presentation: History, Physical Examination, Causes". emedicine.medscape.com. Retrieved 2017-12-12.
9. ^ a b Zankl A, Bonafé L, Calcaterra V, Di Rocco M, Superti-Furga A (2005). "Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2". Clin. Genet. 67 (3): 261–6. doi:10.1111/j.1399-0004.2004.00402.x. PMID 15691365.
10. ^ Rouzier C, Vanatka R, Bannwarth S, et al. (2006). "A novel homozygous MMP2 mutation in a family with Winchester syndrome". Clin. Genet. 69 (3): 271–6. doi:10.1111/j.1399-0004.2006.00584.x. PMID 16542393.
11. ^ Ekbote, Alka V.; Danda, Sumita; Zankl, Andreas; Mandal, Kausik; Maguire, Tina; Ungerer, Kobus (2014). "Patient with Mutation in the Matrix Metalloproteinase 2 (MMP2) Gene - A Case Report and Review of the Literature". Journal of Clinical Research in Pediatric Endocrinology. 6 (1): 40–46. doi:10.4274/Jcrpe.1166. ISSN 1308-5727. PMC 3986738. PMID 24637309.
## External links[edit]
Classification
D
* OMIM: 259600
External resources
* eMedicine: article/1116154
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Winchester syndrome | c0432289 | 3,654 | wikipedia | https://en.wikipedia.org/wiki/Winchester_syndrome | 2021-01-18T19:01:32 | {"mesh": ["C536709"], "umls": ["C0432289"], "orphanet": ["85196", "371428", "3460"], "wikidata": ["Q55999489"]} |
Pontocerebellar hypoplasia type 10 is a rare, genetic, pontocerebellar hypoplasia subtype characterized by severe psychomotor developmental delay, progressive microcephaly, progressive spasticity, seizures, and brain abnormalities consisting of mild atrophy of the cerebellum, pons and corpus callosum and cortical atrophy with delayed myelination. Patients may present dysmorphic facial features (high arched eyebrows, prominent eyes, long palpebral fissures and eyelashes, broad nasal root, and hypoplastic alae nasi) and an axonal sensorimotor neuropathy.
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*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pontocerebellar hypoplasia type 10 | c4014347 | 3,655 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=411493 | 2021-01-23T17:30:30 | {"omim": ["615803"], "icd-10": ["Q04.3"], "synonyms": ["CLP1-related pontocerebellar hypoplasia", "PCH10"]} |
Orofacial granulomatosis (OFG) is a condition characterized by granulomatous inflammation of regions of the mouth, jaw and face (maxillofacial), in the absence of a recognised systemic condition known to cause granulomas. Features include lip enlargement, swelling inside and around the mouth, oral ulcerations (sores), and inflammation of the gums (gingivitis). There may be only swelling inside the mouth or permanent disfiguring swelling of the lips and face. OFG includes granulomatous cheilitis (when it presents as a persistent or recurrent lip swelling), and Melkersson-Rosenthal syndrome (which includes CG, facial nerve palsy and fissured tongue) that can manifest with only CG. In some cases, orofacial granulomatosis is part of another disease such as Crohn's disease, sarcoidosis, and infectious diseases such as tuberculosis. The diagnosis of OFG is confirmed only by biopsy and microscopic tissue analysis identifying the noncaseating granulomas. When OFG occurs alone, without other associated diseases it is considered idiopathic. Up to 40% of the people with orofacial granulomatosis (OFG) may have positive reactions to patch allergy tests.
The exact prevalence of idiopathic OFG is not known, but it is considered a rare condition in most literature reports. Treatment is difficult and has to be individualized, but may include corticosteroids (systemic or injected inside the lesions), and other medication. Granulomatous cheilitis or OFG may improve with a cinnamon- and benzoate-free diet. Response to treatment is slow, and can take years, but most people improve. Surgery may be required for severe permanent swelling interfering with speaking or eating.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Orofacial Granulomatosis | c0399496 | 3,656 | gard | https://rarediseases.info.nih.gov/diseases/13106/orofacial-granulomatosis | 2021-01-18T17:58:34 | {"mesh": ["D051261"], "synonyms": []} |
Cyberchondria, otherwise known as compucondria, is the unfounded escalation of concerns about common symptomology based on review of search results and literature online.[1][2] Articles in popular media position cyberchondria anywhere from temporary neurotic excess to adjunct hypochondria. Cyberchondria is a growing concern among many healthcare practitioners as patients can now research any and all symptoms of a rare disease, illness or condition, and manifest a state of medical anxiety.[3][4]
## Contents
* 1 Derivation and use
* 2 Studies
* 2.1 Online search behaviors and their influences
* 2.2 Costs on healthcare systems
* 2.3 Remedies
* 3 Medical websites
* 4 Opening lines of communication
* 5 See also
* 6 References
* 7 External links
## Derivation and use[edit]
The term "cyberchondria" is a portmanteau neologism derived from the terms cyber- and hypochondria. (The term "hypochondrium" derives from Greek and literally means the region below the "cartilage" or "breast bone.")[5] Researchers at Harris Interactive clarified the etymology of cyberchondria, and state in studies and interviews that the term is not necessarily intended to be pejorative.[6]
A review in the British Medical Journal publication Journal of Neurology, Neurosurgery, and Psychiatry from 2003[7] says cyberchondria was used in 2001 in an article in the United Kingdom newspaper The Independent[8] to describe "the excessive use of internet health sites to fuel health anxiety." The BBC also used cyberchondria in April, 2001.[9] The BMJ review also cites the 1997 book from Elaine Showalter, who writes the internet is a new way to spread "pathogenic ideas" like Gulf War syndrome and myalgic encephalomyelitis.[10] Patients with cyberchondria and patients of general hypochondriasis often are convinced they have disorders "with common or ambiguous symptoms."[11][12]
## Studies[edit]
### Online search behaviors and their influences[edit]
The first systematic study of cyberchondria, reported in November 2008, was performed by Microsoft researchers Ryen White and Eric Horvitz, who conducted a large-scale study that included several phases of analysis.[11][13] White and Horvitz defined cyberchondria as the “unfounded escalation of concerns about common symptomatology, based on the review of search results and literature on the Web.” They analyzed a representative crawl of the web for co-occurrences of symptoms with diseases in web content as well as the content returned as search results from queries on symptoms and found high rates of linkage of rare, concerning diseases (e.g., brain tumor) to common symptoms (e.g., headache). They also analyzed anonymized large-scale logs of queries to all of the popular search engines and noted the commonality of escalations of queries from common complaints to queries on concerning diseases. They also found that potentially disruptive querying about disorders (arrived at via a search escalation) could continue in other sessions over days, weeks, and months, and that the queries could disrupt non-medical search activities.
White and Horvitz conducted a survey of over 500 people that confirmed the prevalence of web-induced medical anxieties. The survey noted that a significant portion of subjects considered the ranking of a list of results on a medical query as linked to the likelihood of relevant disorders. They point out the potential importance of findings drawn from the psychology of judgment in their work. In particular, they point out that previously studied "biases of judgment" play a role in cyberchondria.[14] The authors highlighted the potential biases of availability (the recency and density of exposure of someone to events raises the assessed likelihood of the events) and base-rate neglect (people often do not properly consider the low prior probability of events occurring) as influencing both search engines and then people searching the web. Confirmation bias, a tendency for people to confirm their preconceptions or hypotheses, may also contribute to cyberchondria.
In a paper published in the proceedings of the 2009 Symposium of the American Medical Informatics Association,[2] White and Horvitz present further findings from their 500-person survey on peoples’ experiences with the online investigation of medical concerns and self diagnosis. They found that overall, people report to having a low level of health anxiety, but that Web-based escalation of concerns occurs frequently for around one in five people. Two in five people report that interactions with the Web increases medical anxiety and approximately half of people report that it reduces anxiety. White and Horvitz suggest that Web content providers be cognizant of their potential to heighten medical anxiety and consider the ramifications of publishing alarming medical information, emphasize the importance of Web content in facilitating patient-physician interaction, and recommend periodic surveys and analysis with different cohorts to track changes in health-seeking experiences over time.
In a paper published in proceedings to the 2010 ACM Special Interest Group on Information Retrieval Conference,[15] the authors present research on predicting escalations in medical concerns based on the structure and content of Web pages encountered during medical search sessions. They construct and then characterize the performance of classifiers that predict whether an escalation will occur in issued queries following the visit to a page. Their findings show that features such as serious illness preceding benign explanations in page (e.g., cancer is mentioned before caffeine in pages pertaining to headaches), serious illness vs. benign explanation appears in page title or near beginning of page, page from Web forum, and page has external verification are all important predictors of subsequent escalation (or non-escalation).
### Costs on healthcare systems[edit]
A study by researchers from Imperial College London published in September 2018 concluded that the condition is leading to a health anxiety epidemic in the UK. According to the authors, one in five appointments at the UK's National Health Service (NHS) is now related to internet-induced irrational fears about one's state of health.[16] The study estimated the costs to the public healthcare system of such visits to be at £420 million per year "in outpatient appointments alone, with millions more spent on needless tests and scans".[16]
### Remedies[edit]
A paper from the Royal College of Surgeons in Ireland suggested that doctors annotate diagnoses posted online with complementary information, including statistics elaborating on incidence and prevalence. This was proposed as a potential means to alleviate online-induced health anxiety by placing the diagnosis into a wider context.[17]
## Medical websites[edit]
In 2002 the Sydney Morning Herald wrote "a visit to an Internet clinic will probably diagnose drowsiness as chronic fatigue, anal itch as bowel cancer and a headache as a tumour."[18] Many reputable medical organizations maintain websites that may include brief overviews of various conditions for individuals with a general curiosity, or more detailed information to aid the understanding of people who have been properly diagnosed.[7] Often listing diagnoses without regard to incidence, prevalence, or relevant risk factors, websites may lead users to suspect rather rare and unlikely diseases as the source of their complaints. Since many benign conditions share symptoms with more serious ailments and are listed side-by-side, users without proper medical consultation may assume the worst rather than the likely diagnosis. Web-diagnosis can cause a great deal of distress and anxiety in users who believe themselves to have incurable and serious illnesses.[11]
Patients who go against medical advice or refuse to accept a professional diagnosis while quoting questionable web sources have become more common and can be a frustrating obstacle to physicians trying to provide a professional standard of care. It is recommended that patients who are in doubt attempt to get a second opinion before turning to web-based sources, and that self diagnosis is not used as a substitute for a professional medical consultation.[citation needed]
## Opening lines of communication[edit]
Some medical practitioners are open to a patient's personal research, as this can open lines of communication between doctors and patients, and prove valuable in eliciting more complete or pertinent information from the patient about their present condition. One reason for this is the fact that the conditions is considered under-recognised by some medical professionals.[19]
Other doctors express concern about patients who self-diagnose on the basis of information obtained from the Internet when the patient demonstrates an incomplete or distorted understanding of other diagnostic possibilities and medical likelihoods. A patient who exaggerates one set of symptoms in support of their self-diagnosis while minimizing or suppressing contrary symptoms can impair rather than enhance a doctor's ability to reach a correct diagnosis.[9]
## See also[edit]
* Hypochondria
* Somatosensory amplification
* Self-diagnosis
* Medical students' disease
## References[edit]
1. ^ Ryen White; Eric Horvitz (2009). "Cyberchondria: Studies of the escalation of medical concerns in Web search". ACM Transactions on Information Systems. 27 (4): 1–37. doi:10.1145/1629096.1629101.
2. ^ a b White, R. W.; Horvitz, E (2009). Experiences with web search on medical concerns and self diagnosis (PDF). AMIA Annual Symposium Proceedings. 2009. pp. 696–700. PMC 2815378. PMID 20351943.
3. ^ Ferguson, Leila (2013-12-04). "Web research could give you a bad dose of cyberchondria". The Conversation. Retrieved 2017-07-20.
4. ^ Thomas, Elizabeth (11 June 2018). "Be wary of Dr Google". The Asian Age.
5. ^ Oxford English Dictionary #rd Ed. (2003)
6. ^ "The Future Use of the Internet in 4 Countries in Relation to Prescriptions, Physician Communication and Health Information" (PDF). Harris Interactive. 2002-06-20. Retrieved 2006-12-11.
7. ^ a b Stone, J; Sharpe, M (2003). "Internet resources for psychiatry and neuropsychiatry". Journal of Neurology, Neurosurgery, and Psychiatry. 74 (1): 10–2. doi:10.1136/jnnp.74.1.10. PMC 1738194. PMID 12486258.
8. ^ P. Vallely (April 18, 2001). "Are You a Cyberchondriac?". Independent.
9. ^ a b "'Cyberchondria' hits web users". BBC News. 2001-04-13. Retrieved 2006-12-11.
10. ^ Showalter, Elaine (1997). Hystories: hysterical epidemics and modern media. New York: Columbia University Press. ISBN 978-0-231-10459-3.
11. ^ a b c White, Ryen W.; Horvitz, Eric (2008). "Cyberchondria: Studies of the Escalation of Medical Concerns in Web Search" (Technical Report (MSR-TR-2008-178)). Microsoft Research. Retrieved 2008-11-26.[permanent dead link]
12. ^ Barsky, A. J.; Klerman, G. L. (1983). "Overview: Hypochondriasis, bodily complaints, and somatic styles". American Journal of Psychiatry. 140 (3): 273–283. doi:10.1176/ajp.140.3.273. PMID 6338747.
13. ^ "Microsoft Examines Causes of 'Cyberchondria'". The New York Times. 2008.
14. ^ Amos Tversky; Daniel Kahneman (1974). "Judgment under uncertainty: Heuristics and biases" (PDF). Science. 185 (4157): 1124–1131. Bibcode:1974Sci...185.1124T. doi:10.1126/science.185.4157.1124. JSTOR 1738360. PMID 17835457. Retrieved 2008-11-26.
15. ^ White, Ryen W.; Horvitz, Eric (2010). "Predicting escalations of medical queries based on web page structure and content" (PDF). Proc ACM SIGIR Conference on Research and Development in Information Retrieval (SIGIR 2010). p. 769. doi:10.1145/1835449.1835607. ISBN 978-1-4503-0153-4. Archived from the original (PDF) on 2012-10-05.
16. ^ a b Donnelly, Laura (2017-09-07). "'Cyberchondria' fuelling anxiety epidemic clogging up hospital clinics". The Telegraph. ISSN 0307-1235. Retrieved 2018-10-09.
17. ^ "The age of cyberchondria" (PDF). Royal College of Surgeons in Ireland Student Medical Journal. May 2012. Retrieved 9 October 2018.
18. ^ Natasha Wallace (September 7, 2002). "Doctor in the Mouse". Sydney Herald.
19. ^ Davis, Nicola (2018-10-08). "Cyberchondria and cyberhoarding: is internet fuelling new conditions?". the Guardian. Retrieved 2018-10-09.
## External links[edit]
Look up cyberchondria in Wiktionary, the free dictionary.
* Baumgartner, Susanne E.; Hartmann, Tilo (2011). "The Role of Health Anxiety in Online Health Information Search" (PDF). Cyberpsychology, Behavior, and Social Networking. 14 (10): 613–8. doi:10.1089/cyber.2010.0425. PMID 21548797.
* Muse, K; McManus, F; Leung, C; Meghreblian, B; Williams, J. M. (2012). "Cyberchondriasis: Fact or fiction? A preliminary examination of the relationship between health anxiety and searching for health information on the Internet" (PDF). Journal of Anxiety Disorders. 26 (1): 189–96. doi:10.1016/j.janxdis.2011.11.005. PMID 22137465. Archived from the original (PDF) on 2014-09-20. Retrieved 2016-07-27.
* Microsoft Examines Causes of ‘Cyberchondria’ a November 2008 article from The New York Times written by John Markoff
* Internet Makes Hypochondria Worse – WebMD – undated
* Confessions of a Cyberchondriac – 2009 article in Last Exit Magazine
* New disorder, cyberchondria, sweeps the internet — an April 2001 article from The New Zealand Herald
* What gets on the nerves of city docs? Surfing patients A November 2013 article from Bangalore Mirror written by Tapasya Mitra Mazumder
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cyberchondria | c4552535 | 3,657 | wikipedia | https://en.wikipedia.org/wiki/Cyberchondria | 2021-01-18T18:47:28 | {"wikidata": ["Q933899"]} |
A number sign (#) is used with this entry because of evidence that severe hypertelorism with midface prominence, myopia, mental retardation, and bone fragility can be caused by homozygous mutation in the IRX5 gene (606195) on chromosome 16q11.2.
Clinical Features
Hamamy et al. (2007) described 2 brothers, born to double first-cousin Jordanian Arab parents, with severe hypertelorism, upslanting palpebral fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and osteopenia with repeated fractures. Both had severe myopia, mild to moderate sensorineural hearing loss, and borderline intelligence. Their father had mild hypertelorism, and they had a phenotypically normal younger sister. Hamamy et al. (2007) concluded that this was a previously unrecognized autosomal or X-linked recessive syndrome.
Mapping
In 2 consanguineous families segregating an autosomal recessive craniofacial disorder, 1 of which was originally reported by Hamamy et al. (2007), Bonnard et al. (2012) performed identical-by-descent homozygosity mapping and identified a single 9.2-Mb candidate locus on chromosome 16q12.2-q21.
Molecular Genetics
In 5 affected individuals from 2 consanguineous families, 1 Turkish and the other a Jordanian family previously reported by Hamamy et al. (2007), with an autosomal recessive craniofacial syndrome mapping to chromosome 16q12.2-q21, Bonnard et al. (2012) screened 73 candidate genes and identified 2 homozygous missense mutations in the IRX5 gene (606195.0001 and 606195.0002) that segregated with disease in each family. They suggested that the disorder be designated 'Hamamy syndrome.'
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Brachycephaly \- Low posterior hair line \- Extra frontal hair whorl Face \- Bulging midface (in some patients) \- Smooth philtrum \- Long philtrum \- Parotid gland dysfunction (in some patients) \- Micrognathia, mild (in some patients) Ears \- Hearing loss, sensorineural \- Low-set ears \- Ear anomalies \- Preauricular skin tags (in some patients) Eyes \- Severe hypertelorism \- Laterally sparse eyebrows \- Myopia, progressive severe Nose \- Absence or dysfunction of nasolacrimal structures \- Broad nasal bridge \- Pointed nasal tip \- Anteverted nostrils Mouth \- High-arched palate \- Thin upper vermilion border \- Wide mouth Teeth \- Loss of lamina dura \- Thin or hypoplastic enamel \- Worn-out teeth (in some patients) \- Malocclusion (in some patients) \- Hypodontia (in some patients) Neck \- Pterygium colli \- Sloping shoulders CARDIOVASCULAR Heart \- Intraventricular conduction delay \- Mitral regurgitation (in some patients) \- Atrial septal defect (in some patients) \- Atrioventricular canal, total (in some patients) Vascular \- Patent ductus arteriosus, small (in some patients) CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum (in some patients) ABDOMEN Gastrointestinal \- Swallowing difficulties (in some patients) GENITOURINARY External Genitalia (Male) \- Inguinal hernia \- Cryptorchidism \- Absent gonad activity SKELETAL \- Generalized osteopenia Skull \- Craniosynostosis (in some patients) Pelvis \- Hip dysplasia Limbs \- Long bone fractures Hands \- Thumb deviation \- Ectopic finger creases \- Long fingers \- Short index finger \- Syndactyly (in some patients) \- Tapering fingers (in some patients) \- Clinodactyly of fifth finger Feet \- Long toes (in some patients) SKIN, NAILS, & HAIR Hair \- Low posterior hair line \- Extra frontal hair whorl NEUROLOGIC Central Nervous System \- Psychomotor retardation, moderate VOICE \- Unclear speech ENDOCRINE FEATURES \- Hypoparathyroidism HEMATOLOGY \- Anemia, microcytic hypochromic MOLECULAR BASIS \- Caused by mutation in the Iroquois homeobox protein-5 gene (IRX5, 606195.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| HAMAMY SYNDROME | c1970027 | 3,658 | omim | https://www.omim.org/entry/611174 | 2019-09-22T16:03:31 | {"mesh": ["C566988"], "omim": ["611174"], "orphanet": ["314555"], "synonyms": ["Alternative titles", "HYPERTELORISM, SEVERE, WITH MIDFACE PROMINENCE, MYOPIA, MENTAL RETARDATION, AND BONE FRAGILITY"]} |
Diencephalic-mesencephalic junction dysplasia is a rare, genetic, non-syndromic cerebral malformation characterized by severe intellectual disability, progressive postnatal microcephaly, axial hypotonia, spastic quadriparesis, seizures and facial dysmorphism (bushy eyebrows, hairy forehead, broad nasal root, long flat philtrum, V-shaped upper lip). Additionaly, talipes equinovarus, non-obstructive cardiomyopathy, persistent hyperplastic primary vitreous, obstructive hydrocephalus and autistic features may also be associated. On brain magnetic resonance imaging, the 'butterfly sign' is characterisitcally observed and cortical calcifications, agenesis of the corpus callosum, ventriculomegaly, brainstem dysplasia and cerebellar vermis hypoplasia have also been described.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Diencephalic-mesencephalic junction dysplasia | None | 3,659 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=319192 | 2021-01-23T18:38:34 | {"icd-10": ["Q04.8"]} |
A number sign (#) is used with this entry because of evidence that congenital generalized lipodystrophy type 3 (CGL3) is caused by homozygous mutation in the CAV1 gene (601047) on chromosome 7q31. One such family has been reported.
Heterozygous mutation in the CAV1 gene can cause familial partial lipodystrophy-7 (FPLD7; 606721).
Description
Congenital generalized lipodystrophy, also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis, and early onset of diabetes (Garg, 2004).
For a general description and a discussion of genetic heterogeneity of congenital generalized lipodystrophy, see CGL1 (608594).
Clinical Features
Kim et al. (2008) described a 20-year-old woman, born of consanguineous Brazilian parents, with congenital generalized lipodystrophy. Facial lipoatrophy was noted at 3 months, but development was otherwise normal except for recurrent pneumonia, chronic diarrhea, and poor growth. The patient had normal cognitive development. At age 8 years, she had generalized lipoatrophy with muscular hypertrophy, organomegaly, and features of severe insulin resistance, including acanthosis nigricans and hirsutism. She had severe hepatosplenomegaly and hepatic steatosis. Laboratory studies were consistent with diabetes mellitus, hypertriglyceridemia, and hypercholesterolemia. In addition, she had mild hypocalcemia, which was likely due to vitamin D resistance. At age 20, she had primary amenorrhea, acanthosis nigricans particularly on the neck and axillae, protruding abdomen, thick curly hair, and prominent peripheral veins in the limbs. Detailed magnetic resonance imaging of the proband confirmed near total absence of both subcutaneous and visceral adipose tissue, with only vestigial amounts in the dorsal subcutaneous regions. In contrast, bone marrow fat was well preserved. So-called mechanical adipose deposits were less severely affected, being reduced in scalp but preserved in the retroorbital region. In the extremities, adipose tissue was preserved in the fingers and the plantar region with some loss of signal intensity.
Inheritance
The transmission pattern of CGL3 in the family reported by Kim et al. (2008) was consistent with autosomal recessive inheritance.
Molecular Genetics
In a patient, born of consanguineous Brazilian parents, with CGL3, Kim et al. (2008) identified homozygosity for a premature termination mutation in exon 2 of the CAV1 gene (601047.0001). A sister of the proband, who carried the mutation in heterozygosity, was morbidly obese, suggesting that haploinsufficiency for CAV1 does not lead to globally impaired accumulation of adipose tissue. The proband's father had hypercholesterolemia and hypertension, with death at age 53 due to myocardial infarction; the heterozygous mother had both hypertension and type 2 diabetes diagnosed in her 40s. However, both heterozygous sibs examined at 18 and 23 years of age had normal metabolic parameters and blood pressure. That the sequence of CAV1 was normal in 3 other CGL patients without mutation in seipin (606158) or AGPAT2 (603100) suggested that alterations in another gene were responsible for the phenotype in these patients.
Animal Model
Razani et al. (2002) found that older Cav1-null mice had lower body weights and were resistant to diet-induced obesity compared to wildtype. Adipocytes from Cav1-null mice lacked caveolae membranes. Early on, a lack of Cav1 selectively affected only the female mammary gland fat pad and resulted in a nearly complete ablation of the hypodermal fat layer. With age, there was a systemic decompensation in lipid accumulation, resulting in smaller fat pads, reduced adipocyte cell diameter, and poorly differentiated/hypercellular white adipose parenchyma. Laboratory studies showed that Cav1-null mice had severely elevated triglyceride and free fatty acid levels, although insulin, glucose, and cholesterol levels were normal. The lean body phenotype and metabolic defects observed in these mice suggested a role for CAV1 in systemic lipid homeostasis in vivo.
INHERITANCE \- Autosomal recessive GROWTH Height \- Poor growth HEAD & NECK Face \- Facial lipoatrophy ABDOMEN Liver \- Hepatomegaly \- Hepatic steatosis Spleen \- Splenomegaly SKIN, NAILS, & HAIR \- Acanthosis nigricans \- Prominent peripheral veins in the limbs Hair \- Hirsutism MUSCLE, SOFT TISSUES \- Lipodystrophy, generalized \- Near total absence of subcutaneous and visceral adipose tissue \- Muscular appearance METABOLIC FEATURES \- Diabetes mellitus \- Insulin resistance ENDOCRINE FEATURES \- Primary amenorrhea \- Hyperandrogenism LABORATORY ABNORMALITIES \- Hypertriglyceridemia \- Hypercholesterolemia \- Hypocalcemia \- Vitamin D resistance MISCELLANEOUS \- Onset in infancy \- One patient born of consanguineous Brazilian parents has been reported (last curated March 2019) MOLECULAR BASIS \- Caused by mutation in the caveolin 1 gene (CAV1, 601047.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 3 | c0221032 | 3,660 | omim | https://www.omim.org/entry/612526 | 2019-09-22T16:01:18 | {"doid": ["0111137"], "mesh": ["D052497"], "omim": ["612526"], "orphanet": ["528"], "synonyms": ["Alternative titles", "BERARDINELLI-SEIP CONGENITAL LIPODYSTROPHY, TYPE 3", "LIPODYSTROPHY, BERARDINELLI-SEIP CONGENITAL, TYPE 3"]} |
Puncture wound caused by a bee's stinger
For other uses, see Bee sting (disambiguation).
Bee sting
The stinger of a black honey bee separated from the body and attached to a protective dressing
SpecialtyEmergency medicine
A bee sting is a wound caused by the stinger from a female bee (honey bee, bumblebee, sweat bee, etc.) being injected into one's flesh. The stings of most of these species can be quite painful, and are therefore keenly avoided by many people.
Bee stings differ from insect bites, and the venom or toxin of stinging insects is quite different. Therefore, the body's reaction to a bee sting may differ significantly from one species to another. In particular, bee stings are acidic, whereas wasp stings are alkaline, so the body's reaction to a bee sting may be very different from its reaction to a wasp sting.[1]
The most aggressive stinging insects are vespid wasps (including bald-faced hornets and other yellowjackets) and hornets (especially the Asian giant hornet).[2] All of these insects aggressively defend their nests.
Although for most people a bee sting is painful but otherwise relatively harmless, in people with insect sting allergy, stings may trigger a dangerous anaphylactic reaction that is potentially deadly. Additionally, honey bee stings release pheromones that prompt other nearby bees to attack.
## Contents
* 1 Honey bee stings
* 2 Venom and apitherapy
* 3 Treatment
* 4 See also
* 5 References
* 6 External links
## Honey bee stings[edit]
Microscope magnified image of a queen wasp's stinger
The left side of the image shows the ≈4 °C (7 °F) temperature increase (saturated red zone) caused by a bee sting after about 28 hours.
A honey bee that is away from the hive foraging for nectar or pollen will rarely sting, except when stepped on or roughly handled. Honey bees will actively seek out and sting when they perceive the hive to be threatened, often being alerted to this by the release of attack pheromones (below).
Although it is widely believed that a worker honey bee can sting only once, this is a partial misconception: although the stinger is in fact barbed so that it lodges in the victim's skin, tearing loose from the bee's abdomen and leading to its death in minutes, this only happens if the skin of the victim is sufficiently thick, such as a mammal's.[3] Honey bees are the only hymenoptera with a strongly barbed sting, though yellow jackets and some other wasps have small barbs.
The venom of the honeybee contains histamine, mast cell degranulating peptide, melittin, phospholipase A2, hyaluronidase and acid phosphatase. The three proteins in honeybee venom which are important allergens are phospholipase A2, hyaluronidase and acid phosphatase. In addition, the polypeptide melittin is also antigenic. Bumblebee venom appears to be chemically and antigenically related to honeybee venom.[4]
Bees with barbed stingers can often sting other insects without harming themselves. Queen honeybees and bees of many other species, including bumblebees and many solitary bees, have smoother stingers with smaller barbs, and can sting mammals repeatedly.[3]
The sting's injection of apitoxin into the victim is accompanied by the release of alarm pheromones, a process which is accelerated if the bee is fatally injured. The release of alarm pheromones near a hive may attract other bees to the location, where they will likewise exhibit defensive behaviors until there is no longer a threat, typically because the victim has either fled or been killed. (Note: A bee swarm, seen as a mass of bees flying or clumped together, is generally not hostile; it has deserted its hive and has no comb or young to defend.) These pheromones do not dissipate or wash off quickly, and if their target enters water, bees will resume their attack as soon as it leaves the water. The alarm pheromone emitted when a bee stings another animal smells like a banana.[5][6]
Drone bees, the males, are larger and do not have stingers. The female bees (worker bees and queens) are the only ones that can sting, and their stinger is a modified ovipositor. The queen bee has a barbed but smoother stinger and can, if need be, sting skin-bearing creatures multiple times, but the queen does not leave the hive under normal conditions. Her sting is not for defense of the hive; she only uses it for dispatching rival queens, ideally before they can emerge from their cells. Queen breeders who handle multiple queens and have the queen odor on their hands are sometimes stung by a queen.
The stinger consists of three parts: a stylus and two barbed slides (or lancets), one on either side of the stylus. The bee does not push the stinger in but it is drawn in by the barbed slides. The slides move alternately up and down the stylus so when the barb of one slide has caught and retracts, it pulls the stylus and the other barbed slide into the wound. When the other barb has caught, it also retracts up the stylus pulling the sting further in. This process is repeated until the sting is fully in and even continues after the sting and its mechanism is detached from the bee's abdomen. When a female honey bee stings a person, it cannot pull the barbed stinger back out, but rather leaves behind not only the stinger, but also part of its abdomen and digestive tract, plus muscles and nerves. This massive abdominal rupture kills the honey bee. Honey bees are the only bees to die after stinging.[7]
* Bee sting. The stinger is torn off and left in the skin.
* 2 minutes later
* 6 minutes later, after the stinger has been removed
* 27 minutes later
* A bee sting 1 day after
## Venom and apitherapy[edit]
The main component of bee venom responsible for pain in vertebrates is the toxin melittin; histamine and other biogenic amines may also contribute to pain and itching.[8] In one of the alternative medical uses of honey bee products, apitherapy, bee venom has been used to treat arthritis and other painful conditions.[9] All currently available evidence supporting this practice is either anecdotal, animal studies, or preliminary evidence, most of which has poor methodology.[10] Apitherapy is not currently accepted as a viable medical treatment for any condition or disease; the risk of allergic reaction and anaphylaxis outweighs any benefits. According to the American Cancer Society, there is no scientific evidence that apitherapy or bee venom therapy can treat or change the course of cancer or any other disease.[11] Clinical trials have shown that apitherapy is ineffective in treating multiple sclerosis or any other disease, and can exacerbate multiple sclerosis symptoms.[12]
## Treatment[edit]
The first step in treatment following a honey bee sting is removal of the stinger itself. The stinger should be removed as quickly as possible without regard to method: a study has shown the amount of venom delivered does not differ whether the sting is pinched or scraped off and even a delay of a few seconds leads to more venom being injected.[13] Once the stinger is removed, pain and swelling should be reduced with a cold compress.[14] A topical anesthetic containing benzocaine will kill pain quickly and menthol is an effective anti-itch treatment.[15] Itching can also be relieved by antihistamine or by a steroid cream.[16]
Many traditional remedies have been suggested for bee stings including damp pastes of tobacco, salt, baking soda, papain, toothpaste, clay, garlic, urine, onions, aspirin or even application of copper coins.[17][18] As with jellyfish stings, ammonia and ammonia-containing liquids, such as window cleaner, are often suggested as a way to immediately cleanse the skin and remove excess venom, and sweat itself (which also contains small amounts of ammonia) may provide some small relief.
Bee venom is acidic, and these interventions are often recommended to neutralize the venom; however, neutralizing a sting is unlikely to be effective as the venom is injected under the skin and deep into the tissues, where a topically applied alkali is unable to reach, so neutralization is unlikely to occur.[17] In any case, the amount of venom injected is typically very small (between 5 and 50 micrograms of fluid) and placing large amounts of alkali near the sting site is unlikely to produce a perfectly neutral pH to stop the pain.[17] Many people do claim benefit from these home remedies but it is doubtful they have any real physical effect on how much a sting hurts or continues hurting. The effect is probably related to rubbing the area or the mind perceiving benefit.[17] Furthermore, none of these interventions have been proven to be effective in scientific studies and a randomized trial of aspirin paste and topical ice packs showed that aspirin was not effective in reducing the duration of swelling or pain in bee and wasp stings, and significantly increased the duration of redness.[14] The study concluded that ice alone is a better treatment for bee and wasp stings than aspirin.[14]
The sting may be painful for a few hours. Swelling and itching may persist for a week. The area should not be scratched as it will only increase the itching and swelling.[citation needed] If swelling persists for over a week or covers an area greater than 7–10 cm (3–4 inches), medical attention should be sought. Doctors often recommend a tetanus immunization. For about 2 percent of people, a hypersensitivity can develop after being stung, creating a more severe reaction when stung again later. This sensitisation may happen after a single sting, or after a series of stings where they reacted normally. A highly allergic person may suffer anaphylactic shock from certain proteins in the venom, which can be life-threatening and requires emergency treatment.[19] People known to be highly allergic may carry around epinephrine (adrenaline) in the form of a self-injectable EpiPen for the treatment of an anaphylactic shock.
For patients who experience severe or life-threatening reactions to insect stings, allergy injections composed of increasing concentrations of naturally occurring venom may provide protections against future insect stings.[20]
## See also[edit]
* Apitoxin
* Bee venom therapy
* Characteristics of common wasps and bees
* Hornet stings
* Schmidt sting pain index
* Topical tobacco paste
## References[edit]
1. ^ Ewan, Pamela (1998). "ABC of allergies: Venom allergy". BMJ: British Medical Journal. 316 (7141): 1365–1368. doi:10.1136/bmj.316.7141.1365. PMC 1113072. PMID 9563993.
2. ^ Kosmeier, Dieter. "Vespa mandarinia Smith, 1852". www.vespa-crabro.com.
3. ^ a b How Bees Work – howstuffworks.com. Retrieved 22 January 2013.
4. ^ Rook's textbook of dermatology (Ninth ed.). p. 34.15. ISBN 9781118441190.
5. ^ "Analysis of Honeybee Aggression".
6. ^ Bortolotti, Laura; Costa, Cecilia (2014). "Chemical Communication in the Honey Bee Society". In Mucignat-Caretta, C (ed.). Neurobiology of Chemical Communication. Taylor & Francis. ISBN 978-1-4665-5341-5.
7. ^ Urban Bee Gardens Archived 2010-05-01 at the Wayback Machine Urban Bee Legends – by Jaime Pawelek
8. ^ Meier J, White J (1995). Clinical toxicology of animal venoms and poisons. CRC Press. ISBN 0-8493-4489-1.
9. ^ Phillip Terc. "Report about a Peculiar Connection Between the Bee stings and Rheumatism", 1888.
10. ^ Frick, Lisa (2005). "Apitherapy". Encyclopedia.com. HighBeam Research. Retrieved 28 September 2016.
11. ^ American Cancer Society's Guide to complementary and alternative cancer methods. Atlanta, Georgia: American Cancer Society. 2000. ISBN 978-0-944235-29-4.[page needed]
12. ^ "Bee Venom Therapy – Grassroots Medicine". Science-Based Medicine. Retrieved 28 September 2016.
13. ^ Visscher P, Vetter R, Camazine S (1996). "Removing bee stings". Lancet. 348 (9023): 301–2. doi:10.1016/S0140-6736(96)01367-0. PMID 8709689.
14. ^ a b c Balit C, Isbister G, Buckley N (2003). "Randomized controlled trial of topical aspirin in the treatment of bee and wasp stings". J. Toxicol. Clin. Toxicol. 41 (6): 801–8. doi:10.1081/CLT-120025345. PMID 14677790.
15. ^ "Bites, Stings and Venomous Things". National Agricultural Safety Database. May 2009. Retrieved 1 September 2015.
16. ^ "Insect Bites and Stings". patient.info. Retrieved 15 February 2015.
17. ^ a b c d Glaser, David. "Are wasp and bee stings alkali or acid and does neutralising their pH then give sting relief?". www.insectstings.co.uk. Retrieved 2016-01-05.
18. ^ Beverly Sparks, "Stinging and Biting Pests of People" Archived 2007-02-14 at the Wayback Machine Extension Entomologist of the University of Georgia College of Agricultural & Environmental Sciences Cooperative Extension Service.
19. ^ Thor Lehnert, "Hymenopterous Insect Stings" Beekeeping in the United States – USDA – Agricultural HandBook Number 335
20. ^ Resiman, R (August 1994). "Insect Stings". New England Journal of Medicine. 331 (8): 523–7. doi:10.1056/NEJM199408253310808. PMID 8041420.
## External links[edit]
* The Biology of the Honey bee, Apis Mellifera accessed August 2014
Classification
D
* ICD-10: T63.4, X23
* ICD-9-CM: 989.5, E905.3
* MeSH: D007299
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*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Bee sting | c0413120 | 3,661 | wikipedia | https://en.wikipedia.org/wiki/Bee_sting | 2021-01-18T18:52:47 | {"icd-9": ["989.5"], "icd-10": ["T63.4"], "wikidata": ["Q3523834"]} |
## Clinical Features
Dauwerse et al. (2007) described a 35-year-old male of Indonesian descent who presented with short stature and infertility due to azoospermia. Facial features were reminiscent of acrodysostosis (101800) and included a flat face with upward slanting palpebral fissures, depressed nasal bridge, broad nasal root, mildly anteverted nostrils, and low-set ears. He had extreme brachydactyly of both hands and to a lesser degree of both feet, and had partial cutaneous syndactyly between the second and third fingers on his right hand. Radiographic examination revealed severe shortening of all tubular bones in both hands, and absence of middle phalanges on the right except for a roundly ossified middle phalanx of the index finger. Both wrists showed hypoplasia of the distal ulna (ulna minor). The feet were short with broad metatarsals and phalanges and there was absence of the middle phalanx of both fifth toes due to distal symphalangism. Spine films showed a lack of interpedicular widening of the lumbar vertebrae, mild scoliosis, indentation of the vertebral endplates, and mild posterior scalloping of the lumbar vertebral bodies. He also had aortic sclerosis and insufficiency.
Cytogenetics
By chromosome analysis in a man with this apparently novel brachydactyly-syndactyly syndrome, Dauwerse et al. (2007) identified a de novo translocation t(4;6)(q12;p23). They found that the MBOAT1 gene (611732) was disrupted by the breakpoint on chromosome 6 and that no genes were disrupted on chromosome 4.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| DAUWERSE-PETERS SYNDROME | c2673203 | 3,662 | omim | https://www.omim.org/entry/611733 | 2019-09-22T16:02:54 | {"mesh": ["C567093"], "omim": ["611733"], "synonyms": ["Alternative titles", "SHORT STATURE, FACIAL DYSMORPHISM, SEVERE BRACHYDACTYLY, AND SYNDACTYLY"]} |
A number sign (#) is used with this entry because of evidence that leukoencephalopathy, brain calcifications, and cysts (LCC) is caused by homozygous or compound heterozygous mutations in the SNORD118 gene (616663) on chromosome 17p13.
Description
Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome, is characterized by a constellation of features restricted to the central nervous system, including leukoencephalopathy, brain calcifications, and cysts, resulting in spasticity, dystonia, seizures, and cognitive decline (summary by Labrune et al., 1996).
See also cerebroretinal microangiopathy with calcifications and cysts (CRMCC; 612199), an autosomal recessive disorder caused by mutation in the CTC1 gene (613129) that shows phenotypic similarities to Labrune syndrome. CRMCC includes the neurologic findings of intracranial calcifications, leukodystrophy, and brain cysts, but also includes retinal vascular abnormalities and other systemic manifestations, such as osteopenia with poor bone healing, a high risk of gastrointestinal bleeding, hair, skin, and nail changes, and anemia and thrombocytopenia. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012).
Clinical Features
Labrune et al. (1996) reported 3 unrelated children with progressive calcifications in the cerebrum and cerebellum and leukodystrophy on MRI. The changes were noted between early infancy and adolescence. Clinical features included slowing of cognition, seizures, and a movement disorder with pyramidal, extrapyramidal, and cerebellar features. Two patients became wheelchair-bound. All developed parenchymal cysts in the cerebellum or supratentorial regions. Brain biopsy of 1 patient showed angiomatous changes consisting of numerous small tortuous blood vessels with calcifications, irregular Rosenthal fibers, and hyaline deposits. Retinal abnormalities were not reported. Labrune et al. (1996) postulated a diffuse cerebral microangiopathy resulting in microcystic and macrocystic parenchymal degeneration.
Jenkinson et al. (2016) reported 40 patients from 33 unrelated families, mostly of European origin, with LCC. The patients had been collected over a period of 12 years. The age at presentation ranged between infancy and 54 years, although the vast majority of patients presented with neurologic features in the first months or years of life. Features were highly variable and included developmental delay, progressive motor disturbances, impaired gait, seizures, spasticity, dystonia, ataxia, dysarthria, and hemiparesis. Some individuals were severely impaired with mental retardation, loss of speech, and inability to walk, whereas a few patients had onset of mild motor symptoms in adulthood. Brain imaging characteristically showed white matter abnormalities in the periventricular, deep, and subcortical white matter, cysts in the deep matter, and calcifications. Brain biopsy of 1 adult patient showed numerous abnormal blood vessels resembling angioma, evidence of old hemorrhage, vascular and parenchymal calcification, and extensive gliosis with Rosenthal fibers.
Molecular Genetics
In 40 patients from 33 unrelated families with LCC, Jenkinson et al. (2016) identified biallelic mutations in the SNORD118 gene (see, e.g., 616663.0001-616663.0006). Mutations in the first families were found by a combination of linkage and haplotype analysis and exome sequencing; mutations in subsequent families were found by direct sequencing of the SNORD118 gene. All mutations were confirmed by Sanger sequencing and segregated with the disorder in the families where DNA was available. A total of 36 rare putative pathogenic variants were found, including 13 that were not present in the ExAC database or in an in-house database of over 5,000 exomes. Screening a panel of 677 European controls found that 4 individuals carried 2 rare SNORD118 variants on distinct alleles (4 of 677 compared to 20 of 20 LCC probands; p less than 0.000005). In vitro functional studies of several selected variants showed that they either impaired transcription, reduced binding to the SNU13 (601304) gene, or interfered with processing of the SNORD118 precursor RNA, consistent with a loss-of-function effect. Patient fibroblasts showed decreased SNORD118 expression and had poor growth and proliferation compared to wildtype, although there was no evidence for increased apoptosis or disturbance in the cell cycle. Additional studies showed no evidence for telomere dysfunction or disruption of TMEM107 (616183). Jenkinson et al. (2016) concluded that most patients were compound heterozygous for 1 severe and 1 mild mutation, and noted that the presence of mild recurrent variants in the general population suggested that these alleles are hypomorphic. For example, the ExAC database contained a small number of homozygotes for 5 of the 36 putative causal mutations identified. The hypomorphic variants likely contribute to the extensive phenotypic variability observed in this disorder. Jenkinson et al. (2016) also commented that since SNOR118 is a non-protein-coding portion of genomic DNA, it is more challenging to assess the biologic effects of mutations.
### Exclusion Studies
Anderson et al. (2012) excluded mutations in the CTC1 gene in 21 families with Labrune syndrome. Polvi et al. (2012) also excluded mutations in the CTC1 gene in 2 probands with cerebral calcifications, leukoencephalopathy, and brain cysts without systemic manifestations. These studies suggested that Labrune syndrome is not allelic to CRMCC.
INHERITANCE \- Autosomal recessive NEUROLOGIC Central Nervous System \- Developmental delay \- Seizures \- Gait abnormalities \- Spasticity \- Dystonia \- Ataxia \- Dysarthria \- Hemiplegia \- Tremor \- Cognitive decline \- Extrapyramidal signs \- Pyramidal signs \- Intracerebral cysts \- Intracranial calcifications \- Leukodystrophy MISCELLANEOUS \- Onset usually in childhood \- Later onset has been reported \- Highly variable severity \- Progressive disorder MOLECULAR BASIS \- Caused by mutation in the small nucleolar RNA, C/D box, 118 gene (SNORD118, 616663.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| LEUKOENCEPHALOPATHY, BRAIN CALCIFICATIONS, AND CYSTS | c3281200 | 3,663 | omim | https://www.omim.org/entry/614561 | 2019-09-22T15:54:52 | {"mesh": ["C000598644"], "omim": ["614561"], "synonyms": ["Alternative titles", "LABRUNE SYNDROME"]} |
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Find sources: "Prostatorrhea" – news · newspapers · books · scholar · JSTOR (April 2016) (Learn how and when to remove this template message)
This article is an orphan, as no other articles link to it. Please introduce links to this page from related articles; try the Find link tool for suggestions. (January 2021)
Prostatorrhea is the emission of prostatic secretions during straining associated with urination or defecation.
## References[edit]
This article about a disease of the genitourinary system is a stub. You can help Wikipedia by expanding it.
* v
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Prostatorrhea | c0392071 | 3,664 | wikipedia | https://en.wikipedia.org/wiki/Prostatorrhea | 2021-01-18T18:34:13 | {"umls": ["C0392071"], "wikidata": ["Q25091637"]} |
Distal monosomy 7p is a partial autosomal monosomy characterized by developmental delay and intellectual disability, digital anomalies, congenital heart and urogenital anomalies, and specific craniofacial features, commonly including craniosynostosis.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Distal monosomy 7p | None | 3,665 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96126 | 2021-01-23T18:15:29 | {"icd-10": ["Q93.5"], "synonyms": ["Distal deletion 7p", "Monosomy 7pter", "Telomeric deletion 7p"]} |
A number sign (#) is used with this entry because of evidence that Ehlers-Danlos syndrome musculocontractural type 1 (EDSMC1) is caused by homozygous or compound heterozygous mutation in the CHST14 gene (608429) on chromosome 15q14.
Description
The Ehlers-Danlos syndromes (EDS) are a group of heritable connective tissue disorders that share the common features of skin hyperextensibility, articular hypermobility, and tissue fragility (Beighton et al., 1998).
The major characteristics of the musculocontractural form of EDS include distinctive craniofacial dysmorphism, congenital contractures of thumbs and fingers, clubfeet, severe kyphoscoliosis, muscular hypotonia, hyperextensible thin skin with easy bruisability and atrophic scarring, wrinkled palms, joint hypermobility, and ocular involvement (summary by Malfait et al., 2010).
Janecke et al. (2015) reviewed the clinical findings in 34 reported EDSMC patients, 31 with CHST14 mutations and 3 with DSE (605942) mutations (see 615539), and stated that the disorder can be recognized based on the presence of distal arthrogryposis, including adducted thumbs or clenched fists and talipes equinovarus, as well as hands with atypically shallow palmar creases and tapering fingers, and neonatal muscular hypotonia. Characteristic craniofacial features include brachycephaly, large fontanel, hypertelorism, downslanting palpebral fissures, microcorneae, strabismus, prominent nasolabial folds, short philtrum, thin upper lip, small mouth, high palate, microretrognathia, and prominent and often low-set and posteriorly rotated ears. In addition, EDSMC patients show muscular hypoplasia and weakness, which has been confirmed by ultrasound and electromyography, and intellectual development appears to be normal.
### Genetic Heterogeneity of Musculocontractural Ehlers-Danlos Syndrome
Ehlers-Danlos syndrome musculocontractural type 2 (EDSMC2; 615539) is caused by mutation in the DSE gene (605942) on chromosome 6q22.
Nomenclature
The kyphoscoliotic type of Ehlers-Danlos syndrome (see 225400) was at one time separated into EDS VIA (with lysyl hydroxylase deficiency) and EDS VIB (with normal lysyl hydroxylase activity). What was designated EDS VIB is now known to represent 2 distinct entities: the brittle cornea syndrome (229200), caused by mutation in the ZNF469 gene (612078), and musculocontractural EDS-1.
Clinical Features
Steinmann et al. (1975) described 2 severely affected Pakistani sibs who had marked muscle weakness at birth as well as clubfeet and fragile skin, with delayed motor development but normal intellectual development. Examination at ages 18 and 20 years, respectively, showed mild scoliosis, muscular hypotonia, velvety and hyperelastic skin with hyperalgesia to pressure, hyperflexibility of joints, high narrow palate, and microcornea. Steinmann et al. (1975) reported markedly decreased lysyl hydroxylase activity in cultured skin fibroblasts from these patients, but subsequent analysis of cultured fibroblasts, both in the original laboratory and in 2 independent laboratories, showed normal levels of lysyl hydroxylase activity (Royce et al., 1989), suggesting EDS VIB. Electron microscopy of the reticular layer of the dermis revealed that a great proportion of collagen fibrils were not integrated into fibers and fiber bundles; consequently, fiber bundles were poorly delineated, and nonintegrated fibrils formed an irregular texture. Janecke et al. (2015) provided follow-up on these sibs. The brother, who had mitral valve prolapse with moderate insufficiency, died at age 28 years from fulminant endocarditis despite prophylaxis. The sister acquired large cutaneous and subcutaneous hematomas after minor trauma, and had a prolonged bleeding time with normal clotting factors. She experienced bilateral retinal detachments at age 45, and died at age 59 from intracerebral hemorrhage after a fall.
In male and female first cousins, each the offspring of consanguineous Turkish parents, Dundar et al. (1997) found severe psychomotor developmental delay, ocular anterior chamber abnormality, facial dysmorphism (broad, bossed forehead, late-closing fontanel, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, and downturned angle of mouth), arachnodactyly, and distal arthrogryposis with severely adducted thumbs and clubfeet. The patients were aged 18 months and 3.5 years. The authors noted that the phenotype had some similarities to the multiple pterygium syndrome, or Escobar syndrome (265000), but concluded that it is probably distinct and suggested the designation 'adducted thumb-clubfoot syndrome.'
Sonoda and Kouno (2000) reported 2 Japanese brothers with distal arthrogryposis involving phalangeal, hand, foot, and hip joints; abnormal facial appearance, including blepharophimosis, hypertelorism, and depressed nasal bridge, cleft palate, short stature, hydronephrosis, and undescended testes. Intelligence was normal. The parents were first cousins once removed and were phenotypically normal.
Janecke et al. (2001) described 2 male sibs, born to fourth-cousin Austrian parents, with dysmorphic facies including broad bossed forehead, telecanthus, downward slanting palpebral fissures, and abnormally placed ears. They also had widely patent anterior fontanel, low anterior hairline, brachycephaly, short neck, arachnodactyly, adducted thumbs, and bilateral talipes equinovarus. Mild ventricular enlargement with ventricular asymmetry was present, as was absent septum pellucidum in one case. One child had an atrial septal defect, mild coarctation of the aorta, and a horseshoe kidney. This child died shortly after birth from respiratory failure; the other child was reported to have decreased muscle tone but normal psychomotor development at 12 months of age. Janecke et al. (2001) pointed out the similarities between the patients they described and those described by Dundar et al. (1997) and Sonoda and Kouno (2000), and suggested that all these children had the same condition.
Dundar et al. (2001) described another case of this syndrome in the offspring of first-cousin Turkish parents. In addition to adducted thumbs and clubfeet, the clinical features included distal arthrogryposis and dysmorphic facies. The parents had 3 similarly affected children who died of unknown causes. The patient had bilateral nephrolithiasis, unilateral inguinal hernia, and bilateral cryptorchidism.
Kosho et al. (2005) reported 2 unrelated Japanese girls with an Ehlers-Danlos VIB-like phenotype who had additional clinical manifestations, including a characteristic facies with thick eyebrows, hypertelorism, blue sclerae, strabismus, hypoplastic columella, thin upper lip, high-arched palate, and low-set and slanted ears. Features present in childhood that faded with age included downslanting palpebral fissures, drooping lower eyelids, short nose, small mouth, and long philtrum. Both patients had cylindrical fingers; tubular stenosis of the phalanges, metacarpals, and metatarsals; abnormal palmar creases; absent or decreased physiologic curvature of the spine with tall vertebrae; congenital joint contractures including talipes equinovarus; and progressive talipes valgus. Both also had hearing impairment of high-pitched sounds, recurrent urinary tract infections with an enlarged or atonic bladder, and constipation. Kosho et al. (2005) noted similarities to the Pakistani brother and sister reported by Steinmann et al. (1975).
Dundar et al. (2009) provided follow-up clinical information on 7 patients with adducted thumbs and clubfeet from 4 families previously reported by Dundar et al. (1997), Sonoda and Kouno (2000), Janecke et al. (2001), and Dundar et al. (2001), respectively. Dundar et al. (2009) noted that the patients could be recognized by a pattern of features comprising a severely wasted build with dry and translucent skin, brachycephaly, and facial characteristics that included broad and flat forehead, hypertelorism, downslanting palpebral fissures, malar flatness, retrognathia, and prominent ears. The anterior fontanel was large at birth, with closure delayed until 2 years of age. The congenital contractures of the thumbs improved spontaneously within weeks, whereas the clubfeet required surgical correction. Marked arachnodactyly and tapering of the fingers, as well as hypermobility of the joints were present, and patients had delayed wound healing, ecchymoses, and hematoma formation. Coagulation studies in an 8-year-old boy previously reported by Janecke et al. (2001) revealed a prolonged bleeding time. Mild osteopenia was apparent in childhood. Minor degrees of cranial ventricular enlargement were present in all 5 patients examined, and bluish sclerae and intermittent exotropia were observed in 4 patients. Although the disorder was initially categorized as a new form of arthrogryposis, Dundar et al. (2009) concluded that it represented a recognizable generalized connective tissue disorder with normal cognitive development.
Kosho et al. (2010) described 6 Japanese patients, including the 2 unrelated female patients previously reported by Kosho et al. (2005) and a man previously studied by Yasui et al. (2003), who had distinct craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and progressive multisystem fragility-related manifestations, including recurrent large subcutaneous hematomas and other cardiac, respiratory, gastrointestinal, and ophthalmologic complications. Craniofacial features noted in infancy included large fontanel, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin vermilion of the upper lip, small mouth, and microretrognathia; in adolescence, patients developed a slender and asymmetric face with a protruding jaw. There was gross motor developmental delay noted in 5 of the 6 patients. Skeletal anomalies included flexion-adduction contractures of the bilateral thumbs in all patients as well as congenital contractures of the fingers, wrists, and hips, and talipes equinovarus with anomalous insertions of flexor muscles; progressive joint laxity with recurrent dislocations; slender and/or cylindrical fingers with progressive talipes valgus and cavum or planus, with diaphyseal narrowing of phalanges, metacarpals, and metatarsals; pectus deformities; and scoliosis or kyphoscoliosis with decreased physiologic curvature of thoracic spine and tall vertebrae. Cutaneous manifestations included progressive hyperextensibility, bruisability, and fragility of skin with atrophic scars, and fine palmar creases in childhood that appeared as prominent acrogeria-like wrinkles in adulthood. The patients all developed large recurrent subcutaneous hematomas in childhood, and had recurrent subcutaneous infections with fistula formation. Cardiac valve abnormalities, constipation, gastrointestinal diverticula with perforation, hemopneumothorax, strabismus, glaucoma, refractive errors, and hearing impairment were also observed. Kosho et al. (2010) noted similarities to the kyphoscoliosis type of Ehlers-Danlos syndrome (225400), but lysyl hydroxylase deficiency was not present in these probands. In addition, the vascular type of EDS (130050) was excluded because the patients had normal production of procollagen types I (see 120150) and III (see 120180); and they were also negative for mutation in the TGFBR1 (190181) and TGFBR2 (190182) genes, thus excluding the diagnosis of Loeys-Dietz syndrome (see LDS1, 609192).
Miyake et al. (2010) examined skin biopsies from 2 of the patients previously studied by Kosho et al. (2010) (patients 5 and 6). Light microscopy showed that fine collagen fibers were predominant in the reticular to papillary dermis and normally thick collagen bundles were markedly reduced. Electron microscopy revealed collagen fibrils that were dispersed in the reticular dermis, in contrast to the regularly and tightly assembled fibrils in a control; however, the patients' collagen fibrils were smooth and round, not varying in size or shape, similar to those of the control.
Malfait et al. (2010) reported 2 Turkish sisters and a girl of Indian origin from consanguineous families who were born with clubfeet and flexion contractures of the thumbs and developed kyphoscoliosis and joint laxity with dislocations; they also had blue sclerae and fragile, hyperextensible skin. Additional features included facial dysmorphism and ocular involvement, with early-onset high myopia, glaucoma, and retinal detachment in the Turkish sisters, and microcornea, bulging eyes, and myopia in the Indian girl. The older Turkish sister had umbilical and hiatal hernias, her younger sister had spontaneous rupture of the abdominal muscles and diastasis recti, and the Indian girl had duodenal obstruction due to malrotation requiring surgical correction. Malfait et al. (2010) stated that these patients closely resembled the Pakistani sibs described by Steinmann et al. (1975).
Uehara et al. (2018) reported the results of comprehensive investigations of spinal lesions in 12 patients from 11 families with EDSMC1. Mean age at the first visit was 13.4 years, with a range of 4 to 28 years. Scoliosis was seen in 8 patients (66.7%), with severe scoliosis in 1. Kyphosis at the thoracolumbar junction was seen in 5 (41.7%) patients. Three (25%) of the 5 had severe thoracolumbar kyphosis, 2 of whom underwent surgical correction, which was complicated by fistula formation in one and a successful 2-stage operation in the other. Cervical kyphosis was seen in 6 (50%) patients (50%), all but one of whom also had kyphosis at the thoracolumbar level. Atlantoaxial subluxation was seen in 2 patients (16.7%), and cervical vertebral malformations were seen in 10 (83.3%). Bone mineral density was measured in 6 patients, only 1 of whom had a bone mineral density lower than that of age- and sex-matched controls. Uehara et al. (2018) recommended regular surveillance including total spine radiology for patients with EDSMC1 and also recommended 2-stage surgery for patients with severe progressive thoracolumbar kyphosis. The authors noted that these findings support a critical role of dermatan sulfate in development and maintenance of the spine.
Mapping
Dundar et al. (2009) performed a genomewide linkage scan in 4 affected and 11 unaffected individuals from an Austrian family and 2 Turkish families with adducted thumb, clubfoot, and progressive joint laxity syndrome, previously described by Janecke et al. (2001) and Dundar et al. (1997, 2001), respectively. A multipoint lod score of 5.91 (theta = 0.0) was obtained at several SNPs within a 3.76-Mb interval bounded by rs10520118 and rs10518779 on chromosome 15q15, a region containing 73 genes.
Miyake et al. (2010) performed whole genome homozygosity mapping of 2 unrelated probands with bilateral thumb adduction, clubfeet, and progressive joint and skin laxity, and 6 unaffected relatives from 2 consanguineous Japanese families, respectively, 1 originally reported by Kosho et al. (2005) and the other previously studied by Kosho et al. (2010). Miyake et al. (2010) identified an 8.15-Mb homozygous region at chromosome 15q14-q15.3, obtaining a maximum lod score of 2.885; analysis of additional satellite markers narrowed the critical interval to a 7.3-Mb region containing 109 known genes.
Molecular Genetics
In 3 families with adducted thumbs, clubfeet, and progressive joint and skin laxity mapping to chromosome 15q15, Dundar et al. (2009) sequenced 2 candidate genes and identified homozygous mutations in the CHST14 gene in each family, including a 1-bp deletion (608429.0001) in the Turkish family originally reported by Dundar et al. (1997), a missense mutation (608429.0002) in the Austrian family originally reported by Janecke et al. (2001), and a complex mutation (608429.0003) in the Turkish family originally reported by Dundar et al. (2001). Subsequent analysis of the CHST14 gene in the Japanese family previously reported by Sonoda and Kouno (2000) revealed a homozygous mutation (Y293C; 608429.0004) in the 2 affected brothers. The mutations segregated with disease in each family and were not found in controls.
In 2 unrelated Japanese probands with bilateral thumb adduction, clubfeet, and progressive joint and skin laxity, 1 of whom was a female patient originally reported by Kosho et al. (2005) and the other a male patient previously studied by Kosho et al. (2010), Miyake et al. (2010) identified homozygosity for the same P281L mutation (608429.0005) in both patients. Genetic analysis of 4 more unrelated Japanese probands with similar features identified compound heterozygosity for P281L and another missense mutation (608429.0007) in a female patient originally reported by Kosho et al. (2005), compound heterozygosity for P281L and a nonsense mutation (608429.0006) in a male patient previously studied by Yasui et al. (2003), and compound heterozygosity for P281L and the Y293C mutation in 2 probands. The mutations were not identified in 376 Japanese control individuals. The 2 probands carried the same Y293C mutation as the Japanese brothers originally reported by Sonoda and Kouno (2000).
In 2 Turkish sisters and an Indian girl with a form of Ehlers-Danlos syndrome involving congenital flexion contractures of the thumbs, clubfeet, and progressive kyphoscoliosis and skin and joint laxity, Malfait et al. (2010) identified homozygosity for a 1-bp deletion (608429.0001) and a 20-bp duplication (608429.0008) in the CHST14 gene, respectively. Malfait et al. (2010) proposed that this CHST14-related disorder should be designated 'musculocontractural Ehlers-Danlos syndrome.'
Janecke et al. (2011) proposed the term 'dermatan sulfate-deficient adducted thumb-clubfoot syndrome' for this disorder, indicating that it represents another congenital disorder of glycosylation (see 212065).
In 2 unrelated Japanese boys with the musculocontractural type of Ehlers-Danlos syndrome, Shimizu et al. (2011) identified compound heterozygosity for 3 different missense mutations in the CHST14 gene (608429.0004, 608429.0005, and 608429.0008). The authors stated that phenotypic features in the 2 boys, aged 2 and 6 years, bore a striking resemblance to the features seen in infancy to early childhood in previously reported patients with the musculocontractural type of EDS. Shimizu et al. (2011) also provided a comprehensive review of 20 reported patients with CHST14 deficiency. They noted that the disorder satisfies all the hallmarks of EDS, including skin hyperextensibility, joint hypermobility, and tissue fragility affecting the skin, ligaments, joints, blood vessels, and internal organs, and that lifelong management of these patients should reflect the presence of generalized connective tissue fragility.
In a consanguineous Afghan family in which 2 sisters had the musculocontractural type of Ehlers-Danlos syndrome, Mendoza-Londono et al. (2012) identified a homozygous missense mutation in the CHST14 gene (R274P; 608429.0009) that segregated with disease. The authors stated that this was the first report of this phenotype in an Afghan family. Mendoza-Londono et al. (2012) suggested that the condition should be considered when clenched fists and amniochorion separation are seen prenatally, as was the case with the younger affected sister.
In 5 patients with the clinical hallmarks of EDSMC from 4 families with different ethnic origins, including 2 Asian families, 1 of Moroccan origin, and 1 from Curacao, Syx et al. (2015) sequenced the CHST14 gene and identified homozygous mutations in all affected individuals. Reviewing the features of the 26 previously reported EDSMC patients from 17 unrelated families with mutations in CHST14, the authors concluded that EDSMC1 is a clinically homogeneous, severe, and progressive disorder, characterized by a typical mix of symptoms that result from generalized connective tissue fragility and/or from disturbances in signaling pathways during development.
In 7 patients with EDSMC from 4 families, including the Pakistani sibs originally reported by Steinmann et al. (1975), Janecke et al. (2015) identified homozygosity or compound heterozygosity for mutations in the CHST14 gene (see, e.g., 608429.0002 and 608429.0010).
INHERITANCE \- Autosomal recessive GROWTH Weight \- Severely wasted build HEAD & NECK Head \- Brachycephaly \- Large fontanel with delayed closure Face \- Broad, flat forehead \- Microretrognathia in infancy \- Protruding jaw from adolescence \- Facial asymmetry from adolescence Ears \- Low-set and rotated ears \- Prominent ears \- Hearing impairment Eyes \- Eye anomalies, variable \- Blue sclerae \- Hypertelorism \- Downslanting palpebral fissures \- Strabismus \- Myopia \- Glaucoma \- Microcornea \- Retinal detachment \- Anterior chamber abnormality Nose \- Short with hypoplastic columella \- Long philtrum Mouth \- Thin upper lip \- Small mouth in infancy \- High-arched palate \- Cleft palate CARDIOVASCULAR Heart \- Valve anomalies \- Atrial septal defect Vascular \- Hematomas, recurrent large subcutaneous RESPIRATORY Lung \- Hemopneumothorax CHEST Ribs Sternum Clavicles & Scapulae \- Pectus excavatum \- Flat, thin pectus Diaphragm \- Hiatal hernia ABDOMEN External Features \- Umbilical hernia \- Diastasis recti Gastrointestinal \- Constipation \- Diverticular perforation (rare) \- Duodenal obstruction due to malrotation GENITOURINARY Internal Genitalia (Male) \- Cryptorchidism (in most patients) Kidneys \- Hydronephrosis, bilateral Bladder \- Cystitis, recurrent (in some patients) \- Enlarged bladder (in some patients) SKELETAL \- Mild osteopenia in childhood (in some patients) \- Congenital contractures, multiple \- Joint laxity, generalized \- Joint dislocations, recurrent \- Tendon abnormalities Spine \- Scoliosis Limbs \- Hypermobility of shoulders Hands \- Adducted thumbs, bilateral, in infancy \- Arachnodactyly \- Slender and/or cylindrical fingers \- Arthrogryposis, distal \- Hypermobility of small joints Feet \- Talipes equinovarus in infancy \- Talipes valgus and planus, progressive \- Hypermobility of small joints SKIN, NAILS, & HAIR Skin \- Hyperextensible skin \- Ecchymoses \- Fragile skin with atrophic scarring \- Delayed wound healing \- Hyperalgesia to pressure \- Palmar creases, fine to acrogeria-like \- Subcutaneous infections, recurrent, with fistula formation Skin Histology \- Fine collagen fibers predominant in reticular to papillary dermis \- Thin collagen bundles Electron Microscopy \- Collagen fibrils dispersed in reticular dermis \- Smooth, round collagen fibrils MUSCLE, SOFT TISSUES \- Hematomas, recurrent large subcutaneous \- Low muscle mass \- Hypotonia NEUROLOGIC Central Nervous System \- Gross motor developmental delay \- Mental retardation (in some patients) \- Mildly enlarged ventricles MOLECULAR BASIS \- Caused by mutation in the carbohydrate sulfotransferase-14 gene (CHST14, 608429.0001 ) ▲ Close
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| EHLERS-DANLOS SYNDROME, MUSCULOCONTRACTURAL TYPE, 1 | c1866294 | 3,666 | omim | https://www.omim.org/entry/601776 | 2019-09-22T16:14:21 | {"mesh": ["C000600608"], "omim": ["601776"], "orphanet": ["2953"], "synonyms": ["Dündar syndrome", "ADDUCTED THUMB, CLUBFOOT, AND PROGRESSIVE JOINT AND SKIN LAXITY SYNDROME", "DUNDAR SYNDROME", "Alternative titles", "EHLERS-DANLOS SYNDROME, TYPE VIB, FORMERLY", "EDSMC", "mcEDS", "Adducted thumb-clubfoot syndrome", "Ehlers-Danlos syndrome, Kosho type", "ADDUCTED THUMB-CLUBFOOT SYNDROME", "Distal arthrogryposis with peculiar facies and hydronephrosis", "ARTHROGRYPOSIS, DISTAL, WITH PECULIAR FACIES AND HYDRONEPHROSIS"]} |
Microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome is a rare developmental defect of the eye characterized by bilateral microcornea, posterior megalolenticonus, persistent fetal vasculature (extending from the posterior pole of the lens to the optic disc) and posterior chorioretinal coloboma.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome | None | 3,667 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=231736 | 2021-01-23T17:26:42 | {"gard": ["10938"], "icd-10": ["Q15.8"], "synonyms": ["MPPC syndrome"]} |
## Clinical Features
Descartes et al. (2009) reported a brother and sister with Stargardt macular degeneration (see STGD; 248200), mental retardation, and dysmorphic features. Facial features included flared eyebrows, upslanted palpebral fissures, prominent ear lobules, broad nasal tip, overcrowded teeth, high-arched palate, simple philtrum, broad face with full cheeks, and pointed chin with dimple. They both developed macular degeneration at 7 years of age. The brother had agenesis of the corpus callosum, and his sister had hypoplasia of the corpus callosum. Both had sensorineural hearing loss requiring hearing aids. The brother had a 47,XYY karyotype; that of the sister was normal.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Full cheeks \- Simple philtrum \- Pointed chin Ears \- Sensorineural hearing loss \- Prominent ear lobules Eyes \- Stargardt macular degeneration \- Strabismus \- Upslanting palpebral fissures \- Flared eyebrows Nose \- Broad nasal tip Mouth \- Thin upper lip \- Bow-shaped upper lip \- High-arched palate Teeth \- Overcrowded teeth SKELETAL Hands \- Fifth finger clinodactyly Feet \- Pes planus NEUROLOGIC Central Nervous System \- Delayed psychomotor development \- Mental retardation \- Poor eye contact \- Agenesis of the corpus callosum \- Hypoplasia of the corpus callosum ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| STARGARDT MACULAR DEGENERATION, ABSENT OR HYPOPLASTIC CORPUS CALLOSUM, MENTAL RETARDATION, AND DYSMORPHIC FACIAL FEATURES | c2751864 | 3,668 | omim | https://www.omim.org/entry/612948 | 2019-09-22T16:00:12 | {"mesh": ["C548086"], "omim": ["612948"]} |
## Description
Leptin (LEP; 164160) is a serum protein produced by adipocytes and is thought to play a role in the regulation of body fat. Leptin levels in humans are highly correlated with the individual's total adiposity (Maffei et al., 1995; Considine et al., 1996).
Mapping
Comuzzie et al. (1997) performed a genomewide scan and conducted multipoint linkage analysis using a general pedigree-based variance component approach to identify genes with measurable effects on quantitative variation in leptin levels in Mexican Americans. Strong evidence of linkage between serum leptin level and a microsatellite polymorphism, D2S1788, was found; lod score = 4.95. The D2S1788 marker mapped to chromosome 2p21, approximately 74 cM from the tip of the short arm. This quantitative trait locus accounted for 47% of the variation in serum leptin level, with a residual additive genetic component contributing an additional 24%. Comuzzie et al. (1997) noted that this region contains several potential candidate genes for obesity, including glucokinase regulatory protein (GCKR; 600842) and proopiomelanocortin (POMC; 176830). The region may contain an important human obesity gene. Rotimi et al. (1999) confirmed the QTL on chromosome 2 for serum leptin levels.
Hixson et al. (1999) typed additional markers in the region of the LSL locus, increasing the lod score to 7.46. Because this region of chromosome 2 contained the strong positional candidate gene POMC, Hixson et al. (1999) used polymorphisms in POMC to map the locus within the 95% confidence interval of the peak for the linkage signal for the QTL. Hixson et al. (1999) also constructed POMC haplotypes using these polymorphisms and found a significant association with normal variation in leptin levels (P of 0.001). They concluded that variation in POMC is associated with normal variation in serum leptin levels, providing further evidence that POMC may be the leptin QTL previously identified in Mexican American families.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| LEPTIN, SERUM LEVEL OF, QUANTITATIVE TRAIT LOCUS 1 | c1866431 | 3,669 | omim | https://www.omim.org/entry/601694 | 2019-09-22T16:14:25 | {"omim": ["601694"], "synonyms": ["Alternative titles", "LSL"]} |
Familial progressive hyperpigmentation is a rare, genetic, skin pigmentation anomaly disorder characterized by irregular patches of hyperpigmented skin which present at birth or in early infancy and increase in size, number and confluence with age. Affected areas of the body include the face, neck, trunk and limbs, as well as the palms, soles, oral mucosa and conjuctiva. No hypogmentation macules are observed and no systemic diseases are associated.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Familial progressive hyperpigmentation | c1840392 | 3,670 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=79146 | 2021-01-23T18:42:31 | {"mesh": ["C564163"], "omim": ["145250", "614233"], "umls": ["C1835039", "C1840392"], "icd-10": ["L81.4"], "synonyms": ["Melanosis diffusa congenita", "Melanosis universalis hereditaria", "Universal melanosis"]} |
Cyclic neutropenia
Other namesPeriodic neutropenia, cyclic leucopenia, cyclic hematopoesis
SpecialtyHematology
SymptomsFever, malaise, inflammation and infection of oral mucosa, respiratory tract, digestive tract, skin, and abdominal pain[1]
Usual onsetInfancy[1]
CausesMutation in ELANE gene[1]
Diagnostic methodBlood test, genetic testing[1]
TreatmentG-CSF[1]
MedicationFilgrastim[1]
Frequency1 in million (2018)[1]
Cyclic neutropenia (CyN) is a rare hematologic disorder and form of congenital neutropenia that tends to occur approximately every three weeks and lasting for few days at a time due to changing rates of neutrophil production by the bone marrow. It causes a temporary condition with a low absolute neutrophil count and because the neutrophils make up the majority of circulating white blood cells it makes the body in severe risk to inflammation and infection. In comparison to severe congenital neutropenia, it responds well to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count, shortens the cycle length, as well decreases the severity and frequency of infections.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 History
* 7 See also
* 8 References
* 9 External links
## Signs and symptoms[edit]
The common symptoms of neutropenia are recurrent fever, malaise, inflammation of the tissues surrounding the teeth, mouth ulcers, inflammation and bacterial infection of the respiratory tract, digestive tract, skin, and abdominal pain.[1][2] It is considered that the greatest risk for death is from developing necrotizing enterocolitis (NEC), peritonitis, bacteremia or Clostridium and Escherichia coli sepsis and septic shock, and pneumonia.[1][3][4]
## Causes[edit]
Cyclic neutropenia (CyN), like severe congenital neutropenia (SCN), is a rare disorder. It is considered that in the general population, CyN has a frequency of one in one million.[1] It is the result of autosomal dominant mutation in ELANE gene located on the short arm (p) of chromosome 19 (19p13.3), the gene encoding neutrophil elastase, which is also the most common cause of the SCN.[1][5][6][7] It sporadically occurs as a de novo mutation variant or can be present among members of the same family.[1] In the case of CyN, the mutation variants have been found to mostly cluster in intron 4 and exon 4 and 5,[6][3] but were also located in intron 3, and exon 2 and 3.[8][9][10][11][12] Some mutation variants have been found in both Cyn and SCN, which indicates they are phenotypes of the same disease with different severity.[9]
It is considered that the mutation causes a decrease in the "neutrophil production or excessive apoptosis (shorter half-life)" which results in a deficiency of mature neutrophils in the blood.[13] The exact pathological mechanism is still researched, with the main hypotheses being mislocalization of ELANE or unfolded protein response (UPR) induced by mutant ELANE,[14] however according to Mehta et al. (2016), the "UPR induction by mutant ELANE is not strong enough to promote cell death and that mutant ELANE causes SCN through an alternative mechanism".[15] According to Garg et al. (2020), new "findings challenge the currently prevailing model that SCN results from mutant ELANE, which triggers endoplasmic reticulum stress, UPR, and apoptosis".[16] The expression of the ELANE gene has been linked to GFI1 gene,[8][17] and some considered that interaction with other genes causes the emergence and severity of one or the other phenotypic disorder.[9] It is unclear what causes the cyclic aspect in CyN.[17] According to Donadieu et al. (2011), the "cyclic aspect ... suggests the existence of a cryptic biological clock that regulates granulopoiesis. This putative clock might be revealed by particular mutations".[13] Michael Mackey "postulates that the production of neutrophils is governed by long‐range stimulatory factors in a long feedback loop that has a built‐in time delay in the maturation of promyelocytes to fully differentiated neutrophils".[18] It is also not clear what causes that the levels of secretory leucocyte protease inhibitor (SLPI), which influences the induction of the unfolded protein response (UPR), are not diminished and as such activation of UPR is absent in CyN compared to SCN, in other words, different ELANE mutations "have different effects on UPR activation, and SLPI regulates the extent of ELANE‐triggered UPR".[19]
"A hypothesis of UPR‐induced cycling of hematopoiesis. Schematic of the relationship between peripheral blood ANC (purple line) and UPR intensity in bone marrow HSCs and progenitor cells of CyN patients", per Mir et al. (2020).[18]
According to 2020 study published in Annals of the New York Academy of Sciences about the pathomechanism of CyN, was revealed that "some HSPCs escape the UPR‐induced endoplasmic reticulum (ER) stress and proliferate in response to granulocyte colony‐stimulating factor (G‐CSF) to a certain threshold at which UPR again affects the majority of HSPCs. There is a cyclic balance between ER stress-induced apoptosis of HSPCs and compensatory G‐CSF–stimulated HSPC proliferation followed by granulocytic differentiation", in other words, CyN is "characterized by cycling UPR activities and cycling UPR‐escaping cells". Also, the most probable reason that from the same mutation variant develops SCN and not CyN is due to more severe damage caused by UPR stress in SCN.[18]
## Diagnosis[edit]
A diagnosis is usually confirmed by monitoring absolute neutrophil (ANC) count three times per week for at least six weeks.[1][3] The confirmation can be assisted with Lomb periodogram.[20] During the condition, which lasts for three to six days and tends to occur approximately every three weeks (but can range from 14 to 36 days),[2][3] the absolute neutrophil count (ANC) is less than 200-500 cells/microL (<0.2-0.5x109/L), with increase of monocyte counts, and mild oscillations of other cells, including a mild anemia.[1][21] Between cycles the neutrophil count mostly peaks at subnormal or normal values.[17]
It is advised genetic testing for mutations in the ELANE and other neutropenia related genes (like HAX1, G6PC3, GFI1 etc.) to differentiate it from other secondary causes and forms of neutropenia.[1][22] In some cases intervals and oscillations can be lower making the ANC analysis insufficient,[1] and since both disorders can have the same mutation variants in ELANE it is preferable to have both ANC and genetic analysis to confirm in the diagnosis whether it is severe congenital or cyclic neutropenia.[21][20]
## Treatment[edit]
"Cycling peripheral blood ANCs in CyN patients. Time course of ANC numbers in one CyN patient after initiation of G‐CSF therapy", per Mir et al. (2020).[18]
Although individuals between cycles are generally healthy and symptoms tend to improve in adulthood, it is advised avoiding activities prone to injuries, to have regular oral and dental care,[2] and BCG vaccine to be avoided.[1][13] It is advised monitoring white blood cells several times a year. The treatment following the symptoms should be immediate to prevent infections, especially during a fever when it requires broad-spectrum antibiotic therapy (see febrile neutropenia). The most important and often life-saving treatment is the preventive therapy of granulocyte colony-stimulating factor (G-CSF), in the form of filgrastim, which regulates the production of neutrophils within the bone marrow, but shortens the neutropenic cycle to about 7-14 days and the duration of the severe condition.[1][17] The subcutaneous injections, with median dosage of 1.5 μg/kg/day,[18] can be given daily, intermittently once every three days, or timed to just treat the neutropenic period.[13][23] The therapy is considered to be "safe and effective", with no significant adverse effects,[24] besides a possibility of development of osteopenia.[21]
The granulocyte-macrophage colony-stimulating factor (GM-CSF) is less effective with more adverse effects. Another alternative is hematopoietic stem cell transplantation (HSCT), but is usually practiced in SCN,[1] and in one case between two sibling donors, one of which was undergoing HSCT treatment for acute myeloid leukemia (AML) while the second had CyN and whose marrow was transferred, was also transferred CyN through allogeneic marrow grafting. It shows that CyN is a stem cell disorder.[25] Yearly bone marrow examinations are not recommended.[23]
## Prognosis[edit]
There is a very high risk of life-threatening infections and death at an early age.[13] The quality of life and survival greatly improves with G-CSF treatment, which is practiced since the late 1980s.[21] Unlike severe congenital neutropenia, individuals with cyclic neutropenia have a better response to G-CSF and do not have a risk of developing myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).[1][3] However, in long-term observation of over 300 patients with CyN, there has been one case of developing chronic myelogenous leukemia (CML) and one of AML,[21][24] indicating it is also a pre-leukemic condition, but the risk is "very low" (1%[18]),[26] and the risk is "correlated with disease severity rather than with occurrence of an ELANE mutation".[10] According to Donadieu et al. (2011), "the cumulative risk of experiencing at least one serious (potentially life-threatening) infection by age 20 years is similar in patients with permanent and cyclic neutropenia, although the former patients tend to have earlier manifestations".[13]
## History[edit]
First described in 1910,[21][2] it was suggested and confirmed to have an autosomal dominant (AD) inheritance in the 1940s and 1960s,[27] but was differentiated from congenital neutropenias until the 1990s when were analyzed pedigrees and identified genetic mutations shared by patients with severe congenital neutropenia.[13]
## See also[edit]
* Leukopenia
* Agranulocytosis
## References[edit]
1. ^ a b c d e f g h i j k l m n o p q r s t Dale DC, Makaryan V (2018) [2002]. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJ (eds.). "ELANE-Related Neutropenia". GeneReviews. PMID 20301705.
2. ^ a b c d Olvera KI, Barrios VM, Ríos RF, Ruidíaz VC (2015). "Cyclic neutropenia. Clinical case report". Revista Odontológica Mexicana. 19 (4): 246–252. doi:10.1016/j.rodmex.2015.10.015. Retrieved 2019-08-12.
3. ^ a b c d e Boxer LA (2012). "How to approach neutropenia". Hematology. American Society of Hematology. Education Program. 2012 (1): 174–82. doi:10.1182/asheducation.v2012.1.174.3798251. PMID 23233578.
4. ^ James WD, Elston DM, Berger TG, Andrews GC (2006). Andrews' Diseases of the Skin: Clinical Dermatology. Saunders Elsevier. p. 808–811. ISBN 978-0-7216-2921-6.
5. ^ Sera Y, Kawaguchi H, Nakamura K, Sato T, Habara M, Okada S, et al. (August 2005). "A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia". Haematologica. 90 (8): 1032–41. PMID 16079102.
6. ^ a b Makaryan V, Zeidler C, Bolyard AA, Skokowa J, Rodger E, Kelley ML, et al. (January 2015). "The diversity of mutations and clinical outcomes for ELANE-associated neutropenia". Current Opinion in Hematology. 22 (1): 3–11. doi:10.1182/blood.V118.21.3398.3398. PMC 4380169. PMID 25427142.
7. ^ Horwitz MS, Corey SJ, Grimes HL, Tidwell T (February 2013). "ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology". Hematology/Oncology Clinics of North America. 27 (1): 19–41, vii. doi:10.1016/j.hoc.2012.10.004. PMC 3559001. PMID 23351986.
8. ^ a b Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, et al. (June 2004). "Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register". Blood. 103 (11): 4119–25. doi:10.1182/blood-2003-10-3518. PMID 14962902.
9. ^ a b c Newburger PE, Pindyck TN, Zhu Z, Bolyard AA, Aprikyan AA, Dale DC, et al. (August 2010). "Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype: evidence for phenotype determination by modifying genes". Pediatric Blood & Cancer. 55 (2): 314–7. doi:10.1002/pbc.22537. PMC 2913300. PMID 20582973.
10. ^ a b Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz CP, Ballmaier M (June 2013). "The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia". Human Mutation. 34 (6): 905–14. doi:10.1002/humu.22308. PMID 23463630.
11. ^ Makaryan V, Zeidler C, Bolyard AA, Skokowa J, Rodger E, Kelley ML, et al. (January 2015). "The diversity of mutations and clinical outcomes for ELANE-associated neutropenia". Current Opinion in Hematology. 22 (1): 3–11. doi:10.1097/MOH.0000000000000105. PMC 4380169. PMID 25427142.
12. ^ Liu Y, Fu J, Zhang J, Wang Y, Guan X (2017). "A Case Report on Recurrent Oral Ulcers Associated with Cyclic Neutropenia". Annals of Clinical Case Reports. 2: 905–914. ISSN 2474-1655. S2CID 21701463.
13. ^ a b c d e f g Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB (May 2011). "Congenital neutropenia: diagnosis, molecular bases and patient management". Orphanet Journal of Rare Diseases. 6: 26. doi:10.1186/1750-1172-6-26. PMC 3127744. PMID 21595885.
14. ^ Horwitz MS, Laurino MY, Keel SB (August 2019). "ELANE whole gene deletion mutation". Blood Advances. 3 (16): 2470–2473. doi:10.1182/bloodadvances.2019000498. PMC 6712528. PMID 31427279.
15. ^ Mehta HM, Das A, Kamel R, Horwitz M, Corey S (December 2016). "Conditional Expression of Mutant ELANE Produces Unfolded Protein Response but Fails to Promote Cell Death or Differentiation Block: What Is the Mechanism for Severe Congenital Neutropenia?". Blood. 128 (22): 3899. doi:10.1182/blood.V128.22.3899.3899.
16. ^ Garg B, Mehta HM, Wang B, Kamel R, Horwitz MS, Corey SJ (May 2020). "ELANE mutation impairs granulocytic differentiation, without eliciting an unfolded protein response". The Journal of Biological Chemistry. 295 (21): 7492–7500. doi:10.1074/jbc.RA120.012366. PMC 7247317. PMID 32299910.
17. ^ a b c d Horwitz MS, Duan Z, Korkmaz B, Lee HH, Mealiffe ME, Salipante SJ (March 2007). "Neutrophil elastase in cyclic and severe congenital neutropenia". Blood. 109 (5): 1817–24. doi:10.1182/blood-2006-08-019166. PMC 1801070. PMID 17053055.
18. ^ a b c d e f Mir P, Klimiankou M, Findik B, Hähnel K, Mellor-Heineke S, Zeidler C, et al. (April 2020). "New insights into the pathomechanism of cyclic neutropenia". Annals of the New York Academy of Sciences. 1466 (1): 83–92. Bibcode:2020NYASA1466...83M. doi:10.1111/nyas.14309. PMID 32083314.
19. ^ Nustede R, Klimiankou M, Klimenkova O, Kuznetsova I, Zeidler C, Welte K, Skokowa J (January 2016). "ELANE mutant-specific activation of different UPR pathways in congenital neutropenia". British Journal of Haematology. 172 (2): 219–27. doi:10.1111/bjh.13823. PMID 26567890.
20. ^ a b Dale DC, Bolyard AA, Leung J, Tran E, Marrero TM, Newburger PE (2017). "Cyclic Neutropenia, Congenital and Idiopathic Neutropenia". Blood. 130: 2275. Retrieved 2019-08-12.
21. ^ a b c d e f Dale DC, Bolyard AA, Marrero TM, Bonilla MA, Link DC, Newburger PE, Shimamura A, Boxer LA (2012). "The Natural History of Cyclic Neutropenia: Long-Term Prospective Observations and Current Perspectives". Blood. 120 (21): 2141. doi:10.1182/blood.V120.21.2141.2141. Retrieved 2019-08-12.
22. ^ Arun AK, Senthamizhselvi A, Hemamalini S, Edison ES, Korula A, Fouzia NA, et al. (December 2018). "ELANE mutations in congenital neutropenia: a single-centre study in patients of Indian origin". Journal of Clinical Pathology. 71 (12): 1046–1050. doi:10.1136/jclinpath-2018-205235. PMID 30171085. S2CID 52141047.
23. ^ a b Dale DC (August 2017). "How I manage children with neutropenia". British Journal of Haematology. 178 (3): 351–363. doi:10.1111/bjh.14677. PMID 28419427.
24. ^ a b Dale DC, Bolyard A, Marrero T, Makaryan V, Bonilla M, Link DC, et al. (December 2017). "Long-Term Effects of G-CSF Therapy in Cyclic Neutropenia". The New England Journal of Medicine. 377 (23): 2290–2292. doi:10.1056/NEJMc1709258. PMC 5777346. PMID 29211670.
25. ^ Krance RA, Spruce WE, Forman SJ, Rosen RB, Hecht T, Hammond WP, Blume KG (December 1982). "Human cyclic neutropenia transferred by allogeneic bone marrow grafting". Blood. 60 (6): 1263–6. doi:10.1182/blood.V60.6.1263.1263. PMID 6753968.
26. ^ Zeidler C, Mellor-Heineke S, Klimiankou M, Skokowa J, Welte K (2015). "First Case of Leukemia in a Child Suffering from Cyclic Neutropenia with ELANE Mutation". Blood. 126 (23): 997. doi:10.1182/blood.V126.23.997.997.
27. ^ Patil VH, Hugar SM, Balikai G, Patil S (2016). "Severe congenital cyclic neutropenia: A case report". International Journal of Applied & Basic Medical Research. 6 (4): 293–296. doi:10.4103/2229-516X.192598. PMC 5108111. PMID 27857902.
## External links[edit]
* Severe Chronic Neutropenia International Registry
* "Understanding Neutropenia: The 20 Year Experience of the Severe Chronic Neutropenia International Registry (SCNIR)" (2014)
Classification
D
* ICD-9-CM: 288.02
* OMIM: 162800
* MeSH: C536227
* DiseasesDB: 30103
External resources
* GeneReviews: ELANE-Related Neutropenia
* v
* t
* e
Oral and maxillofacial pathology
Lips
* Cheilitis
* Actinic
* Angular
* Plasma cell
* Cleft lip
* Congenital lip pit
* Eclabium
* Herpes labialis
* Macrocheilia
* Microcheilia
* Nasolabial cyst
* Sun poisoning
* Trumpeter's wart
Tongue
* Ankyloglossia
* Black hairy tongue
* Caviar tongue
* Crenated tongue
* Cunnilingus tongue
* Fissured tongue
* Foliate papillitis
* Glossitis
* Geographic tongue
* Median rhomboid glossitis
* Transient lingual papillitis
* Glossoptosis
* Hypoglossia
* Lingual thyroid
* Macroglossia
* Microglossia
* Rhabdomyoma
Palate
* Bednar's aphthae
* Cleft palate
* High-arched palate
* Palatal cysts of the newborn
* Inflammatory papillary hyperplasia
* Stomatitis nicotina
* Torus palatinus
Oral mucosa – Lining of mouth
* Amalgam tattoo
* Angina bullosa haemorrhagica
* Behçet's disease
* Bohn's nodules
* Burning mouth syndrome
* Candidiasis
* Condyloma acuminatum
* Darier's disease
* Epulis fissuratum
* Erythema multiforme
* Erythroplakia
* Fibroma
* Giant-cell
* Focal epithelial hyperplasia
* Fordyce spots
* Hairy leukoplakia
* Hand, foot and mouth disease
* Hereditary benign intraepithelial dyskeratosis
* Herpangina
* Herpes zoster
* Intraoral dental sinus
* Leukoedema
* Leukoplakia
* Lichen planus
* Linea alba
* Lupus erythematosus
* Melanocytic nevus
* Melanocytic oral lesion
* Molluscum contagiosum
* Morsicatio buccarum
* Oral cancer
* Benign: Squamous cell papilloma
* Keratoacanthoma
* Malignant: Adenosquamous carcinoma
* Basaloid squamous carcinoma
* Mucosal melanoma
* Spindle cell carcinoma
* Squamous cell carcinoma
* Verrucous carcinoma
* Oral florid papillomatosis
* Oral melanosis
* Smoker's melanosis
* Pemphigoid
* Benign mucous membrane
* Pemphigus
* Plasmoacanthoma
* Stomatitis
* Aphthous
* Denture-related
* Herpetic
* Smokeless tobacco keratosis
* Submucous fibrosis
* Ulceration
* Riga–Fede disease
* Verruca vulgaris
* Verruciform xanthoma
* White sponge nevus
Teeth (pulp, dentin, enamel)
* Amelogenesis imperfecta
* Ankylosis
* Anodontia
* Caries
* Early childhood caries
* Concrescence
* Failure of eruption of teeth
* Dens evaginatus
* Talon cusp
* Dentin dysplasia
* Dentin hypersensitivity
* Dentinogenesis imperfecta
* Dilaceration
* Discoloration
* Ectopic enamel
* Enamel hypocalcification
* Enamel hypoplasia
* Turner's hypoplasia
* Enamel pearl
* Fluorosis
* Fusion
* Gemination
* Hyperdontia
* Hypodontia
* Maxillary lateral incisor agenesis
* Impaction
* Wisdom tooth impaction
* Macrodontia
* Meth mouth
* Microdontia
* Odontogenic tumors
* Keratocystic odontogenic tumour
* Odontoma
* Dens in dente
* Open contact
* Premature eruption
* Neonatal teeth
* Pulp calcification
* Pulp stone
* Pulp canal obliteration
* Pulp necrosis
* Pulp polyp
* Pulpitis
* Regional odontodysplasia
* Resorption
* Shovel-shaped incisors
* Supernumerary root
* Taurodontism
* Trauma
* Avulsion
* Cracked tooth syndrome
* Vertical root fracture
* Occlusal
* Tooth loss
* Edentulism
* Tooth wear
* Abrasion
* Abfraction
* Acid erosion
* Attrition
Periodontium (gingiva, periodontal ligament, cementum, alveolus) – Gums and tooth-supporting structures
* Cementicle
* Cementoblastoma
* Gigantiform
* Cementoma
* Eruption cyst
* Epulis
* Pyogenic granuloma
* Congenital epulis
* Gingival enlargement
* Gingival cyst of the adult
* Gingival cyst of the newborn
* Gingivitis
* Desquamative
* Granulomatous
* Plasma cell
* Hereditary gingival fibromatosis
* Hypercementosis
* Hypocementosis
* Linear gingival erythema
* Necrotizing periodontal diseases
* Acute necrotizing ulcerative gingivitis
* Pericoronitis
* Peri-implantitis
* Periodontal abscess
* Periodontal trauma
* Periodontitis
* Aggressive
* As a manifestation of systemic disease
* Chronic
* Perio-endo lesion
* Teething
Periapical, mandibular and maxillary hard tissues – Bones of jaws
* Agnathia
* Alveolar osteitis
* Buccal exostosis
* Cherubism
* Idiopathic osteosclerosis
* Mandibular fracture
* Microgenia
* Micrognathia
* Intraosseous cysts
* Odontogenic: periapical
* Dentigerous
* Buccal bifurcation
* Lateral periodontal
* Globulomaxillary
* Calcifying odontogenic
* Glandular odontogenic
* Non-odontogenic: Nasopalatine duct
* Median mandibular
* Median palatal
* Traumatic bone
* Osteoma
* Osteomyelitis
* Osteonecrosis
* Bisphosphonate-associated
* Neuralgia-inducing cavitational osteonecrosis
* Osteoradionecrosis
* Osteoporotic bone marrow defect
* Paget's disease of bone
* Periapical abscess
* Phoenix abscess
* Periapical periodontitis
* Stafne defect
* Torus mandibularis
Temporomandibular joints, muscles of mastication and malocclusions – Jaw joints, chewing muscles and bite abnormalities
* Bruxism
* Condylar resorption
* Mandibular dislocation
* Malocclusion
* Crossbite
* Open bite
* Overbite
* Overeruption
* Overjet
* Prognathia
* Retrognathia
* Scissor bite
* Maxillary hypoplasia
* Temporomandibular joint dysfunction
Salivary glands
* Benign lymphoepithelial lesion
* Ectopic salivary gland tissue
* Frey's syndrome
* HIV salivary gland disease
* Necrotizing sialometaplasia
* Mucocele
* Ranula
* Pneumoparotitis
* Salivary duct stricture
* Salivary gland aplasia
* Salivary gland atresia
* Salivary gland diverticulum
* Salivary gland fistula
* Salivary gland hyperplasia
* Salivary gland hypoplasia
* Salivary gland neoplasms
* Benign: Basal cell adenoma
* Canalicular adenoma
* Ductal papilloma
* Monomorphic adenoma
* Myoepithelioma
* Oncocytoma
* Papillary cystadenoma lymphomatosum
* Pleomorphic adenoma
* Sebaceous adenoma
* Malignant: Acinic cell carcinoma
* Adenocarcinoma
* Adenoid cystic carcinoma
* Carcinoma ex pleomorphic adenoma
* Lymphoma
* Mucoepidermoid carcinoma
* Sclerosing polycystic adenosis
* Sialadenitis
* Parotitis
* Chronic sclerosing sialadenitis
* Sialectasis
* Sialocele
* Sialodochitis
* Sialosis
* Sialolithiasis
* Sjögren's syndrome
Orofacial soft tissues – Soft tissues around the mouth
* Actinomycosis
* Angioedema
* Basal cell carcinoma
* Cutaneous sinus of dental origin
* Cystic hygroma
* Gnathophyma
* Ludwig's angina
* Macrostomia
* Melkersson–Rosenthal syndrome
* Microstomia
* Noma
* Oral Crohn's disease
* Orofacial granulomatosis
* Perioral dermatitis
* Pyostomatitis vegetans
Other
* Eagle syndrome
* Hemifacial hypertrophy
* Facial hemiatrophy
* Oral manifestations of systemic disease
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Cyclic neutropenia | c0221023 | 3,671 | wikipedia | https://en.wikipedia.org/wiki/Cyclic_neutropenia | 2021-01-18T18:50:39 | {"gard": ["6229"], "mesh": ["C536227"], "umls": ["C0221023"], "orphanet": ["2686"], "wikidata": ["Q5198214"]} |
Aminoacylase 1 deficiency
Other namesNeurological conditions associated with aminoacylase 1 deficiency
Aminoacylase 1 deficiency is inherited in an autosomal recessive manner
Aminoacylase 1 deficiency is a rare inborn error of metabolism. To date only 21 cases have been described.[1][2]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Molecular biology
* 4 Diagnosis
* 5 Treatment
* 6 History
* 7 References
* 8 External links
## Signs and symptoms[edit]
The clinical picture is heterogeneous and includes motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features.
## Genetics[edit]
This disorder in inherited in an autosomal recessive fashion.
## Molecular biology[edit]
Aminoacylase 1 (ACY1: EC 3.5.14) is a zinc binding enzyme which hydrolyzes N-acetyl amino acids into the free amino acid and acetic acid. Of the N-acetyl amino hydrolyzing enzymes, aminoacylase 1 is the most common.
The ACY1 gene is located on the short arm of chromosome 3 (3p21.2).
## Diagnosis[edit]
There is a specific pattern of N-acetyl amino acid excretion in the urine. The diagnosis can be confirmed by sequencing of the aminoacylase 1 gene.
## Treatment[edit]
This section is empty. You can help by adding to it. (November 2017)
## History[edit]
This disorder was first reported in 2005.[3]
## References[edit]
1. ^ Ferri L, Funghini S, Fioravanti A, Biondi E, La Marca G, Guerrini R, Donati M, Morrone A (2013) Aminoacylase I deficiency due to ACY1 mRNA exon skipping. Clin Genet doi: 10.1111/cge.12297
2. ^ Sass JO, Mohr V, Olbrich H, Engelke U, Horvath J, Fliegauf M, Loges NT, Schweitzer-Krantz S, Moebus R, Weiler P, Kispert A, Superti-Furga A, Wevers RA, Omran H (2006) Mutations in ACY1, the gene encoding aminoacylase 1, cause a novel inborn error of metabolism. Am J Hum Genet 78(3):401-409
3. ^ Van Coster RN, Gerlo EA, Giardina TG, Engelke UF, Smet JE, De Praeter CM, Meersschaut VA, De Meirleir LJ, Seneca SH, Devreese B, Leroy JG, Herga S, Perrier JP, Wevers RA, Lissens W (2005) Aminoacylase I deficiency: a novel inborn error of metabolism. Biochem Biophys Res Commun 338(3):1322-1326
## External links[edit]
Classification
D
* ICD-10: E72.8
* OMIM: 609924
* MeSH: C538246
External resources
* Orphanet: 137754
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Aminoacylase 1 deficiency | c1835922 | 3,672 | wikipedia | https://en.wikipedia.org/wiki/Aminoacylase_1_deficiency | 2021-01-18T18:58:55 | {"gard": ["9741"], "mesh": ["C538246"], "umls": ["C1835922"], "orphanet": ["137754"], "wikidata": ["Q28208917"]} |
Umbilical cord ulceration and intestinal atresia
Other namesUmbilical cord ulcer with intestinal atresia[1]
SpecialtyGastroenterology
Umbilical cord ulceration and intestinal atresia is a rare[1] congenital disease that leads to intestinal atresia, umbilical cord ulceration and severe intrauterine haemorrhage. Only 15 cases have so far been reported,[2] though newer studies are beginning to conclude that this disease has a higher incidence rate than has been previously reported.[3] A particular study has given intestinal atresia and umbilical cord ulceration a clear link after 5 such cases were reported at the time of publication.[4]
## References[edit]
1. ^ a b Umbilical cord ulceration and intestinal atresia at NIH's Office of Rare Diseases
2. ^ "Umbilical cord ulceration intestinal atresia". Orphanet. September 2006. ORPHA3405.
3. ^ Ohyama M, Itani Y, Yamanaka M, et al. (May 2000). "Umbilical cord ulcer: a serious in utero complication of intestinal atresia". Placenta. 21 (4): 432–5. doi:10.1053/plac.1999.0480. PMID 10833382.
4. ^ Yamanaka M, Ohyama M, Koresawa M, Kawataki M, Ohsaki I, Tanaka Y (December 1996). "Umbilical cord ulceration and intestinal atresia". Eur. J. Obstet. Gynecol. Reprod. Biol. 70 (2): 209–12. doi:10.1016/S0301-2115(95)02559-6. PMID 9119106.
## External links[edit]
Classification
D
* MeSH: C536938
External resources
* Orphanet: 3405
This article about a disorder arising in the perinatal period is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Umbilical cord ulceration and intestinal atresia | c2931371 | 3,673 | wikipedia | https://en.wikipedia.org/wiki/Umbilical_cord_ulceration_and_intestinal_atresia | 2021-01-18T18:37:14 | {"gard": ["5403"], "mesh": ["C536938"], "umls": ["C2931371"], "orphanet": ["3405"], "wikidata": ["Q7881317"]} |
A number sign (#) is used with this entry because of evidence that hereditary prostate cancer-1 (HPC1) is caused by heterozygous germline mutation in the gene encoding ribonuclease L (RNASEL; 180435) on chromosome 1q25.
For a general discussion of hereditary prostate cancer, see 176807.
Mapping
Smith et al. (1996) noted that segregation analysis of familial prostate cancer suggests the existence of at least 1 dominant susceptibility locus and predicts that high-risk alleles at such loci account in the aggregate for 9% of all prostate cancers and for more than 40% of early-onset disease. They stated further that prostate cancer presents a number of serious obstacles to linkage analysis, including occurrence of phenocopies, late age of onset, and absence of clinical features that might allow subgrouping to reflect potential genetic heterogeneity. Smith et al. (1996) undertook linkage analysis in 79 North American and 12 Swedish pedigrees, each having at least 3 first-degree relatives with prostate cancer. In these families there was also evidence of bilineal inheritance. Affected individuals had an average age at diagnosis of 65 years, with a total of 34 men diagnosed before the age of 55. The investigators analyzed a total of 341 dinucleotide repeat markers in a subgroup of 66 North American families. For the parametric analysis of the data they used a model of dominant inheritance that included a fixed phenocopy rate of 15% and the assumption that unaffected men over 75 were not likely to be gene carriers. The highest lod score observed was 2.75 with the marker D1S218, which maps to the distal long arm of chromosome 1 at 1q24-q25. The investigators then typed additional markers in this region in all 79 North American families and the 12 Swedish families. This analysis provided additional evidence for linkage with a maximum 2-point lod score of 3.65 at theta = 0.18 with marker D1S2883. Significant evidence for locus heterogeneity was obtained by an admixture test, which estimated that 34% of families were linked to the 1q24-q25 region. The maximum multipoint lod score with markers D1S2883, D1S158, and D1S422 under the assumption of heterogeneity was 5.43, with the postulated susceptibility locus mapping close to D1S422. Smith et al. (1996) found no clinical features that appeared to distinguish families showing linkage to chromosome 1 from unlinked families. They noted that Cher et al. (1996) reported that a large portion of chromosome 1, including 1q24-q25, is frequently increased in copy number in advanced prostate cancer specimens examined by comparative genomic hybridization. Smith et al. (1996) proposed the designation of HPC1 (hereditary prostate cancer 1) for the locus. They emphasized that early diagnosis can be life-saving in prostate cancer and that the potential ability to identify individuals at high genetic risk, when combined with physical exam, transrectal ultrasound, and prostate-specific antigen (176820) analysis, could ultimately be of significant medical benefit.
McIndoe et al. (1997) reported results of linkage analysis in the region of the putative HPC1 locus on 1q24-q25. The study was part of the Prostate Cancer Genetic Research Study (PROGRESS) at the Fred Hutchinson Cancer Research Center in Seattle. Analysis by 2 parametric methods and 1 nonparametric method failed to confirm linkage to this region. Additionally, they were unable to demonstrate heterogeneity within the dataset.
Cooney et al. (1997) confirmed 1q24-q25 as a likely location of a prostate cancer susceptibility gene. Nonparametric multipoint linkage analysis of data on 6 polymorphic marker sequences covering the candidate chromosomal region were performed in 59 unrelated families selected for analysis on the sole criterion that more than 1 living family member was affected by prostate cancer. In the entire set of 59 families, tight linkage to D1S466 was found; maximum lod = 1.58. In 20 families fulfilling more rigorous criteria, i.e., 3 or more affected individuals within one nuclear family, affected individuals in 3 successive generations, and/or clustering of 2 or more individuals affected before the age of 55 years a maximum lod score of 1.72 was observed with the same marker. The 6 African American families in this study contributed disproportionately to the observation of linkage, with a maximum nonparametric linkage (NPL) Z score at marker D1S158 of 1.39.
Using both parametric and nonparametric methods, Eeles et al. (1998) attempted to confirm the assignment of a locus (HPC1) to 1q in a study of 60 affected related pairs and 76 families with 3 or more cases of prostate cancer, but could find no significant evidence of linkage. The estimated proportion of linked families, under a standard autosomal dominant model, was 4%, with an upper 95% confidence limit of 31%. They concluded that the HPC1 locus is responsible for only a minority of familial prostate cancer cases and that it is likely to be most important in families with at least 4 cases of the disease.
The original study of Smith et al. (1996) mapping the HPC1 gene to 1q24-q25 involved 91 North American and Swedish families, each with multiple cases of prostate cancer. Gronberg et al. (1999) analyzed 40 (12 original and 28 newly identified) Swedish families with hereditary prostate cancer that, on the basis of 40 markers spanning a 25-cM interval within 1q24-q25, showed evidence of linkage. In the complete set of families, a maximum 2-point lod score of 1.10 was observed at D1S413 (at a recombination fraction of 0.1), with a maximum NPL Z score of 1.64 at D1S202 (P = 0.5). The evidence for linkage to this region originated almost exclusively from a subset of 12 early-onset (age less than 65 years) families, which yielded a maximum lod score of 2.38 at D1S413 (theta = 0.0) and an NPL Z score of 1.95 at D1S422 (P = 0.3). Estimates from heterogeneity tests suggested that, within Sweden, as many as 50% of early-onset families have linkage to the HPC1 region.
Neuhausen et al. (1999) examined evidence for linkage to the 1q24-q25 region in a set of 41 extended multicase prostate cancer pedigrees from Utah containing 440 members with prostate cancer. In comparison with the families reported in the initial localization by Smith et al. (1996), the Utah pedigrees were generally much larger (average of 10.7 vs 5.1 cases) and had an older average age at diagnosis (69 vs 65 years). The authors found that the youngest quartile (by median age at diagnosis) yielded a maximum lod of 2.82, P = 0.0003 (at D1S215 to D1S222), compared with a maximum lod of 0.73, P = 0.07 for the oldest quartile pedigrees at the same locus.
In a combined analysis for 6 markers in the 1q24-q25 region in 772 families segregating hereditary prostate cancer, Xu and the International Consortium for Prostate Cancer Genetics (2000) found some evidence for linkage with a peak parametric multipoint lod score assuming heterogeneity (hlod) of 1.4 (p = 0.01) at D1S212. In a subset of 491 families with male-to-male disease transmission, the hlod score was 2.56 (p = 0.0006) whereas the score was zero in the remaining 281 families. The authors stated that the results supported the finding of a prostate cancer susceptibility gene linked to 1q24-q25 in a defined subset of families in which several members are affected at an early age and in which there is male-to-male transmission.
Cancel-Tassin et al. (2001) examined evidence for linkage to the HPC1 locus in 64 (37 previously reported and 27 newly identified) families from southern and western Europe with at least 3 affected individuals with prostate cancer and an average age at diagnosis of 66.4 years. Using both parametric and nonparametric linkage methods, no significant evidence of linkage was observed. A subset of 25 families with earlier age of diagnosis (under 66 years) also showed negative lod scores. Under the assumption of heterogeneity, low positive lod scores were obtained in a small proportion of families.
Molecular Genetics
By a positional cloning/candidate gene method, Carpten et al. (2002) identified the ribonuclease L gene (180435) as the site of germline mutations in 2 HPC1-linked families. Inactive RNASEL alleles are present at a low frequency in the general population. RNASEL regulates cell proliferation and apoptosis through the interferon-regulated 2-5A pathway, and it had been a suggested tumor suppressor gene. In that connection, Carpten et al. (2002) found that microdissected tumors with a germline mutation showed loss of heterozygosity and loss of RNase L protein, and that RNASEL activity was reduced in lymphoblasts from heterozygous individuals compared with family members who were homozygous with respect to the wildtype allele. Thus, germline mutations in RNASEL may be of diagnostic value, and the 2-5A pathway may provide opportunities for developing therapies for those with prostate cancer.
Oncology \- Prostate cancer Inheritance \- Autosomal dominant form ▲ Close
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| PROSTATE CANCER, HEREDITARY, 1 | c2931456 | 3,674 | omim | https://www.omim.org/entry/601518 | 2019-09-22T16:14:39 | {"doid": ["10283"], "mesh": ["C537243"], "omim": ["601518"], "orphanet": ["1331"], "synonyms": ["Alternative titles", "PRCA1"]} |
Isolated ectopia lentis (IEL) is a genetic disorder that affects the positioning of the lens in the eyes. In individuals with IEL, the lens in one or both of the eyes is off-center. Symptoms of IOL usually present in childhood and may include vision problems such as nearsightedness (myopia), blurred vision (astigmatism), clouding of the lenses (cataracts), and increased pressure in the eyes (glaucoma). In some individuals, IEL can progress to retinal detachment (tearing of the back lining of the eye). IEL is caused by mutations in either the FBN1 or ADAMTSL4 gene. When caused by a mutation in the FBN1 gene, IEL is inherited in an autosomal dominant manner. When caused by a mutation in the ADAMTSL4 gene, IEL is inherited in an autosomal recessive manner. The primary goal of treatment is preventing amblyopia (lazy eye) through early correction of astigmatism. Surgical intervention including lensectomy (removal of the lens) may be considered in cases where vision is significantly affected.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Isolated ectopia lentis | c0013581 | 3,675 | gard | https://rarediseases.info.nih.gov/diseases/12251/isolated-ectopia-lentis | 2021-01-18T17:59:42 | {"mesh": ["D004479"], "omim": ["129600", "225100"], "orphanet": ["1885"], "synonyms": ["Ectopia lentis syndrome", "Familial ectopia lentis"]} |
Balkan endemic nephropathy
Other namesDanubian endemic familial nephropathy
Areas in the Balkans with high prevalence
SpecialtyNephrology
Balkan endemic nephropathy[1] (BEN) is a form of interstitial nephritis causing kidney failure. It was first identified in the 1920s among several small, discrete communities along the Danube River and its major tributaries, in the modern countries of Croatia, Bosnia and Herzegovina, Serbia, Romania, and Bulgaria. It is caused by small long-term doses of aristolochic acid in the diet. The disease primarily affects people 30 to 60 years of age. Doses of the toxin are usually low and people moving to endemic areas typically develop the condition only when they have lived there for 10-20 years. People taking higher doses of aristolochic acid (as Chinese herbal supplements) have developed kidney failure after shorter durations of exposure.[2]
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 History
* 4 See also
* 5 References
* 6 External links
## Signs and symptoms[edit]
The patients are distinguished from those suffering from other causes of end-stage renal disease by showing an absence of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure.[3] There is no specific therapy; BEN causes end-stage renal disease, for which the only effective treatments are dialysis or a kidney transplant. In endemic areas BEN is responsible for up to 70% of end-stage renal disease. At least 25,000 individuals are known to have this form of the disease.[4]
Patients with BEN have a greatly increased rate of transitional cell carcinoma of the upper urothelial tract, (the renal pelvis and ureters). (In populations without BEN, most urothelial cancer occurs in the bladder.[5] )
## Causes[edit]
Dietary exposure to aristolochic acid is the cause of BEN and its attendant transitional cell cancers.[6][7] Former hypotheses that included roles for ochratoxin, poisoning by organic compounds leached from lignite or by heavy metals, viruses, and trace-element deficiencies, are not supported by current evidence.[8] Genetic factors may be involved in determining which persons exposed to aristolochic acid suffer from BEN and which do not.[9]
In the Balkan region, dietary aristolochic acid exposure may come from the consumption of the seeds of Aristolochia clematitis (European birthwort), a plant native to the endemic region, which grows among wheat plants and whose seeds mingle with the wheat used for bread.[10][11] Aristolochic-acid-containing herbal remedies used in traditional Chinese medicine are associated with a related—possibly identical—condition known as "Chinese herbs nephropathy".[12]
Exposure to aristolochic acid is associated with a high incidence of uroepithelial tumorigenesis.[13][14]
## History[edit]
The first official published description of the disease was made by the Bulgarian nephrologist Dr.Yoto Tanchev (1917–2000) and his team in 1956 in the Bulgarian Journal Savremenna Medizina,[15] a priority generally acknowledged by the international nephrological community.[3] Their study was based on a wide screening of inhabitants of the villages around the town of Vratsa, Bulgaria. Their contribution to the understanding of this unusual endemic disease of the kidneys was their description of symptoms which were not typical of common chronic nephritis, i.e., incidence only in adults (no children affected), absence of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure.[citation needed]
A striking feature of the disease is its very localized occurrence. There are approximately ten small areas where it occurs, all of them more or less rural, but nothing seems to connect those areas other than the occurrence of this illness. Tanchev and colleagues suggested that the condition was sui generis. Their initial tentative hypothesis for its cause was intoxication with heavy metals, because the affected villages were supplied with water coming from nearby Vratsa Mountain, a karst-type mountain.[citation needed]
The disease was originally called "Vratsa nephritis," and became known as "Balkan endemic nephropathy" later, after people living in Yugoslavia and Romania were found to be suffering from it as well.[3] But in Bulgaria and in neighbouring countries, the condition is known as "Tanchev's Nephropathy", in homage to Dr. Tanchev's work.[citation needed]
## See also[edit]
* Nephropathy
* Citrinin
* Ochratoxin A
## References[edit]
1. ^ Online Mendelian Inheritance in Man (OMIM): 124100
2. ^ Stiborová, M., Arlt, V.M. & Schmeiser, H.H. Balkan endemic nephropathy: an update on its aetiology. Arch Toxicol 90, 2595–2615 (2016). https://doi.org/10.1007/s00204-016-1819-3
3. ^ a b c Tanchev Y, Dorossiev D (1991). "The first clinical description of Balkan endemic nephropathy (1956) and its validity 35 years later". IARC Sci. Publ. (115): 21–8. PMID 1820335.
4. ^ The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy: A Narrative Review Annals of Internal Medicine 19 March 2013, Vol 158, No. 6
5. ^ Elif Batuman (August 12, 2013). "Poisoned Land: On the trail of a mystery disease in the Balkans". The New Yorker. Retrieved August 23, 2013.
6. ^ Grollman AP, Shibutani S, Moriya M, et al. (2007). "Aristolochic acid and the etiology of endemic (Balkan) nephropathy". Proc. Natl. Acad. Sci. U.S.A. 104 (29): 12129–34. Bibcode:2007PNAS..10412129G. doi:10.1073/pnas.0701248104. PMC 1913550. PMID 17620607.
7. ^ Stiborová, M., Arlt, V.M. & Schmeiser, H.H. Balkan endemic nephropathy: an update on its aetiology. Arch Toxicol 90, 2595–2615 (2016). https://doi.org/10.1007/s00204-016-1819-3
8. ^ Stiborová, M., Arlt, V.M. & Schmeiser, H.H. Balkan endemic nephropathy: an update on its aetiology. Arch Toxicol 90, 2595–2615 (2016). https://doi.org/10.1007/s00204-016-1819-3
9. ^ Balkan endemic nephropathy. U.S. Department of Health & Human Services. National Institutes of Health, National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/8576/balkan-endemic-nephropathy
10. ^ Grollman AP, Shibutani S, Moriya M, et al. (2007). "Aristolochic acid and the etiology of endemic (Balkan) nephropathy". Proc. Natl. Acad. Sci. U.S.A. 104 (29): 12129–34. Bibcode:2007PNAS..10412129G. doi:10.1073/pnas.0701248104. PMC 1913550. PMID 17620607.
11. ^ Julia C. Mead (2007). "Manna from hell". The Scientist. 21 (11): 44.
12. ^ De Broe ME (March 2012). "Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy". Kidney Int. 81 (6): 513–5. doi:10.1038/ki.2011.428. PMID 22373701.
13. ^ Ronco, Claudio; et al., eds. (2008). Critical care nephrology. Elsevier Health Sciences. p. 1699. ISBN 978-1-4160-4252-5.
14. ^ Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, Pu YS, Grollman AP (May 2012). "Aristolochic acid-associated urothelial cancer in Taiwan". Proc. Natl. Acad. Sci. U.S.A. 109 (21): 8241–6. doi:10.1073/pnas.1119920109. PMC 3361449. PMID 22493262.
15. ^ Tanchev Y, Evstatiev Z, Dorossiev D, Pencheva J, Tzvetkova G. Studies on the nephritides in the District of Vratza. Savremena Medicina 1956; 7: 14–29 (Bulgarian).
## External links[edit]
Classification
D
* ICD-10: N15.0
* OMIM: 124100
* MeSH: D001449
* DiseasesDB: 31409
* v
* t
* e
Kidney disease
Glomerular disease
* See Template:Glomerular disease
Tubules
* Renal tubular acidosis
* proximal
* distal
* Acute tubular necrosis
* Genetic
* Fanconi syndrome
* Bartter syndrome
* Gitelman syndrome
* Liddle's syndrome
Interstitium
* Interstitial nephritis
* Pyelonephritis
* Balkan endemic nephropathy
Vascular
* Renal artery stenosis
* Renal ischemia
* Hypertensive nephropathy
* Renovascular hypertension
* Renal cortical necrosis
General syndromes
* Nephritis
* Nephrosis
* Renal failure
* Acute renal failure
* Chronic kidney disease
* Uremia
Other
* Analgesic nephropathy
* Renal osteodystrophy
* Nephroptosis
* Abderhalden–Kaufmann–Lignac syndrome
* Diabetes insipidus
* Nephrogenic
* Renal papilla
* Renal papillary necrosis
* Major calyx/pelvis
* Hydronephrosis
* Pyonephrosis
* Reflux nephropathy
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*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Balkan endemic nephropathy | c0004698 | 3,676 | wikipedia | https://en.wikipedia.org/wiki/Balkan_endemic_nephropathy | 2021-01-18T18:50:36 | {"gard": ["8576"], "mesh": ["D001449"], "umls": ["C0004698"], "wikidata": ["Q805030"]} |
Ecthyma gangrenosum
SpecialtyInfectious diseases
Ecthyma gangrenosum is a type of skin lesion characterized by vesicles or blisters which rapidly evolve into pustules and necrotic ulcers with undermined tender erythematous border. "Ecthyma" means a pus forming infection of the skin with an ulcer, "gangrenosum" refers to the accompanying gangrene or necrosis. It is classically associated with Pseudomonas aeruginosa bacteremia, but it is not pathognomonic. [1] Pseudomonas aeruginosa is a gram negative, aerobic bacillus.[2]
This type of skin lesion was first described in association with Pseudomonas aeruginosa by L. Barker in 1897.[3] It was given the name "ecthyma gangrenosum" by Hitschmann and Kreibich.[4]
It mostly occurs in patients with underlying immunocompromise (e.g. malignancy or HIV). Although most cases are due to Pseudomonas aeruginosa infection, there are recent reports of this skin lesion in association with other microorganisms, such as Escherichia coli, Citrobacter freundii, Klebsiella pneumoniae, various other Pseudomonas species, and Morganella morganii.[3]
## Contents
* 1 Signs and symptoms
* 2 Mechanism
* 3 Diagnosis
* 4 Prevention
* 5 Treatments
* 6 Recent research
* 7 References
* 8 External links
## Signs and symptoms[edit]
The primary skin lesion usually starts with a macule that is painless, round and erythematous. Then, it develops into a pustule, and then a bulla with central hemorrhagic focus. The bulla progresses into an ulcer which extends laterally. Finally it becomes a gangrenous ulcer with a central black eschar surrounded by an erythematous halo.[4]
The lesions may be single or multiple. They are most commonly seen in perineum and under arm pit. However, they can occur in any part of the body.[4]
## Mechanism[edit]
The organism enters directly through the breakdown of mechanical defense barriers such as mucosa or skin. Conditions which lead to the development of an immunocompromised state make the patient more susceptible to ecthyma gangrenosum and sepsis.[4] In case of sepsis, the bacteria reaches the skin via the bloodstream. Defective humoral or cellular immunity increases risk, as the organism is not cleared from the bloodstream as usual. The main mechanism of the organism that is causing the typical skin lesions is the invasion of the organism into the arteries and veins in the dermis and subcutaneous tissues of the skin. This perivascular invasion leads to nodular formation, ulceration, vasculitis and necrosis due to impaired blood supply. Perivascular involvement is achieved by direct entry of bacteria through the skin or hematogenous spreading in case of sepsis.[4]
## Diagnosis[edit]
Diagnosis is made by clinical observation and the following tests.
(1) Gram stain of the fluid from pustules or bullae, and tissue swab.
(2) Blood culture
(3) Urine culture
(4) Skin biopsy
(5) Tissue culture
Magnetic resonance imaging can be done in case of ecthyma gangrenosum of plantar foot to differentiate from necrotizing fasciitis.[4]
## Prevention[edit]
The main organism associated with ecthyma gangrenosum is Pseudomonas aeruginosa. However, multi-bacterial cases are reported as well. Prevention measures include practicing proper hygiene, educating the immunocompromised patients for awareness to avoid possible conditions and seek timely medical treatment.[4]
## Treatments[edit]
Treatments involve antibiotics that cover for Pseudomonas aeruginosa. antipseudomonal penicillins, aminoglycosides, fluoroquinolones, third generation cephalosporins or aztreonam can be given. Usually, the antibiotics are changed according to the culture and sensitivity result.[4] In patients with very low white blood cell counts, granulocyte-macrophage colony-stimulating factor may be given. Depending on the causal agents, antivirals or antifungals can be added.[4]
Surgery will be needed if there is extensive necrosis not responding to medical treatments.
## Recent research[edit]
A recent retrospective study of all cases of ecthyma gangrenosum from 2004–2010 in a university hospital in Mexico shows that neutropenia in immunocompromised patients is the most common risk factor for ecthyma gangrenosum.[5]
## References[edit]
1. ^ Reich, Hilary L. "Nonpseudomonal ecthyma gangrenosum". Journal of the American Academy of Dermatology. 50 (5): 114. PMID 15097944. Retrieved 11 May 2020.
2. ^ Koo, Su Han; Lee, Joon Ho; Shin, Heakyeong; Lee, Jong Im (2012-11-14). "Ecthyma Gangrenosum in a Previously Healthy Infant". Archives of Plastic Surgery. 39 (6): 673–5. doi:10.5999/aps.2012.39.6.673. ISSN 2234-6163. PMC 3518017. PMID 23233899.
3. ^ a b Vaiman, M.; Lazarovitch, T.; Heller, L.; Lotan, G. (2015-04-01). "Ecthyma gangrenosum and ecthyma-like lesions: review article". European Journal of Clinical Microbiology & Infectious Diseases. 34 (4): 633–639. doi:10.1007/s10096-014-2277-6. ISSN 0934-9723. PMID 25407372.
4. ^ a b c d e f g h i Kingsberry, M. (2017). "Ecthyma gangrenosum: Overview". Medscape.
5. ^ Martínez-Longoria, César Adrián; Rosales-Solis, Gloria María; Ocampo-Garza, Jorge; Guerrero-González, Guillermo Antonio; Ocampo-Candiani, Jorge (October 2017). "Ecthyma gangrenosum: a report of eight cases". Anais Brasileiros de Dermatologia. 92 (5): 698–700. doi:10.1590/abd1806-4841.20175580. ISSN 0365-0596. PMC 5674706. PMID 29166510.
## External links[edit]
Classification
D
* DiseasesDB: 29391
External resources
* eMedicine: derm/539
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Ecthyma gangrenosum | c0276085 | 3,677 | wikipedia | https://en.wikipedia.org/wiki/Ecthyma_gangrenosum | 2021-01-18T18:28:18 | {"umls": ["C0276085"], "wikidata": ["Q5333982"]} |
Anuria
Other namesAnuresis
SpecialtyNephrology
Anuria is nonpassage of urine,[1] in practice is defined as passage of less than 100[2] milliliters of urine in a day.[3] Anuria is often caused by failure in the function of kidneys. It may also occur because of some severe obstruction like kidney stones or tumours. It may occur with end stage kidney disease. It is a more extreme reduction than oliguria (hypouresis), with 100 mL/day being the conventional (albeit slightly arbitrary) cutoff point between the two.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
Anuria itself is a symptom, not a disease. It is often associated with other symptoms of kidney failure, such as lack of appetite, weakness, nausea and vomiting. These are mostly the result of buildup of toxins in the blood which would normally be removed by healthy kidneys.
## Causes[edit]
Failure of kidney function, which can have multiple causes including medications or toxins (e.g., antifreeze, cephalosporins, ACEIs); diabetes; high blood pressure. Stones or tumours in the urinary tract can also cause it by creating an obstruction to urinary flow. High blood calcium, oxalate, or uric acid, can contribute to the risk of stone formation. In males, an enlarged prostate gland is a common cause of obstructive anuria.
Acute anuria, where the decline in urine production occurs quickly, is usually a sign of obstruction or acute kidney failure. Acute kidney failure can be caused by factors not related to the kidney, such as heart failure, mercury poisoning, infection, and other conditions that cause the kidney to be deprived of blood flow.
## Treatment[edit]
Treatment is dependent on the underlying cause of this symptom. The most easily treatable cause is obstruction of urine flow, which is often solved by insertion of a urinary catheter into the urinary bladder.
Mannitol is a medicine that is used to increase the amount of water removed from the blood and thus improve the blood flow to the kidneys. However, mannitol is contraindicated in anuria secondary to renal disease, severe dehydration, intracranial bleeding (except during craniotomy), severe pulmonary congestion, or pulmonary edema.
Dextrose and dobutamine are both used to increase blood flow to the kidney and act within 30 to 60 minutes.
## References[edit]
1. ^ "anuria" at Dorland's Medical Dictionary
2. ^ Harrison's Principles of Internal Medicine, 19E PAGE 292
3. ^ "SUNY Stony Brook Pathology Department HBP310 Inflammation". Archived from the original on 2009-04-27. Retrieved 2009-06-15.
## External links[edit]
Classification
D
* ICD-10: R34
* ICD-9-CM: 788.5
* MeSH: D001002
* DiseasesDB: 23641
* v
* t
* e
Symptoms and signs relating to the urinary system
Pain
* Dysuria
* Renal colic
* Costovertebral angle tenderness
* Vesical tenesmus
Control
* Urinary incontinence
* Enuresis
* Diurnal enuresis
* Giggling
* Nocturnal enuresis
* Post-void dribbling
* Stress
* Urge
* Overflow
* Urinary retention
Volume
* Oliguria
* Anuria
* Polyuria
Other
* Lower urinary tract symptoms
* Nocturia
* urgency
* frequency
* Extravasation of urine
* Uremia
Eponymous
* Addis count
* Brewer infarcts
* Lloyd's sign
* Mathe's sign
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Anuria | c0003460 | 3,678 | wikipedia | https://en.wikipedia.org/wiki/Anuria | 2021-01-18T18:29:56 | {"mesh": ["D001002"], "umls": ["C0003460"], "icd-9": ["788.5"], "icd-10": ["R33"], "wikidata": ["Q612681"]} |
Neutropenic enterocolitis
Other namesTyphlitis, typhlenteritis, caecitis, cecitis
SpecialtyGeneral surgery
Neutropenic enterocolitis is inflammation of the cecum (part of the large intestine) that may be associated with infection.[1] It is particularly associated with neutropenia, a low level of neutrophil granulocytes (the most common form of white blood cells) in the blood.
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 4 Treatment
* 5 Prognosis
* 6 See also
* 7 References
* 8 External links
## Signs and symptoms[edit]
Signs and symptoms of typhlitis may include diarrhea, a distended abdomen, fever, chills, nausea, vomiting, and abdominal pain or tenderness.[2]
## Cause[edit]
The condition is usually caused by Gram-positive enteric commensal bacteria of the gut (gut flora). Clostridium difficile is a species of Gram-positive bacteria that commonly causes severe diarrhea and other intestinal diseases when competing bacteria are wiped out by antibiotics, causing pseudomembranous colitis, whereas Clostridium septicum is responsible for most cases of neutropenic enterocolitis.[3]
Typhlitis most commonly occurs in immunocompromised patients, such as those undergoing chemotherapy,[4] patients with AIDS, kidney transplant patients, or the elderly.[2]
## Diagnosis[edit]
Typhlitis is diagnosed with a radiograph CT scan showing thickening of the cecum and "fat stranding".[citation needed]
## Treatment[edit]
Typhlitis is a medical emergency and requires prompt management. Untreated typhlitis has a poor prognosis, particularly if associated with pneumatosis intestinalis (air in the bowel wall) and/or bowel perforation, and has significant morbidity unless promptly recognized and aggressively treated.[4]
Successful treatment hinges on:
1. Early diagnosis provided by a high index of suspicion and the use of CT scanning
2. Nonoperative treatment for uncomplicated cases
3. Empiric antibiotics, particularly if the patient is neutropenic or at other risk of infection.
In rare cases of prolonged neutropenia and complications such as bowel perforation, neutrophil transfusions can be considered but have not been studied in a randomized control trial. Elective right hemicolectomy may be used to prevent recurrence but is generally not recommended[citation needed]
"...The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however," as based on studies from the 1980s[4]
## Prognosis[edit]
Inflammation can spread to other parts of the gut in patients with typhlitis.[citation needed] The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.[5]
Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation.[2] More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death [6] .
## See also[edit]
* Colitis
## References[edit]
1. ^ Definition at thefreedictionary.com
2. ^ a b c Stoer TM, Koslin DB (2004). "Typhlitis Imaging". Medscape. WebMD LLC. Retrieved September 3, 2016.
3. ^ King A, Rampling A, Wight DG, Warren RE (1984). "Neutropenic enterocolitis due to Clostridium septicum infection". J Clin Pathol. 37 (3): 335–43. doi:10.1136/jcp.37.3.335. PMC 498711. PMID 6699196.
4. ^ a b c Keidan RD, Fanning J, Gatenby RA, Weese JL (Mar 1989). "Recurrent typhlitis. A disease resulting from aggressive chemotherapy". Dis Colon Rectum. 32 (3): 206–9. doi:10.1007/BF02554529. PMID 2920627.
5. ^ Boggio L, Pooley R, Winter JN (February 2000). "Typhlitis complicating autologous blood stem cell transplantation for breast cancer". Nature. Macmillan Publishers Limited. 25 (3): 321–6. doi:10.1038/sj.bmt.1702134. PMID 10673706.
6. ^ Shafey, A; et al. (October 2013). "Incidence, risk factors, and outcomes of enteritis, typhlitis, and colitis in children with acute leukemia". J Pediatr Hematol Oncol. 35 (7): 514–7. doi:10.1097/MPH.0b013e31829f3259. PMID 23823116.
## External links[edit]
Classification
D
* ICD-9-CM: 540.0 540.9 541
* MeSH: D020345
* DiseasesDB: 31505
External resources
* eMedicine: radio/869
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
* Gastroenteritis
* Peptic (gastric) ulcer
* Cushing ulcer
* Dieulafoy's lesion
* Dyspepsia
* Pyloric stenosis
* Achlorhydria
* Gastroparesis
* Gastroptosis
* Portal hypertensive gastropathy
* Gastric antral vascular ectasia
* Gastric dumping syndrome
* Gastric volvulus
* Buried bumper syndrome
* Gastrinoma
* Zollinger–Ellison syndrome
Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
* Duodenitis
* Jejunitis
* Ileitis
* Peptic (duodenal) ulcer
* Curling's ulcer
* Malabsorption: Coeliac
* Tropical sprue
* Blind loop syndrome
* Small bowel bacterial overgrowth syndrome
* Whipple's
* Short bowel syndrome
* Steatorrhea
* Milroy disease
* Bile acid malabsorption
Large intestine
(Appendix/Colon)
* Appendicitis
* Colitis
* Pseudomembranous
* Ulcerative
* Ischemic
* Microscopic
* Collagenous
* Lymphocytic
* Functional colonic disease
* IBS
* Intestinal pseudoobstruction / Ogilvie syndrome
* Megacolon / Toxic megacolon
* Diverticulitis/Diverticulosis/SCAD
Large and/or small
* Enterocolitis
* Necrotizing
* Gastroenterocolitis
* IBD
* Crohn's disease
* Vascular: Abdominal angina
* Mesenteric ischemia
* Angiodysplasia
* Bowel obstruction: Ileus
* Intussusception
* Volvulus
* Fecal impaction
* Constipation
* Diarrhea
* Infectious
* Intestinal adhesions
Rectum
* Proctitis
* Radiation proctitis
* Proctalgia fugax
* Rectal prolapse
* Anismus
Anal canal
* Anal fissure/Anal fistula
* Anal abscess
* Hemorrhoid
* Anal dysplasia
* Pruritus ani
GI bleeding
* Blood in stool
* Upper
* Hematemesis
* Melena
* Lower
* Hematochezia
Accessory
Liver
* Hepatitis
* Viral hepatitis
* Autoimmune hepatitis
* Alcoholic hepatitis
* Cirrhosis
* PBC
* Fatty liver
* NASH
* Vascular
* Budd–Chiari syndrome
* Hepatic veno-occlusive disease
* Portal hypertension
* Nutmeg liver
* Alcoholic liver disease
* Liver failure
* Hepatic encephalopathy
* Acute liver failure
* Liver abscess
* Pyogenic
* Amoebic
* Hepatorenal syndrome
* Peliosis hepatis
* Metabolic disorders
* Wilson's disease
* Hemochromatosis
Gallbladder
* Cholecystitis
* Gallstone / Cholelithiasis
* Cholesterolosis
* Adenomyomatosis
* Postcholecystectomy syndrome
* Porcelain gallbladder
Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
* Secondary sclerosing cholangitis
* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
* Haemobilia
* Common bile duct
* Choledocholithiasis
* Biliary dyskinesia
* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
* Chronic
* Hereditary
* Pancreatic abscess
* Pancreatic pseudocyst
* Exocrine pancreatic insufficiency
* Pancreatic fistula
Other
Hernia
* Diaphragmatic
* Congenital
* Hiatus
* Inguinal
* Indirect
* Direct
* Umbilical
* Femoral
* Obturator
* Spigelian
* Lumbar
* Petit's
* Grynfeltt-Lesshaft
* Undefined location
* Incisional
* Internal hernia
* Richter's
Peritoneal
* Peritonitis
* Spontaneous bacterial peritonitis
* Hemoperitoneum
* Pneumoperitoneum
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Neutropenic enterocolitis | c0267537 | 3,679 | wikipedia | https://en.wikipedia.org/wiki/Neutropenic_enterocolitis | 2021-01-18T19:07:51 | {"mesh": ["D053706"], "umls": ["C0267537"], "icd-9": ["540.0", "541", "540.9"], "wikidata": ["Q462339"]} |
The transitional form of Pelizaeus-Merzbacher disease (PMD) is the intermediate form of PMD (see this term).
## Epidemiology
PMD has an estimated prevalence of 1/400,000. The transitional form accounts for about 15% of all cases of PMD. It predominantly affects males.
## Clinical description
The predominant clinical findings are early-onset nystagmus, initial hypotonia that is replaced by spasticity later in life, moderate cognitive impairment and inability to ambulate.
## Etiology
The transitional form of PMD is most often due to missense mutations of the PLP1 gene (on Xq22) that cause hypomyelination of the central nervous system. Some duplications or triplications of the gene can also cause the transitional form. PLP1 encodes the proteolipid protein (PLP), the most abundant protein of the myelin sheath in the central nervous system, and its alternatively spliced isoform (DM20).
## Genetic counseling
The disease has an X-linked inheritance pattern.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pelizaeus-Merzbacher disease, transitional form | c0751917 | 3,680 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=280224 | 2021-01-23T17:25:05 | {"mesh": ["D020371"], "umls": ["C0751917"], "icd-10": ["E75.2"], "synonyms": ["Transitional PMD"]} |
Neuroblastoma
Microscopic view of a typical neuroblastoma with rosette formation
SpecialtyOncology
SymptomsBone pain, lumps[1]
Usual onsetUnder 5 years old[1]
CausesGenetic mutation[1]
Diagnostic methodTissue biopsy[1]
TreatmentObservation, surgery, radiation, chemotherapy, stem cell transplantation[1]
PrognosisUS five-year survival ~95% (< 1 year old), 68% (1–14 years old)[2]
Frequency1 in 7,000 children[2]
Deaths15% of deaths due to cancer in children[3]
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue.[1] It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine.[1] Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin.[1]
Typically, neuroblastoma occurs due to a genetic mutation occurring during early development.[4] Rarely, it may be due to a mutation inherited from a person's parents.[1] Environmental factors have not been found to be involved.[2] Diagnosis is based on a tissue biopsy.[1] Occasionally, it may be found in a baby by ultrasound during pregnancy.[1] At diagnosis, the cancer has usually already spread.[1] The cancer is divided into low-, intermediate-, and high-risk groups based on a child's age, cancer stage, and what the cancer looks like.[1]
Treatment and outcomes depends on the risk group a person is in.[1][4] Treatments may include observation, surgery, radiation, chemotherapy, or stem cell transplantation.[1] Low-risk disease in babies typically has a good outcome with surgery or simply observation.[4] In high-risk disease, chances of long-term survival, however, are less than 40%, despite aggressive treatment.[4]
Neuroblastoma is the most common cancer in babies and the third-most common cancer in children after leukemia and brain cancer.[4] About one in every 7,000 children is affected at some time.[2] About 90% of cases occur in children less than 5 years old, and it is rare in adults.[2][3] Of cancer deaths in children, about 15% are due to neuroblastoma.[3] The disease was first described in the 1800s.[5]
## Contents
* 1 Signs and symptoms
* 2 Cause
* 3 Diagnosis
* 3.1 Biochemistry
* 3.2 Imaging
* 3.3 Histology
* 3.4 Staging
* 4 Screening
* 5 Treatment
* 6 Prognosis
* 6.1 Cytogenetic profiles
* 7 Epidemiology
* 8 History
* 9 Society and culture
* 9.1 Legislative efforts
* 10 Research
* 10.1 Preclinical models
* 10.2 Treatments
* 10.3 Refractory and relapsed neuroblastoma
* 11 References
* 12 External links
## Signs and symptoms[edit]
The first symptoms of neuroblastoma are often vague, making diagnosis difficult. Fatigue, loss of appetite, fever, and joint pain are common. Symptoms depend on primary tumor locations and metastases if present:[6]
* In the abdomen, a tumor may cause a swollen belly and constipation.
* A tumor in the chest may cause breathing problems.
* A tumor pressing on the spinal cord may cause weakness, thus an inability to stand, crawl, or walk.
* Bone lesions in the legs and hips may cause pain and limping.
* A tumor in the bones around the eyes or orbits may cause distinct bruising and swelling.
* Infiltration of the bone marrow may cause pallor from anemia.
Neuroblastoma often spreads to other parts of the body before any symptoms are apparent, and 50 to 60% of all neuroblastoma cases present with metastases.[7]
The most common location for neuroblastoma to originate (i.e., the primary tumor) is in the adrenal glands. This occurs in 40% of localized tumors and in 60% of cases of widespread disease. Neuroblastoma can also develop anywhere along the sympathetic nervous system chain from the neck to the pelvis. Frequencies in different locations include: neck (1%), chest (19%), abdomen (30% nonadrenal), or pelvis (1%). In rare cases, no primary tumor can be discerned.[8]
Rare but characteristic presentations include transverse myelopathy (tumor spinal cord compression, 5% of cases), treatment-resistant diarrhea (tumor vasoactive intestinal peptide secretion, 4% of cases), Horner's syndrome (cervical tumor, 2.4% of cases), opsoclonus myoclonus syndrome[9] and ataxia (suspected paraneoplastic cause, 1.3% of cases), and hypertension (catecholamine secretion or kidney artery compression, 1.3% of cases).[10]
## Cause[edit]
The cause of neuroblastoma is not well understood. The great majority of cases are sporadic and nonfamilial. About 1–2% of cases run in families and have been linked to specific gene mutations. Familial neuroblastoma in some cases is caused by rare germline mutations in the anaplastic lymphoma kinase (ALK) gene.[11] Germline mutations in the PHOX2B or KIF1B gene have been implicated in familial neuroblastoma, as well. Neuroblastoma is also a feature of neurofibromatosis type 1 and the Beckwith-Wiedemann syndrome.
MYCN oncogene amplification within the tumor is a common finding in neuroblastoma. The degree of amplification shows a bimodal distribution: either 3- to 10-fold, or 100- to 300-fold. The presence of this mutation is highly correlated to advanced stages of disease.[12]
Duplicated segments of the LMO1 gene within neuroblastoma tumor cells have been shown to increase the risk of developing an aggressive form of the cancer.[13]
Neuroblastoma has been linked to copy-number variation within the NBPF10 gene, which results in the 1q21.1 deletion syndrome or 1q21.1 duplication syndrome.[14]
Several risk factors have been proposed and are the subject of ongoing research. Due to characteristic early onset, many studies have focused on parental factors around conception and during gestation. Factors investigated have included occupation (i.e. exposure to chemicals in specific industries), smoking, alcohol consumption, use of medicinal drugs during pregnancy, and birth factors; however, results have been inconclusive.[15]
Other studies have examined possible links with atopy and exposure to infection early in life,[16] use of hormones and fertility drugs,[17] and maternal use of hair dye.[18][19]
## Diagnosis[edit]
MRI showing orbital and skull vault metastatic NB in 2-year-old
The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests. It may arise from any neural crest element of the sympathetic nervous system (SNS).
Esthesioneuroblastoma, also known as olfactory neuroblastoma, is believed to arise from the olfactory epithelium and its classification remains controversial. However, since it is not a sympathetic nervous system malignancy, esthesioneuroblastoma is a distinct clinical entity and is not to be confused with neuroblastoma.[20][21]
### Biochemistry[edit]
In about 90% of cases of neuroblastoma, elevated levels of catecholamines or their metabolites are found in the urine or blood. Catecholamines and their metabolites include dopamine, homovanillic acid (HVA), and/or vanillylmandelic acid (VMA).[22]
### Imaging[edit]
Another way to detect neuroblastoma is the meta-iodobenzylguanidine scan, which is taken up by 90 to 95% of all neuroblastomas, often termed "mIBG-avid".[23] The mechanism is that mIBG is taken up by sympathetic neurons, and is a functioning analog of the neurotransmitter norepinephrine. When it is radio-iodinated with I-131 or I-123 (radioactive iodine isotopes), it is a very good radiopharmaceutical for diagnosis and monitoring of response to treatment for this disease. With a half-life of 13 hours, I-123 is the preferred isotope for imaging sensitivity and quality. I-131 has a half-life of 8 days and at higher doses is an effective therapy as targeted radiation against relapsed and refractory neuroblastoma.[24] As mIBG is not always taken up by neuroblastomas, researchers have explored in children with neuroblastoma whether another type of nuclear imaging, fluoro-deoxy-glucose - positron emission tomography, often termed "F-FDG-PET", might be useful.[25] Evidence suggests that this might be advisable to use in children with neuroblastoma for which mIBG does not work, but more research is needed in this area.[25]
### Histology[edit]
Microscopic view of stroma-rich ganglioneuroblastoma
On microscopy, the tumor cells are typically described as small, round and blue, and rosette patterns (Homer Wright pseudorosettes) may be seen. Homer Wright pseudorosettes are tumor cells around the neuropil, not to be confused with a true rosettes, which are tumor cells around an empty lumen.[26] They are also distinct from the pseudorosettes of an ependymoma which consist of tumor cells with glial fibrillary acidic protein (GFAP)–positive processes tapering off toward a blood vessel (thus a combination of the two).[27] A variety of immunohistochemical stains are used by pathologists to distinguish neuroblastomas from histological mimics, such as rhabdomyosarcoma, Ewing's sarcoma, lymphoma and Wilms' tumor.[28]
Neuroblastoma is one of the peripheral neuroblastic tumors (pNTs) that have similar origins and show a wide pattern of differentiation ranging from benign ganglioneuroma to stroma-rich ganglioneuroblastoma with neuroblastic cells intermixed or in nodules, to highly malignant neuroblastoma. This distinction in the pre-treatment tumor pathology is an important prognostic factor, along with age and mitosis-karyorrhexis index (MKI). This pathology classification system (the Shimada system) describes "favorable" and "unfavorable" tumors by the International Neuroblastoma Pathology Committee (INPC) which was established in 1999 and revised in 2003.[29]
### Staging[edit]
The "International Neuroblastoma Staging System" (INSS) established in 1986 and revised in 1988 stratifies neuroblastoma according to its anatomical presence at diagnosis:[30][31][32]
* Stage 1: Localized tumor confined to the area of origin.
* Stage 2A: Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor.
* Stage 2B: Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor.
* Stage 3: Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement.
* Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S.
* Stage 4S: Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors).
Although international agreement on staging (INSS) has been used, the need for an international consensus on risk assignment has also been recognized in order to compare similar cohorts in results of studies. Beginning in 2005, representatives of the major pediatric oncology cooperative groups have met to review data for 8,800 people with neuroblastoma treated in Europe, Japan, USA, Canada, and Australia between 1990 and 2002. This task force has proposed the International Neuroblastoma Risk Group (INRG) classification system. Retrospective studies revealed the high survival rate of 12–18 month old age group, previously categorized as high-risk, and prompted the decision to reclassify 12–18 month old children without N-myc (also commonly referred to as MYCN) amplification to intermediate risk category.[33]
The new INRG risk assignment will classify neuroblastoma at diagnosis based on a new International Neuroblastoma Risk Group Staging System (INRGSS):
* Stage L1: Localized disease without image-defined risk factors.
* Stage L2: Localized disease with image-defined risk factors.
* Stage M: Metastatic disease.
* Stage MS: Metastatic disease "special" where MS is equivalent to stage 4S.
The new risk stratification will be based on the new INRGSS staging system, age (dichotomized at 18 months), tumor grade, N-myc amplification, unbalanced 11q aberration, and ploidy into four pre-treatment risk groups: very low, low, intermediate, and high risk.[4][34]
## Screening[edit]
Urine catecholamine level can be elevated in pre-clinical neuroblastoma. Screening asymptomatic infants at three weeks, six months, and one year has been performed in Japan, Canada, Austria and Germany since the 1980s.[35][36] Japan began screening six-month-olds for neuroblastoma via analysis of the levels of homovanillic acid and vanilmandelic acid in 1984. Screening was halted in 2004 after studies in Canada and Germany showed no reduction in deaths due to neuroblastoma, but rather caused an increase in diagnoses that would have disappeared without treatment, subjecting those infants to unnecessary surgery and chemotherapy.[37][38][39]
## Treatment[edit]
When the lesion is localized, it is generally curable. However, long-term survival for children with advanced disease older than 18 months of age is poor despite aggressive multimodal therapy (intensive chemotherapy, surgery, radiation therapy, stem cell transplant, differentiation agent isotretinoin also called 13-cis-retinoic acid, and frequently immunotherapy[40] with anti-GD2 monoclonal antibody therapy).
Biologic and genetic characteristics have been identified, which, when added to classic clinical staging, has allowed assignment to risk groups for planning treatment intensity.[41] These criteria include the age of the person, extent of disease spread, microscopic appearance, and genetic features including DNA ploidy and N-myc oncogene amplification (N-myc regulates microRNAs[42]), into low, intermediate, and high risk disease. A recent biology study (COG ANBL00B1) analyzed 2687 people with neuroblastoma and the spectrum of risk assignment was determined: 37% of neuroblastoma cases are low risk, 18% are intermediate risk, and 45% are high risk.[43] (There is some evidence that the high- and low-risk types are caused by different mechanisms, and are not merely two different degrees of expression of the same mechanism.)[44]
The therapies for these different risk categories are very different.
* Low-risk disease can frequently be observed without any treatment at all or cured with surgery alone.[45]
* Intermediate-risk disease is treated with surgery and chemotherapy.[46]
* High-risk neuroblastoma is treated with intensive chemotherapy, surgery, radiation therapy, bone marrow / hematopoietic stem cell transplantation,[47] biological-based therapy with 13-cis-retinoic acid (isotretinoin or Accutane)[48] and antibody therapy usually administered with the cytokines GM-CSF and IL-2.[49] A meta analysis has found evidence that in children with high-risk neuroblastoma, treatment with myeloablative therapy improves event-free survival but may increase the risk of side effects such as kidney problems when compared to conventional chemotherapy.[50]
People with low and intermediate risk disease have an excellent prognosis with cure rates above 90% for low risk and 70–90% for intermediate risk. In contrast, therapy for high-risk neuroblastoma the past two decades[when?] resulted in cures only about 30% of the time.[51] The addition of antibody therapy has raised survival rates for high-risk disease significantly. In March 2009, an early analysis of a Children's Oncology Group (COG) study with 226 people that are high-risk showed that two years after stem cell transplant 66% of the group randomized to receive ch14.18 antibody with GM-CSF and IL-2 were alive and disease-free compared to only 46% in the group that did not receive the antibody. The randomization was stopped so all people enrolling on the trial would receive the antibody therapy.[52]
Chemotherapy agents used in combination have been found to be effective against neuroblastoma. Agents commonly used in induction and for stem cell transplant conditioning are platinum compounds (cisplatin, carboplatin), alkylating agents (cyclophosphamide, ifosfamide, melphalan), topoisomerase II inhibitor (etoposide), anthracycline antibiotics (doxorubicin) and vinca alkaloids (vincristine). Some newer regimens include topoisomerase I inhibitors (topotecan and irinotecan) in induction which have been found to be effective against recurrent disease.
In November 2020, naxitamab was approved for medical use in the United States in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) to treat people one year of age and older with high-risk neuroblastoma in bone or bone marrow whose tumor did not respond to or has come back after previous treatments and has shown a partial response, minor response, or stable disease to prior therapy.[53][54]
## Prognosis[edit]
By data from England, the overall 5-year survival rate of neuroblastoma is 67%.[55] Between 20% and 50% of high-risk cases do not respond adequately to induction high-dose chemotherapy and are progressive or refractory.[56][57] Relapse after completion of frontline therapy is also common. Further treatment is available in phase I and phase II clinical trials that test new agents and combinations of agents against neuroblastoma, but the outcome remains very poor for relapsed high-risk disease.[58]
Most long-term survivors alive today had low or intermediate risk disease and milder courses of treatment compared to high-risk disease. The majority of survivors have long-term effects from the treatment. Survivors of intermediate and high-risk treatment often experience hearing loss, growth reduction, thyroid function disorders, learning difficulties, and greater risk of secondary cancers affect survivors of high-risk disease.[59][60] An estimated two of three survivors of childhood cancer will ultimately develop at least one chronic and sometimes life-threatening health problem within 20 to 30 years after the cancer diagnosis.[61][62][63]
### Cytogenetic profiles[edit]
Based on a series of 493 neuroblastoma samples, it has been reported that overall genomic pattern, as tested by array-based karyotyping, is a predictor of outcome in neuroblastoma:[64]
* Tumors presenting exclusively with whole chromosome copy number changes were associated with excellent survival.
* Tumors presenting with any kind of segmental chromosome copy number changes were associated with a high risk of relapse.
* Within tumors showing segmental alterations, additional independent predictors of decreased overall survival were N-myc amplification, 1p and 11q deletions, and 1q gain.
Earlier publications categorized neuroblastomas into three major subtypes based on cytogenetic profiles:[65][66]
* Subtype 1: favorable neuroblastoma with near triploidy and a predominance of numerical gains and losses, mostly representing non-metastatic NB stages 1, 2 and 4S.
* Subtypes 2A and 2B: found in unfavorable widespread neuroblastoma, stages 3 and 4, with 11q loss and 17q gain without N-myc amplification (subtype 2A) or with N-myc amplification often together with 1p deletions and 17q gain (subtype 2B).
Virtual karyotyping can be performed on fresh or paraffin-embedded tumors to assess copy number at these loci. SNP array virtual karyotyping is preferred for tumor samples, including neuroblastomas, because they can detect copy neutral loss of heterozygosity (acquired uniparental disomy). Copy neutral LOH can be biologically equivalent to a deletion and has been detected at key loci in neuroblastoma.[67] ArrayCGH, FISH, or conventional cytogenetics cannot detect copy neutral LOH.
## Epidemiology[edit]
Incidences and prognoses of adrenal tumors,[68] with "neuronal tumor" at right.
Neuroblastoma comprises 6–10% of all childhood cancers, and 15% of cancer deaths in children. The annual mortality rate is 10 per million children in the 0- to 4-year-old age group, and 4 per million in the 4- to 9-year old age group.[69]
The highest number of cases is in the first year of life, and some cases are congenital. The age range is broad, including older children and adults,[70] but only 10% of cases occur in people older than 5 years of age.[23] A large European study reported less than 2% of over 4000 neuroblastoma cases were over 18 years old.[71]
## History[edit]
Rudolf Virchow: the first to describe an abdominal tumor in a child as a "glioma"
In 1864 German physician Rudolf Virchow was the first to describe an abdominal tumor in a child as a "glioma". The characteristics of tumors from the sympathetic nervous system and the adrenal medulla were then noted in 1891 by German pathologist Felix Marchand.[72][73] In 1901 the distinctive presentation of stage 4S in infants (liver but no bone metastases) was described by William Pepper. In 1910 James Homer Wright understood the tumor to originate from primitive neural cells, and named it neuroblastoma. He also noted the circular clumps of cells in bone marrow samples which are now termed "Homer Wright rosettes". Of note, "Homer-Wright" with a hyphen is grammatically incorrect, as the eponym refers to just Dr. Wright.[74]
## Society and culture[edit]
### Legislative efforts[edit]
U.S. Representative Chet Edwards of Waco, Texas, successfully introduced legislation to earmark $150 million toward a cure for neuroblastoma and other cancers. The measure was signed into law in July 2008 by U.S. President George W. Bush. Edwards was inspired in the endeavor by the illness and subsequent death of Erin Channing Buenger (1997–2009) of Bryan, daughter of one of his constituents, Walter L. Buenger, head of the history department at Texas A&M University.[75]
## Research[edit]
Microscopic view of a NB cell line (SH-SY5Y) used in preclinical research for testing new agents
### Preclinical models[edit]
Neuroblastoma patient derived tumor xenografts (PDXs) have been created by orthotopic implantation of tumor samples into immunodeficient mice.[76] PDX models have several advantages over conventional cancer cell lines (CCL)s.[77] Neuroblastoma PDXs retain the genetic hallmarks of their corresponding tumors and PDXs display infiltrative growth and metastasis to distant organs.[76] PDX models are more predictive of clinical outcome as compared to conventional cancer cell line xenografts.[78] Neuroblastoma PDXs might thus serve as clinically relevant models to identify effective compounds against neuroblastoma.[76]
### Treatments[edit]
Recent focus has been to reduce therapy for low and intermediate risk neuroblastoma while maintaining survival rates at 90%.[79] A study of 467 people that are at intermediate risk enrolled in A3961 from 1997 to 2005 confirmed the hypothesis that therapy could be successfully reduced for this risk group. Those with favorable characteristics (tumor grade and response) received four cycles of chemotherapy, and those with unfavorable characteristics received eight cycles, with three-year event free survival and overall survival stable at 90% for the entire cohort. Future plans are to intensify treatment for those people with aberration of 1p36 or 11q23 chromosomes as well as for those who lack early response to treatment.[80][81]
By contrast, focus the past 20 years or more has been to intensify treatment for high-risk neuroblastoma. Chemotherapy induction variations, timing of surgery, stem cell transplant regimens, various delivery schemes for radiation, and use of monoclonal antibodies and retinoids to treat minimal residual disease continue to be examined. Recent phase III clinical trials with randomization have been carried out to answer these questions to improve survival of high-risk disease:
### Refractory and relapsed neuroblastoma[edit]
Chemotherapy with topotecan and cyclophosphamide is frequently used in refractory setting and after relapse.[82]
A haploidentical stem cell transplant, that is, donor cells derived from parents, is being studied in those with refractory or relapsing neuroblastoma as stem cells from the person themselves is not useful.[83]
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48. ^ Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris RE, Ramsay NK, et al. (October 1999). "Treatment of high-risk neuroblastoma with intensive chemotherapy, radiotherapy, autologous bone marrow transplantation, and 13-cis-retinoic acid. Children's Cancer Group". The New England Journal of Medicine. 341 (16): 1165–73. doi:10.1056/NEJM199910143411601. PMID 10519894.
49. ^ Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. (September 2010). "Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma". The New England Journal of Medicine. 363 (14): 1324–34. doi:10.1056/NEJMoa0911123. PMC 3086629. PMID 20879881.
50. ^ Yalçin B, Kremer LC, van Dalen EC (October 2015). "High-dose chemotherapy and autologous haematopoietic stem cell rescue for children with high-risk neuroblastoma". The Cochrane Database of Systematic Reviews (10): CD006301. doi:10.1002/14651858.cd006301.pub4. PMID 26436598.
51. ^ "Neuroblastoma Treatment". National Cancer Institute. 1980-01-01. Archived from the original on 2008-10-02. Retrieved 2008-07-30.
52. ^ Yu AL, Gilman MF, Ozkaynak WB, London S, Kreissman HX, Chen KK, Matthay SL, Cohn JM, Maris JM, Sondel PM (2009). "A phase III randomized trial of the chimeric anti-GD2 antibody ch14.18 with GM-CSF and IL2 as immunotherapy following dose intensive chemotherapy for high-risk neuroblastoma: Childrens Oncology Group (COG) study ANBL0032". Journal of Clinical Oncology. 27 (15 Suppl): 10067z. Archived from the original on 2016-01-10. Retrieved 2015-09-10.
53. ^ "Drugs Trials Snapshot: Danyelza". U.S. Food and Drug Administration (FDA). 25 November 2020. Retrieved 25 December 2020. This article incorporates text from this source, which is in the public domain.
54. ^ "Drug Approval Package: Danyelza". U.S. Food and Drug Administration (FDA). 22 December 2020. Retrieved 25 December 2020.
55. ^ "Neuroblastoma overview". Children with Cancer UK. Retrieved 2020-07-01.
56. ^ Kushner BH, Kramer K, LaQuaglia MP, Modak S, Yataghene K, Cheung NK (December 2004). "Reduction from seven to five cycles of intensive induction chemotherapy in children with high-risk neuroblastoma". Journal of Clinical Oncology. 22 (24): 4888–92. doi:10.1200/JCO.2004.02.101. PMID 15611504.
57. ^ Kreissman SG, Villablanca JG, Diller L, London WB, Maris JM, Park JR, Reynolds CP, von Allmen D, Cohn SL, Matthay KK (2007). "Response and toxicity to a dose-intensive multi-agent chemotherapy induction regimen for high risk neuroblastoma (HR-NB): A Children's Oncology Group (COG A3973) study". Journal of Clinical Oncology. 25 (18 Suppl): 9505. doi:10.1200/jco.2007.25.18_suppl.9505. Archived from the original on 2016-01-10.
58. ^ Ceschel S, Casotto V, Valsecchi MG, Tamaro P, Jankovic M, Hanau G, et al. (October 2006). "Survival after relapse in children with solid tumors: a follow-up study from the Italian off-therapy registry". Pediatric Blood & Cancer. 47 (5): 560–6. doi:10.1002/pbc.20726. PMID 16395684.
59. ^ Gurney JG, Tersak JM, Ness KK, Landier W, Matthay KK, Schmidt ML (November 2007). "Hearing loss, quality of life, and academic problems in long-term neuroblastoma survivors: a report from the Children's Oncology Group". Pediatrics. 120 (5): e1229-36. doi:10.1542/peds.2007-0178. PMID 17974716. S2CID 10606999.
60. ^ Trahair TN, Vowels MR, Johnston K, Cohn RJ, Russell SJ, Neville KA, et al. (October 2007). "Long-term outcomes in children with high-risk neuroblastoma treated with autologous stem cell transplantation". Bone Marrow Transplantation. 40 (8): 741–6. doi:10.1038/sj.bmt.1705809. PMID 17724446.
61. ^ Mozes, Alan (February 21, 2007). "Childhood Cancer Survivors Face Increased Sarcoma Risk". HealthDay. Archived from the original on September 8, 2015.
62. ^ Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, et al. (October 2006). "Chronic health conditions in adult survivors of childhood cancer". The New England Journal of Medicine. 355 (15): 1572–82. doi:10.1056/NEJMsa060185. PMID 17035650.
63. ^ Laverdière C, Liu Q, Yasui Y, Nathan PC, Gurney JG, Stovall M, et al. (August 2009). "Long-term outcomes in survivors of neuroblastoma: a report from the Childhood Cancer Survivor Study". Journal of the National Cancer Institute. 101 (16): 1131–40. doi:10.1093/jnci/djp230. PMC 2728747. PMID 19648511.
64. ^ Janoueix-Lerosey I, Schleiermacher G, Michels E, Mosseri V, Ribeiro A, Lequin D, et al. (March 2009). "Overall genomic pattern is a predictor of outcome in neuroblastoma" (PDF). Journal of Clinical Oncology. 27 (7): 1026–33. doi:10.1200/JCO.2008.16.0630. PMID 19171713.
65. ^ Vandesompele J, Baudis M, De Preter K, Van Roy N, Ambros P, Bown N, et al. (April 2005). "Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma" (PDF). Journal of Clinical Oncology. 23 (10): 2280–99. doi:10.1200/JCO.2005.06.104. PMID 15800319.
66. ^ Michels E, Vandesompele J, Hoebeeck J, Menten B, De Preter K, Laureys G, et al. (2006). "Genome wide measurement of DNA copy number changes in neuroblastoma: dissecting amplicons and mapping losses, gains and breakpoints". Cytogenetic and Genome Research. 115 (3–4): 273–82. doi:10.1159/000095924. PMID 17124410. S2CID 14012430.
67. ^ Carén H, Erichsen J, Olsson L, Enerbäck C, Sjöberg RM, Abrahamsson J, et al. (July 2008). "High-resolution array copy number analyses for detection of deletion, gain, amplification and copy-neutral LOH in primary neuroblastoma tumors: four cases of homozygous deletions of the CDKN2A gene". BMC Genomics. 9: 353. doi:10.1186/1471-2164-9-353. PMC 2527340. PMID 18664255.
68. ^ Data and references for pie chart are located at file description page in Wikimedia Commons.
69. ^ Brodeur GM, Hogarty MD, Mosse YP, Maris JM (1997). "Neuroblastoma". In Pizzo PA, Poplack DG (eds.). Principles and Practice of Pediatric Oncology (6th ed.). pp. 886–922. ISBN 978-1-60547-682-7.
70. ^ Franks LM, Bollen A, Seeger RC, Stram DO, Matthay KK (May 1997). "Neuroblastoma in adults and adolescents: an indolent course with poor survival". Cancer. 79 (10): 2028–35. doi:10.1002/(SICI)1097-0142(19970515)79:10<2028::AID-CNCR26>3.0.CO;2-V. PMID 9149032.
71. ^ Ladenstein R, Pötschger U, Hartman O, Pearson AD, Klingebiel T, Castel V, et al. (June 2008). "28 years of high-dose therapy and SCT for neuroblastoma in Europe: lessons from more than 4000 procedures". Bone Marrow Transplantation. 41 Suppl 2 (Suppl 2): S118-27. doi:10.1038/bmt.2008.69. PMID 18545256.
72. ^ Berthold F, Simon T (2006). "Clinical Presentation". In Cheung NV, Cohn SL (eds.). Neuroblastoma. Springer. pp. 63–85. ISBN 978-3-540-26616-7.
73. ^ Beckwith JB, Perrin EV (December 1963). "In Situ Neuroblastomas: A Contribution to the Natural History of Neural Crest Tumors". The American Journal of Pathology. 43: 1089–104. PMC 1949785. PMID 14099453.
74. ^ Rothenberg AB, Berdon WE, D'Angio GJ, Yamashiro DJ, Cowles RA (February 2009). "Neuroblastoma-remembering the three physicians who described it a century ago: James Homer Wright, William Pepper, and Robert Hutchison". Pediatric Radiology. 39 (2): 155–60. doi:10.1007/s00247-008-1062-z. PMID 19034443. S2CID 19611725.
75. ^ "Erin Buenger had a zest for living life fully". The Bryan College Station Eagle. April 12, 2009. Archived from the original on June 11, 2011.
76. ^ a b c Braekeveldt N, Wigerup C, Gisselsson D, Mohlin S, Merselius M, Beckman S, et al. (March 2015). "Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours". International Journal of Cancer. 136 (5): E252-61. doi:10.1002/ijc.29217. PMC 4299502. PMID 25220031.
77. ^ Malaney P, Nicosia SV, Davé V (March 2014). "One mouse, one patient paradigm: New avatars of personalized cancer therapy". Cancer Letters. 344 (1): 1–12. doi:10.1016/j.canlet.2013.10.010. PMC 4092874. PMID 24157811.
78. ^ Tentler JJ, Tan AC, Weekes CD, Jimeno A, Leong S, Pitts TM, et al. (April 2012). "Patient-derived tumour xenografts as models for oncology drug development". Nature Reviews. Clinical Oncology. 9 (6): 338–50. doi:10.1038/nrclinonc.2012.61. PMC 3928688. PMID 22508028.
79. ^ "Neuroblastoma Committee—Current Focus of Research". Archived from the original on September 25, 2006. Retrieved 2008-01-13.
80. ^ Baker DL, Schmidt ML, Cohn SL, Maris JM, London WB, Buxton A, et al. (September 2010). "Outcome after reduced chemotherapy for intermediate-risk neuroblastoma". The New England Journal of Medicine. 363 (14): 1313–23. doi:10.1056/NEJMoa1001527. PMC 2993160. PMID 20879880. Archived from the original on 2013-01-13.
81. ^ Baker DL, Schmidt ML, Cohn SL, Maris JM, London WB, Buxton A, et al. (September 2010). "Outcome after reduced chemotherapy for intermediate-risk neuroblastoma". The New England Journal of Medicine. 363 (14): 1313–23. doi:10.1056/NEJMoa1001527. PMC 2993160. PMID 20879880.
82. ^ Morgenstern DA, Baruchel S, Irwin MS (July 2013). "Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy". Journal of Pediatric Hematology/Oncology. 35 (5): 337–47. doi:10.1097/MPH.0b013e318299d637. PMID 23703550. S2CID 5529288.
83. ^ Illhardt T, Toporski J, Feuchtinger T, Turkiewicz D, Teltschik HM, Ebinger M, et al. (May 2018). "Haploidentical Stem Cell Transplantation for Refractory/Relapsed Neuroblastoma". Biology of Blood and Marrow Transplantation. Elsevier BV. 24 (5): 1005–1012. doi:10.1016/j.bbmt.2017.12.805. PMID 29307718.
## External links[edit]
* Neuroblastoma at Curlie
Classification
D
* ICD-10: C74.9
* ICD-9-CM: 194.0
* ICD-O: M9500/3
* OMIM: 256700
* MeSH: D009447
* DiseasesDB: 8935
* SNOMED CT: 432328008
External resources
* MedlinePlus: 001408
* eMedicine: med/2836 ped/1570
* Orphanet: 635
* v
* t
* e
Tumours of the nervous system
Endocrine
Sellar:
* Craniopharyngioma
* Pituicytoma
Other:
* Pinealoma
CNS
Neuroepithelial
(brain tumors,
spinal tumors)
Glioma
Astrocyte
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* Nerve sheath tumor
* Cranial and paraspinal nerves
* Neurofibroma
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Other
* WHO classification of the tumors of the central nervous system
Note: Not all brain tumors are of nervous tissue, and not all nervous tissue tumors are in the brain (see brain metastasis).
* v
* t
* e
Tumours of endocrine glands
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* Pinealoma
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MEN
* 1
* 2A
* 2B
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Neuroblastoma | c0027819 | 3,681 | wikipedia | https://en.wikipedia.org/wiki/Neuroblastoma | 2021-01-18T18:56:45 | {"gard": ["7185"], "mesh": ["D009447"], "umls": ["C0027819"], "icd-9": ["194.0"], "orphanet": ["635"], "wikidata": ["Q938205"]} |
Pustular psoriasis is a rare form of psoriasis that is characterized by widespread pustules and reddish skin. This condition can occur alone or with plaque-type psoriasis. Most cases of pustular psoriasis are thought to be "multifactorial" or associated with the effects of multiple genes in combination with lifestyle and environmental factors. There are several triggers for this conditions including withdrawal from corticosteroids, exposure to various medications and/or infections. Some cases of the generalized form are caused by changes (mutations) in the IL36RN gene and are inherited in an autosomal recessive pattern. In severe cases, hospitalization may be required. Treatment aims to alleviate the associated symptoms and may include certain medications and/or phototherapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Pustular psoriasis | c0152081 | 3,682 | gard | https://rarediseases.info.nih.gov/diseases/12813/pustular-psoriasis | 2021-01-18T17:58:02 | {"synonyms": []} |
Asymmetry in the pigmentation of the irides probably occurs as an isolated phenomenon inherited as a dominant (Calhoun, 1919). Whether hereditary heterochromia iridis ever exists independent of Horner syndrome (143000), Waardenburg syndrome (193500), or the piebald trait (172800) is not clear. The melanocytes of the uveal trait constitute a branching pseudosyncytium richly innervated by sympathetic nerves. Pigmentation of the iris does not occur in the absence of this innervation. Sympathetic fibers leave the lateral horn of the gray matter of the first and second thoracic segments, pass out in the anterior roots, and join the lateral sympathetic chain via the white rami communicantes. They then proceed to the superior cervical ganglion and along the distribution of the carotid artery to the head. Congenital (or at least connatal) Horner syndrome with associated heterochromia iridis can be produced by birth injury to the lower roots of the brachial plexus (Klumpke palsy). Byrne and Clough (1992) discussed the occurrence of hypochromia iridis following acquired Horner syndrome in a 40-year-old man who had suffered brachial plexus trauma in a motorcycle accident 23 years earlier. Heterochromia iridis (singular) is the designation that the purist reserves for different pigmentation in sectors of 1 iris, whereas heterochromia iridum (plural) is the term used when the 2 irides are of different color.
Morrison et al. (2000) examined 75 children with iris colobomata (120200). In 13 (17.3%) patients, noticeable iris heterochromia was present. In patients with unilateral coloboma, the heterochromia was characterized by the darker iris being the one affected with coloboma. In cases of bilateral iris colobomata with clinical microphthalmos and reduced corneal diameter, the variation in iris color was inconsistent. A fundus coloboma was not always present. The authors postulated that the iris coloboma-iris heterochromia association may result from the abnormal closure of the embryonic fissure, resulting in irregular or excessive migration of neural crest cells into the iris stroma. In addition, the high frequency of iris heterochromia-iris coloboma with microphthalmia suggests that an increased density of pigmented cells within the iris stroma may be a contributing factor.
Eyes \- Asymmetry of iris pigmentation Inheritance \- Autosomal dominant ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| HETEROCHROMIA IRIDIS | c0423318 | 3,683 | omim | https://www.omim.org/entry/142500 | 2019-09-22T16:40:17 | {"mesh": ["C538115"], "omim": ["142500"]} |
This article is about the disease. For information about the medieval plague, see Black Death.
Human and animal disease
Bubonic plague
A bubo on the upper thigh of a person infected with bubonic plague
SpecialtyInfectious disease
SymptomsFever, headaches, vomiting, swollen lymph nodes[1][2]
Usual onset1–7 days after exposure[1]
CausesYersinia pestis spread by fleas[1]
Diagnostic methodFinding the bacterium in the blood, sputum, or lymph nodes[1]
TreatmentAntibiotics such as streptomycin, gentamicin, or doxycycline[3][4]
Frequency650 cases reported a year[1]
Deaths10% mortality with treatment[3]
30-90% if untreated[1][3]
Bubonic plague is one of three types of plague caused by the plague bacterium (Yersinia pestis).[1] One to seven days after exposure to the bacteria, flu-like symptoms develop.[1] These symptoms include fever, headaches, and vomiting.[1] Swollen and painful lymph nodes occur in the area closest to where the bacteria entered the skin.[2] Occasionally, the swollen lymph nodes, known as "buboes" pictured to the right, may break open.[1]
The three types of plague are the result of the route of infection: bubonic plague, septicemic plague, and pneumonic plague.[1] Bubonic plague is mainly spread by infected fleas from small animals.[1] It may also result from exposure to the body fluids from a dead plague-infected animal.[5] Mammals such as rabbits, hares, and some cat species are susceptible to bubonic plague, and typically die upon contraction.[6] In the bubonic form of plague, the bacteria enter through the skin through a flea bite and travel via the lymphatic vessels to a lymph node, causing it to swell.[1] Diagnosis is made by finding the bacteria in the blood, sputum, or fluid from lymph nodes.[1]
Prevention is through public health measures such as not handling dead animals in areas where plague is common.[7] [1] Vaccines have not been found to be very useful for plague prevention.[1] Several antibiotics are effective for treatment, including streptomycin, gentamicin, and doxycycline.[3][4] Without treatment, plague results in the death of 30% to 90% of those infected.[1][3] Death, if it occurs, is typically within 10 days.[8] With treatment, the risk of death is around 10%.[3] Globally between 2010 and 2015 there were 3,248 documented cases, which resulted in 584 deaths.[1] The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.[1]
The plague was the cause of the Black Death that swept through Asia, Europe, and Africa in the 14th century and killed an estimated 50 million people.[1][9] This was about 25% to 60% of the European population.[1][10] Because the plague killed so many of the working population, wages rose due to the demand for labor.[10] Some historians see this as a turning point in European economic development.[10] The disease was also responsible for the Plague of Justinian, originating in the Eastern Roman Empire in the 6th century CE, as well as the third epidemic, affecting China, Mongolia, and India, originating in the Yunnan Province in 1855.[11] The term bubonic is derived from the Greek word βουβών, meaning "groin".[12]
## Contents
* 1 Cause
* 2 Signs and symptoms
* 3 Diagnosis
* 4 Prevention
* 5 Treatment
* 6 Epidemiology
* 7 History
* 7.1 First pandemic
* 7.2 Second pandemic
* 7.3 Third pandemic
* 8 Society and culture
* 8.1 Biological warfare
* 8.2 Continued research
* 9 See also
* 10 References
* 11 Further reading
* 12 External links
## Cause
An Oriental rat flea (Xenopsylla cheopis) infected with the plague bacterium (Yersinia pestis), which appears as a dark mass in the gut. The foregut of this flea is blocked by a Y. pestis biofilm; when the flea attempts to feed on an uninfected host, Y. pestis from the foregut is regurgitated into the wound, causing infection.
Bubonic plague is an infection of the lymphatic system, usually resulting from the bite of an infected flea, Xenopsylla cheopis (the Oriental rat flea).[13] Several flea species carried the bubonic plague, such as Pulex irritans (the human flea), Xenopsylla cheopis, and Ceratophyllus fasciatus.[13] Xenopsylla cheopis was the most effective flea species for transmittal.[13] In very rare circumstances, as in septicemic plague, the disease can be transmitted by direct contact with infected tissue or exposure to the cough of another human. The flea is parasitic on house and field rats, and seeks out other prey when its rodent hosts die. The bacteria remain harmless to the flea, allowing the new host to spread the bacteria. Rats were an amplifying factor to bubonic plague due to their common association with humans as well as the nature of their blood.[14] The rat's blood allowed the rat to withstand a major concentration of the plague.[14] The bacteria form aggregates in the gut of infected fleas and this results in the flea regurgitating ingested blood, which is now infected, into the bite site of a rodent or human host. Once established, bacteria rapidly spread to the lymph nodes and multiply. The fleas that transmit the disease only directly infect humans when the rat population in the area is wiped out from a mass infection.[15] Furthermore, in areas of a large population of rats, the animals are able to harbor low levels of the plague infection without causing human outbreaks. [14] With no new rat inputs being added to the population from other areas, the infection would only spread to humans in very rare cases of overcrowding.[14]
## Signs and symptoms
Necrosis of the nose, the lips, and the fingers and residual bruising over both forearms in a person recovering from bubonic plague that disseminated to the blood and the lungs. At one time, the person's entire body was bruised.
After being transmitted via the bite of an infected flea, the Y. pestis bacteria become localized in an inflamed lymph node, where they begin to colonize and reproduce. Infected lymph nodes develop hemorrhages, which result in death of tissue.[16]Y. pestis bacilli can resist phagocytosis and even reproduce inside phagocytes and kill them. As the disease progresses, the lymph nodes can hemorrhage and become swollen and necrotic. Bubonic plague can progress to lethal septicemic plague in some cases. The plague is also known to spread to the lungs and become the disease known as the pneumonic plague. Symptoms appear 2–7 days after getting bit and they include:[13]
* Chills
* General ill feeling (malaise)
* High fever >39 °C (102.2 °F)
* Muscle cramps[16]
* Seizures
* Smooth, painful lymph gland swelling called a bubo, commonly found in the groin, but may occur in the armpits or neck, most often near the site of the initial infection (bite or scratch)
* Pain may occur in the area before the swelling appears
* Gangrene of the extremities such as toes, fingers, lips, and tip of the nose.[17]
* Buboes
The best-known symptom of bubonic plague is one or more infected, enlarged, and painful lymph nodes, known as buboes. Buboes associated with the bubonic plague are commonly found in the armpits, upper femoral, groin and neck region. symptoms include heavy breathing, continuous vomiting of blood (hematemesis), aching limbs, coughing, and extreme pain caused by the decay or decomposition of the skin while the person is still alive. Additional symptoms include extreme fatigue, gastrointestinal problems, spleen inflammation, lenticulae (black dots scattered throughout the body), delirium, coma, organ failure, and death.[18] Organ failure is a result of the bacteria infecting organs through the blood stream.[13] Other forms of the disease include septicemic plague and pneumonic plague in which the bacterium reproduces in the person's blood and lungs respectively[citation needed]
## Diagnosis
Laboratory testing is required in order to diagnose and confirm plague. Ideally, confirmation is through the identification of Y. pestis culture from a patient sample. Confirmation of infection can be done by examining serum taken during the early and late stages of infection. To quickly screen for the Y. pestis antigen in patients, rapid dipstick tests have been developed for field use.[19]
Gram-Negative Yersinia pestis bacteria. The culture was grown over a 72 hour time period
Samples taken for testing include:[20]
* Buboes: Swollen lymph nodes (buboes) characteristic of bubonic plague, a fluid sample can be taken from them with a needle.
* Blood
* Lungs
## Prevention
Bubonic plague outbreaks are controlled by pest control and modern sanitation techniques. This disease uses fleas commonly found on rats as a vector to jump from animals to humans. The mortality rate hits its peak during the hot and humid months of June, July and August.[21] Furthermore, the plague most effected those of poor upbringing due to greater exposure, poor sanitation techniques and lack of a heathy immune system due to a poor diet.[21] The successful control of rat populations in dense urban areas is essential to outbreak prevention. One example is the use of Sulfurozador, a fumigation chemical used to eradicate the pest that spread the bubonic plague, in Buenos Aires, Argentina during the early 18th century.[22] Targeted chemoprophylaxis, sanitation, and vector control also played a role in controlling the 2003 Oran outbreak of the bubonic plague.[23] Another mean of prevention in large European cities was a city-wide quarantine to not only limit interaction with people that were infected, but also to limit the interaction with the infected rats.[24]
## Treatment
Several classes of antibiotics are effective in treating bubonic plague. These include aminoglycosides such as streptomycin and gentamicin, tetracyclines (especially doxycycline), and the fluoroquinolone ciprofloxacin. Mortality associated with treated cases of bubonic plague is about 1–15%, compared to a mortality of 40–60% in untreated cases.[25]
People potentially infected with the plague need immediate treatment and should be given antibiotics within 24 hours of the first symptoms to prevent death. Other treatments include oxygen, intravenous fluids, and respiratory support. People who have had contact with anyone infected by pneumonic plague are given prophylactic antibiotics.[26] Using the broad-based antibiotic streptomycin has proven to be dramatically successful against the bubonic plague within 12 hours of infection.[27]
## Epidemiology
Main article: Epidemiology of plague
Distribution of plague-infected animals, 1998
Globally between 2010 and 2015 there were 3,248 documented cases, which resulted in 584 deaths.[1] The countries with the greatest number of cases are the Democratic Republic of the Congo, Madagascar, and Peru.[1]
For over a decade since 2001, Zambia, India, Malawi, Algeria, China, Peru, and the Democratic Republic of the Congo had the most plague cases with over 1,100 cases in the Democratic Republic of the Congo alone. From 1,000 to 2,000 cases are conservatively reported per year to the WHO.[28] From 2012 to 2017, reflecting political unrest and poor hygienic conditions, Madagascar began to host regular epidemics.[28]
Between 1900 and 2015, the United States had 1,036 human plague cases with an average of 9 cases per year. In 2015, 16 people in the Western United States developed plague, including 2 cases in Yosemite National Park.[29] These US cases usually occur in rural northern New Mexico, northern Arizona, southern Colorado, California, southern Oregon, and far western Nevada.[30]
In November 2017, the Madagascar Ministry of Health reported an outbreak to WHO (World Health Organization) with more cases and deaths than any recent outbreak in the country. Unusually, most of the cases were pneumonic rather than bubonic.[31]
In June 2018, a child was confirmed to be the first person in Idaho to be infected by bubonic plague in nearly 30 years.[32]
A couple died in May 2019, in Mongolia, while hunting marmots.[33] Another two people in the province of Inner Mongolia, China were treated in November 2019 for the disease.[34]
Spread of the Bubonic Plague Through Time in Europe (2nd Pandemic)
In July 2020, in Bayannur, Inner Mongolia of China, a human case of bubonic plague was reported. Officials responded by activating a city-wide plague-prevention system for the remainder of the year.[35] Also in July 2020, in Mongolia, a teenager died from bubonic plague after consuming infected marmot meat.[36]
## History
Yersinia pestis has been discovered in archaeological finds from the Late Bronze Age (~3800 BP).[37] The bacteria is identified by ancient DNA in human teeth from Asia and Europe dating from 2,800 to 5,000 years ago. [38]
### First pandemic
Main article: Plague of Justinian
The first recorded epidemic affected the Sassanian Empire and their arch-rivals, the Eastern Roman Empire (Byzantine Empire) and was named the Plague of Justinian after emperor Justinian I, who was infected but survived through extensive treatment.[39][40] The pandemic resulted in the deaths of an estimated 25 million (6th century outbreak) to 50 million people (two centuries of recurrence).[41][42] The historian Procopius wrote, in Volume II of History of the Wars, of his personal encounter with the plague and the effect it had on the rising empire. In the spring of 542, the plague arrived in Constantinople, working its way from port city to port city and spreading around the Mediterranean Sea, later migrating inland eastward into Asia Minor and west into Greece and Italy. The Plague of Justinian is said to have been "completed" in the middle of the 8th century.[14] Because the infectious disease spread inland by the transferring of merchandise through Justinian's efforts in acquiring luxurious goods of the time and exporting supplies, his capital became the leading exporter of the bubonic plague. Procopius, in his work Secret History, declared that Justinian was a demon of an emperor who either created the plague himself or was being punished for his sinfulness.[42]
### Second pandemic
Main articles: Black Death and Second plague pandemic
Citizens of Tournai bury plague victims. Miniature from The Chronicles of Gilles Li Muisis (1272–1352). Bibliothèque royale de Belgique, MS 13076-77, f. 24v.
People who died of bubonic plague in a mass grave from 1720 to 1721 in Martigues, France
In the Late Middle Ages Europe experienced the deadliest disease outbreak in history when the Black Death, the infamous pandemic of bubonic plague, hit in 1347, killing one-third of the European human population. Some historians believe that society subsequently became more violent as the mass mortality rate cheapened life and thus increased warfare, crime, popular revolt, waves of flagellants, and persecution.[43] The Black Death originated in Central Asia and spread from Italy and then throughout other European countries. Arab historians Ibn Al-Wardni and Almaqrizi believed the Black Death originated in Mongolia. Chinese records also showed a huge outbreak in Mongolia in the early 1330s.[44] Research published in 2002 suggests that it began in early 1346 in the steppe region, where a plague reservoir stretches from the northwestern shore of the Caspian Sea into southern Russia. The Mongols had cut off the trade route, the Silk Road, between China and Europe which halted the spread of the Black Death from eastern Russia to Western Europe. The epidemic began with an attack that Mongols launched on the Italian merchants' last trading station in the region, Caffa in the Crimea.[27] In late 1346, plague broke out among the besiegers and from them penetrated into the town. The Mongol forces catapulted plague infected corpses into Caffa as a form of attack, one of the first known instances of biological warfare.[45] When spring arrived, the Italian merchants fled on their ships, unknowingly carrying the Black Death. Carried by the fleas on rats, the plague initially spread to humans near the Black Sea and then outwards to the rest of Europe as a result of people fleeing from one area to another. Rats migrated with humans, traveling among grain bags, clothing, ships, wagons, and grain husks.[18] Continued research indicates that black rats, those that primarily transmitted the disease, prefer grain as a primary meal.[14] Due to this, the major bulk grain fleets that transported major city's food shipments from Africa and Alexandria to the heavily populated areas, and then unloaded by hand, played a role in the transmission effectiveness of the plague.[14]
### Third pandemic
Main article: Third plague pandemic
The plague resurfaced for a third time in the mid-19th century. Like the two previous outbreaks, this one also originated in Eastern Asia, most likely in Yunnan, a province of China, where there are several natural plague foci.[46] The initial outbreaks occurred in the second half of the 18th century.[47][48] The disease remained localized in Southwest China for several years before spreading. In the city of Canton, beginning in January 1894, the disease killed 80,000 people by June. Daily water-traffic with the nearby city of Hong Kong rapidly spread the plague there, killing over 2,400 within two months during the 1894 Hong Kong plague.[49]
Also known as the modern pandemic, the third pandemic spread the disease to port cities throughout the world in the second half of the 19th century and the early 20th century via shipping routes.[50] The plague infected people in Chinatown in San Francisco from 1900 to 1904,[51] and in the nearby locales of Oakland and the East Bay again from 1907 to 1909.[52] During the outbreak from 1900 to 1904 in San Francisco is when authorities made permanent the Chinese Exclusion Act. This law was originally signed into existence by President Chester A. Arthur in 1882. The Chinese Exclusion Act was supposed to last for 10 years, but was renewed in 1892 with the Geary Act and subsequently made permanent in 1902 during the outbreak of plague in Chinatown, San Francisco. The last major outbreak in the United States occurred in Los Angeles in 1924,[53] though the disease is still present in wild rodents, and can be passed to humans that come in contact with them.[54] According to the World Health Organization, the pandemic was considered active until 1959, when worldwide casualties dropped to 200 per year. In 1994, a plague outbreak in five Indian states caused an estimated 700 infections (including 52 deaths) and triggered a large migration of Indians within India as they tried to avoid the plague.[citation needed]
## Society and culture
See also: Black Death in medieval culture
Contemporary engraving of Marseille during the Great Plague in 1720
The scale of death and social upheaval associated with plague outbreaks has made the topic prominent in a number of historical and fictional accounts since the disease was first recognized. The Black Death in particular is described and referenced in numerous contemporary sources, some of which, including works by Chaucer, Boccaccio, and Petrarch, are considered part of the Western canon. The Decameron, by Boccaccio, is notable for its use of a frame story involving individuals who have fled Florence for a secluded villa to escape the Black Death. First-person, sometimes sensationalized or fictionalized, accounts of living through plague years have also been popular across centuries and cultures. For example, Samuel Pepys's diary makes a number of references to his first-hand experiences of the Great Plague of London in 1665–6.[55]
Later works, such as Albert Camus's novel The Plague or Ingmar Bergman's film The Seventh Seal have used bubonic plague in settings, such as quarantined cities in either medieval or modern times, as a backdrop to explore a variety of concepts. Common themes include the breakdown of society, institutions, and individuals during the plague, the cultural and psychological existential confrontation with mortality, and the allegorical use of the plague in reference to contemporary moral or spiritual questions.[citation needed]
### Biological warfare
Some of the earliest instances of biological warfare were said to have been products of the plague, as armies of the 14th century were recorded catapulting diseased corpses over the walls of towns and villages to spread the pestilence. This was done by Jani Beg when he attacked the city of Kaffa in 1343.[citation needed]
Later, plague was used during the Second Sino-Japanese War as a bacteriological weapon by the Imperial Japanese Army. These weapons were provided by Shirō Ishii's units and used in experiments on humans before being used on the field. For example, in 1940, the Imperial Japanese Army Air Service bombed Ningbo with fleas carrying the bubonic plague.[56] During the Khabarovsk War Crime Trials, the accused, such as Major General Kiyoshi Kawashima, testified that, in 1941, 40 members of Unit 731 air-dropped plague-contaminated fleas on Changde. These operations caused epidemic plague outbreaks.[24]
### Continued research
Substantial research has been done regarding the origin of the plague and how it traveled through the continent. [14] Mitochondrial DNA of modern rats in Western Europe indicated that these rats came from two different area one being Africa and the other being unclear of a specific origin.[14] The research regarding this pandemic has greatly increased with technology. [14] Through archaeo-molecular investigation, researchers have discovered DNA of plague bacillus in the dental core of those that fell ill to the plague.[14] Analysis of teeth of the deceased allows researchers to further understand both the demographics and mortuary patterns of the is disease. For example in 2013, archeologist uncovered and burial mound to reveal 17 bodies, mainly children, who had died of the Bubonic plaque. The anglicized these burial remains using radio dating to determine they were from the 1530's and dental core analysis revealed the presence of Yersinia Pestis.[57] Other evidence for rats that is currently still being researched consists of gnaw marks on bones, predator pellets and rat remains that were preserved in situ.[14] This research allows individuals to trace early rat remains to track the path traveled and in turn connect the impact of the Bubonic Plague to specific breeds of rats.[14] Burial sites, known as plague pits, offer archaeologists an opportunity to studying the remains of people who died from the plague.[58]
Another research study indicates that these separate pandemics were all interconnected.[15] A current computer model indicates that the disease did not go away in between these pandemics.[15] It rather lurked within the rat population for years without causing human epidemics.[15] This, in turn, combated those that recommended killing the rats in heavily populated cities in an effort to combat the plague. [15] This would be an ineffective strategy, because cutting out the rats from the scenario means that many infected fleas will be released to attach to human hosts. [15]
## See also
* List of cutaneous conditions
* List of epidemics
* Miasma theory
* Plague (disease)
* Plague doctor
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## Further reading
Wikisource has original text related to this article:
An Account of the Plague at Constantinople
* Alexander JT (2003) [First published 1980]. Bubonic Plague in Early Modern Russia: Public Health and Urban Disaster. Oxford, UK; New York, NY: Oxford University Press. ISBN 978-0-19-515818-2. OCLC 50253204.
* Carol B (1996). Bubonic Plague in Nineteenth-Century China. Stanford, CA: Stanford University Press. ISBN 978-0-8047-2661-0. OCLC 34191853.
* Biddle W (2002). A Field Guide to Germs (2nd Anchor Books ed.). New York: Anchor Books. ISBN 978-1-4000-3051-4. OCLC 50154403.
* Little LK (2007). Plague and the End of Antiquity: The Pandemic of 541–750. New York, NY: Cambridge University Press. ISBN 978-0-521-84639-4. OCLC 65361042.
* Rosen W (2007). Justinian's Flea: Plague, Empire and the Birth of Europe. London, England: Viking Penguin. ISBN 978-0-670-03855-8.
* Scott S, Duncan CJ (2001). Biology of Plagues: Evidence from Historical Populations. Cambridge, UK; New York, NY: Cambridge University Press. ISBN 978-0-521-80150-8. OCLC 44811929.
* Batten-Hill D (2011). This Son of York. Kendal, England: David Batten-Hill. ISBN 978-1-78176-094-9. Archived from the original on 20 May 2013. Retrieved 27 August 2018.
* Kool JL (April 2005). "Risk of person-to-person transmission of pneumonic plague". Clinical Infectious Diseases. 40 (8): 1166–72. doi:10.1086/428617. PMID 15791518.
## External links
Classification
D
* ICD-10: A20.0
* ICD-9-CM: 020.0
* DiseasesDB: 14226
External resources
* MedlinePlus: 000596
* v
* t
* e
Proteobacteria-associated Gram-negative bacterial infections
α
Rickettsiales
Rickettsiaceae/
(Rickettsioses)
Typhus
* Rickettsia typhi
* Murine typhus
* Rickettsia prowazekii
* Epidemic typhus, Brill–Zinsser disease, Flying squirrel typhus
Spotted
fever
Tick-borne
* Rickettsia rickettsii
* Rocky Mountain spotted fever
* Rickettsia conorii
* Boutonneuse fever
* Rickettsia japonica
* Japanese spotted fever
* Rickettsia sibirica
* North Asian tick typhus
* Rickettsia australis
* Queensland tick typhus
* Rickettsia honei
* Flinders Island spotted fever
* Rickettsia africae
* African tick bite fever
* Rickettsia parkeri
* American tick bite fever
* Rickettsia aeschlimannii
* Rickettsia aeschlimannii infection
Mite-borne
* Rickettsia akari
* Rickettsialpox
* Orientia tsutsugamushi
* Scrub typhus
Flea-borne
* Rickettsia felis
* Flea-borne spotted fever
Anaplasmataceae
* Ehrlichiosis: Anaplasma phagocytophilum
* Human granulocytic anaplasmosis, Anaplasmosis
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Rhizobiales
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* Brucella abortus
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Bartonellaceae
* Bartonellosis: Bartonella henselae
* Cat-scratch disease
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* Bacillary angiomatosis
* Bartonella bacilliformis
* Carrion's disease, Verruga peruana
β
Neisseriales
M+
* Neisseria meningitidis/meningococcus
* Meningococcal disease, Waterhouse–Friderichsen syndrome, Meningococcal septicaemia
M−
* Neisseria gonorrhoeae/gonococcus
* Gonorrhea
ungrouped:
* Eikenella corrodens/Kingella kingae
* HACEK
* Chromobacterium violaceum
* Chromobacteriosis infection
Burkholderiales
* Burkholderia pseudomallei
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* Bordetella pertussis/Bordetella parapertussis
* Pertussis
γ
Enterobacteriales
(OX−)
Lac+
* Klebsiella pneumoniae
* Rhinoscleroma, Pneumonia
* Klebsiella granulomatis
* Granuloma inguinale
* Klebsiella oxytoca
* Escherichia coli: Enterotoxigenic
* Enteroinvasive
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Slow/weak
* Serratia marcescens
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* Citrobacter koseri/Citrobacter freundii
Lac−
H2S+
* Salmonella enterica
* Typhoid fever, Paratyphoid fever, Salmonellosis
H2S−
* Shigella dysenteriae/sonnei/flexneri/boydii
* Shigellosis, Bacillary dysentery
* Proteus mirabilis/Proteus vulgaris
* Yersinia pestis
* Plague/Bubonic plague
* Yersinia enterocolitica
* Yersiniosis
* Yersinia pseudotuberculosis
* Far East scarlet-like fever
Pasteurellales
Haemophilus:
* H. influenzae
* Haemophilus meningitis
* Brazilian purpuric fever
* H. ducreyi
* Chancroid
* H. parainfluenzae
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Pasteurella multocida
* Pasteurellosis
* Actinobacillus
* Actinobacillosis
Aggregatibacter actinomycetemcomitans
* HACEK
Legionellales
* Legionella pneumophila/Legionella longbeachae
* Legionnaires' disease
* Coxiella burnetii
* Q fever
Thiotrichales
* Francisella tularensis
* Tularemia
Vibrionaceae
* Vibrio cholerae
* Cholera
* Vibrio vulnificus
* Vibrio parahaemolyticus
* Vibrio alginolyticus
* Plesiomonas shigelloides
Pseudomonadales
* Pseudomonas aeruginosa
* Pseudomonas infection
* Moraxella catarrhalis
* Acinetobacter baumannii
Xanthomonadaceae
* Stenotrophomonas maltophilia
Cardiobacteriaceae
* Cardiobacterium hominis
* HACEK
Aeromonadales
* Aeromonas hydrophila/Aeromonas veronii
* Aeromonas infection
ε
Campylobacterales
* Campylobacter jejuni
* Campylobacteriosis, Guillain–Barré syndrome
* Helicobacter pylori
* Peptic ulcer, MALT lymphoma, Gastric cancer
* Helicobacter cinaedi
* Helicobacter cellulitis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Bubonic plague | c0282312 | 3,684 | wikipedia | https://en.wikipedia.org/wiki/Bubonic_plague | 2021-01-18T18:35:00 | {"gard": ["183"], "mesh": ["D010930"], "umls": ["C0282312"], "icd-10": ["020.0"], "wikidata": ["Q217519"]} |
Chromosome 4q deletion is a chromosome abnormality that affects many different parts of the body. People with this condition are missing genetic material located on the long arm (q) of chromosome 4 in each cell. The severity of the condition and the associated signs and symptoms vary based on the size and location of the deletion and which genes are involved. Common features shared by many people with this deletion include distinctive craniofacial features, skeletal abnormalities, heart defects, intellectual disability, developmental delay, and short stature. Most cases are not inherited, although affected people can pass the deletion on to their children. Treatment is based on the signs and symptoms present in each person.
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Chromosome 4q deletion | c0265404 | 3,685 | gard | https://rarediseases.info.nih.gov/diseases/1340/chromosome-4q-deletion | 2021-01-18T18:01:21 | {"mesh": ["C537639"], "synonyms": ["Deletion 4q", "Monosomy 4q", "4q deletion", "4q monosomy", "Partial monosomy 4q"]} |
Ectoparasitic infestation
SpecialtyInfectious disease
An ectoparasitic infestation is a parasitic disease caused by organisms that live primarily on the surface of the host.
Examples:
* Scabies
* Crab louse (pubic lice)
* Pediculosis (head lice)[1]
* Lernaeocera branchialis (cod worm)
## See also[edit]
* Ectoparasiticide
## References[edit]
1. ^ Estrada B (January 2003). "Ectoparasitic infestations in homeless children". Semin Pediatr Infect Dis. 14 (1): 20–4. doi:10.1053/spid.2003.127213. PMID 12748918.
## External links[edit]
Classification
D
* ICD-10: B85-B89
* ICD-9-CM: 132-134
* MeSH: D004478
* v
* t
* e
Arthropods and ectoparasite-borne diseases and infestations
Insecta
Louse
* Body louse (pediculosis corporis) / Head louse (head lice infestation)
* Crab louse (phthiriasis)
Hemiptera
* Bed bug (cimicosis)
Fly
* Dermatobia hominis / Cordylobia anthropophaga / Cochliomyia hominivorax (myiasis)
* Mosquito (mosquito-borne disease)
Flea
* Tunga penetrans (tungiasis)
Crustacea
Pentastomida
* Linguatula serrata (linguatulosis)
* Porocephalus crotali / Armillifer armillatus (porocephaliasis)
* For ticks and mites, see Template:Tick and mite-borne diseases and infestations
This infectious disease article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Ectoparasitic infestation | c0013578 | 3,686 | wikipedia | https://en.wikipedia.org/wiki/Ectoparasitic_infestation | 2021-01-18T18:57:44 | {"mesh": ["D004478"], "umls": ["C0013578"], "icd-9": ["134", "132"], "icd-10": ["B89", "B85"], "wikidata": ["Q5334259"]} |
PACS1 syndrome is a condition in which all affected individuals have intellectual disability, speech and language problems, and a distinct facial appearance. Many affected individuals have additional neurological, behavioral, and health problems.
In PACS1 syndrome, intellectual disability typically ranges from mild to moderate. Individuals with this condition also have problems with producing speech (expressive language). Speech development ranges from limited language to few words or no speech.
Individuals with PACS1 syndrome have a distinct facial appearance. Facial features include thick and highly arched eyebrows, long eyelashes, widely set eyes (hypertelorism), outside corners of the eyes that point downward (downslanting palpebral fissures), droopy eyelids (ptosis), a rounded nasal tip, a wide mouth with corners that point downward, a thin upper lip, a smooth area between the nose and upper lip (philtrum), widely spaced teeth, and ears that are low-set with fewer folds and grooves than normal (described as "simple"). Abnormalities of other body systems can also occur, such as malformations of the heart, brain, eyes, or other organs. Males may have undescended testes (cryptorchidism).
Children with PACS1 syndrome often have problems learning to eat solid food and prefer soft foods. When given solid foods, affected children often swallow without chewing. These food issues tend to persist throughout life. Some affected individuals experience a backflow of stomach acids into the esophagus (gastroesophageal reflux).
Additional neurological problems can occur in PACS1 syndrome. Some affected individuals have features of autism spectrum disorder, which is characterized by impaired communication and social interaction. Attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), self-injury, or frustration leading to tantrums can also occur. Most individuals with PACS1 syndrome have seizures that vary in type and age of onset. Some people with PACS1 syndrome have weak muscle tone (hypotonia). Individuals with this condition are often delayed in walking, with some developing an unsteady walking style (gait). Rarely, affected individuals have frequent falls and gradually lose their ability to walk in late childhood, requiring wheelchair assistance.
## Frequency
The prevalence of PACS1 syndrome is unknown; more than 30 affected individuals have been described in the scientific literature.
## Causes
PACS1 syndrome is caused by mutations in a gene called PACS1. This gene provides instructions for making a protein that helps transport molecules and other proteins to cells and tissues where they are needed. The PACS1 protein is found in a complex network of membranes known as the trans-Golgi network, which sorts proteins and other molecules and sends them to their intended destinations inside or outside the cell. The PACS1 protein is most active during development before birth.
Almost all cases of PACS1 syndrome are caused by the same mutation. This and other PACS1 gene mutations are thought to impair the protein's ability to aid in the transport of certain molecules and proteins. Such an impairment likely results in the accumulation or misplacement of molecules or proteins within cells; however, the effects of these accumulated substances is unclear. Research suggests that impaired PACS1 protein function disrupts normal development of structures in the face, leading to a distinct facial appearance. It is likely that the development of other body systems are similarly affected by impaired PACS1 protein function, leading to other signs and symptoms of PACS1 syndrome, but more research is needed to understand the mechanisms.
### Learn more about the gene associated with PACS1 syndrome
* PACS1
## Inheritance Pattern
This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Most cases of this condition result from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual’s parent or in early embryonic development. These cases occur in people with no history of the disorder in their family.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| PACS1 syndrome | c3554343 | 3,687 | medlineplus | https://medlineplus.gov/genetics/condition/pacs1-syndrome/ | 2021-01-27T08:25:02 | {"gard": ["13043"], "omim": ["615009"], "synonyms": []} |
A rare organic aciduria, due to deficiency of 3-hydroxy-3-methylglutaryl-CoA lyase characterized by episodes of metabolic decompensation with hypoketotic hypoglycemia triggered by periods of fasting or infections.
## Epidemiology
3-hydroxy-3-methylglutaric aciduria (3HMG) occurs in all ethnic groups. The conditions is extremely rare in the United States, Taiwan and mainland China where incidence is estimated at less than 1/1,000,000; however, it is more frequently observed in Saudi Arabia, Portugal and Spain. In Portugal, the birth prevalence is estimated at 1/125,000 live births.
## Clinical description
The clinical presentation is heterogeneous, ranging from severe neonatal onset with potentially fatal outcome to presentation in adulthood. Most patients became symptomatic within the first year of life (50% in neonatal period) with episodes of metabolic decompensation triggered by periods of fasting or infections, which when left untreated may lead to neurological sequelae. Newborns or infants present with acidosis and hypoglycemia, accompanied by vomiting, dehydration, hypotonia and lethargy. Acute decompensation is triggered by infections, vaccinations, and dietary changes. The typical laboratory findings include hypoglycemia, acidosis, an increased anion gap, hyperammonemia and elevated transaminases. Long-term neurological complications are common. Half of the patients have a normal cognitive development while the remainder shows psychomotor deficits. Speech and motor developmental delay are frequent. Cerebral MRI frequently reveals diffuse abnormality in signal intensity of the cerebral white matter, thalami and basal ganglia. Other manifestations may include macrocephaly, dilated cardiomyopathy, arrhythmias, hepatomegaly and acute pancreatitis. Children are usually healthy between episodes; subsequent acute crises may be preceded by anorexia, lethargy, behavioral changes, irritability and muscle weakness. Hypoketotic hypoglycemia is characteristic.
## Etiology
3HMG is caused by mutations of the gene HMGCL (1p36.11).
## Diagnostic methods
Diagnosis is based on the tandem mass spectrometry profile of plasmatic acylcarnitines (increased C5OH and C6DC) and urinary organic acid (high levels of acids: 3-hydroxy-3-methylglutaric, 3-hydroxyisovaleric, 3-methylglutaconic and 3-methyglutaric). The diagnosis can be confirmed by mutation analysis.
## Differential diagnosis
Differential diagnosis includes sepsis, fatty acid oxidation disorders, organic acidurias and Reye's syndrome.
## Antenatal diagnosis
During the third trimester of gestation, amniotic fluid organic acid levels, as well as maternal urinalysis may indicate 3HMG; confirmation requires testing of cultured amniocytes or chorionic villi for molecular study.
## Genetic counseling
3HMG is an autosomal recessive genetic disorder. Genetic counselling should be offered to all families.
## Management and treatment
Patients must be treated by intravenous 10% glucose and supportive treatment during acute metabolic crises. Maintenance treatment requires protein/leucine-restricted diet with a leucine free amino acid mixture, restricted fat intake and regular feeding (every 3-6 hours). Carnitine supplementation is often given.
## Prognosis
Prognosis is good for those patients who are rapidly diagnosed and survive past childhood.
*[v]: View this template
*[t]: Discuss this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| 3-hydroxy-3-methylglutaric aciduria | c0268601 | 3,688 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=20 | 2021-01-23T19:09:32 | {"gard": ["8387"], "mesh": ["C538324"], "omim": ["246450"], "umls": ["C0268601", "C1533587"], "icd-10": ["E71.1"], "synonyms": ["3-hydroxy-3-methylglutaryl-CoA lyase deficiency", "HMG-CoA lyase deficiency", "Hydroxymethylglutaric aciduria"]} |
Juvenile polyposis syndrome (JPS) is a disorder characterized by having a susceptibility to developing hamartomatous polyps in the gastrointestinal (GI) tract. A hamartomatous polyp is a benign (noncancerous) tumor-like malformation made up of an abnormal mixture of cells and tissues. In JPS, these polyps can occur in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp and not the age at which the polyps develop.
Most people with JPS have some polyps by the age of age 20. The number of polyps in affected people vary. While some people may have only four or five polyps over their lifetime, others (even in the same family) may have more than 100. If the polyps are left untreated, they can result in bleeding and anemia. Most juvenile polyps are benign, although over time they can become cancerous. In families with JPS, the risk for developing a GI cancer ranges from 9% to 50%. Most of this risk is due to colon cancer. The incidence of colorectal cancer in people with JPS is 17%-22% by the age of 35 and as high as 68% by the age of 60. Cancers of the stomach, upper GI tract, and pancreas have also been observed. To date, mutations in two genes are known to cause JPS: BMPR1A and SMAD4.
Management of JPS includes routine colonoscopy with removal of any polyps to reduce the risk of bleeding, intestinal obstruction, and colon cancer. When the number of polyps is large, removal of all or part of the colon or stomach may become needed. Additional screening can include upper endoscopy, complete blood count, and monitoring for symptoms such as rectal bleeding and/or anemia abdominal pain, constipation, diarrhea, or change in stool size, shape, and/or color.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Juvenile polyposis syndrome | c0345893 | 3,689 | gard | https://rarediseases.info.nih.gov/diseases/3065/juvenile-polyposis-syndrome | 2021-01-18T17:59:39 | {"mesh": ["C537702"], "omim": ["174900"], "umls": ["C0345893"], "orphanet": ["2929"], "synonyms": ["JPS", "Polyposis juvenile intestinal", "PJI", "Juvenile intestinal polyposis", "JIP", "Polyposis familial of entire gastrointestinal tract"]} |
"MdDS" redirects here. For other uses, see MDDS.
Mal de debarquement
Other namesIllness of disembarkment[1]
Mal de debarquement (or mal de débarquement) syndrome (MdDS, or common name disembarkment syndrome) is a neurological condition usually occurring after a cruise, aircraft flight, or other sustained motion event. The phrase "mal de débarquement" is French and translates to "illness of disembarkment". MdDS is typically diagnosed by a Neurologist or an Ear Nose & Throat specialist when a person reports a persistent rocking, swaying, or bobbing feeling (though they are not necessarily rocking). This usually follows a cruise or other motion experience. Because most vestibular testing proves to be negative, doctors may be baffled as they attempt to diagnose the syndrome. A major diagnostic indicator is that most patients feel better while driving or riding in a car, i.e, while in passive motion. MdDS is unexplained by structural brain or inner ear pathology and most often corresponds with a motion trigger, although it can occur spontaneously. This differs from the very common condition of "land sickness" that most people feel for a short time after a motion event such as a boat cruise, aircraft ride, or even a treadmill routine which may only last minutes to a few hours. The syndrome has recently received increased attention due to the number of people presenting with the condition and more scientific research has commenced in determining what triggers MdDS and how to cure it.
## Contents
* 1 Symptoms
* 2 Diagnosis
* 3 Treatment
* 4 Epidemiology
* 5 Research
* 5.1 Repetitive transcranial magnetic stimulation
* 5.2 Vestibulo-Ocular Reflex Research 2014
* 6 See also
* 7 References
## Symptoms[edit]
Common symptoms most frequently reported include a persistent sensation of motion usually described as rocking, swaying, or bobbing, disequilibrium with difficulty maintaining balance; it is seldom accompanied by a true spinning vertigo. Chronically fatigued, sufferers can become fatigued quickly with minimal exertion and some might experience neck and back pain. Other symptoms include the feeling of pressure in the brain, mostly around the frontal lobe area, headaches and/or migraine headaches, ophthalmodynia periodica (ice pick stabbing headaches in the early stages of MdDs), ear pain, ear fullness and possibly tinnitus.[citation needed]
Fluctuations in weather also affect sufferers, in particularly hot weather and barometric pressure changes. Many have photo-sensitivity and find it more difficult to walk in the dark as well as other sensitivities to strong smells including chemical smells. Cognitive impairment ("brain fog") includes an inability to recall words, short term memory loss, an inability to multi-task, misspelling and mispronunciation of words, difficulty in concentrating. Many MdDS sufferers report they are unable to use a computer for any length of time due to the visual over-stimulation, and some are even unable to watch television.[citation needed]
Symptoms can be increased by stress, lack of sleep, crowds, flickering lights, loud sounds, fast or sudden movements, enclosed areas and visual intolerance of busy patterns and scrolling movement.[citation needed]
MdDS sufferers may have hypersomnia and can sleep up to 12 or more hours a day, depending on their symptom levels. Research reveals MdDS is not migraine-related and many sufferers have never had migraine symptoms prior to the onset of the disorder.[2] However, for some MdDS sufferers there maybe have been a correlation between migraine and some pathophysiological overlap or even some other precipitating illness.[citation needed]
The condition may be masked by a return to motion such as in a car, train, plane, or boat; however, once the motion ceases, the symptoms rebound or return, often at much higher levels than when the journey first commenced.[citation needed]
The symptoms of MdDS may be extremely debilitating and fluctuate high and low on a daily basis; it greatly affects the daily life and working capacity of sufferers with many having to relinquish work; it also limits most other daily and social activities. Sufferers can have low quality of life in both the physical and emotional realms, comparable to people who have multiple sclerosis with many symptoms being of a similar nature. High levels of disequilibrium can contribute to suffers not being able to drive a car or walk far and this can create varying levels of anxiety in some or possibly depression due to the significant level of disability.[citation needed]
## Diagnosis[edit]
MdDS is diagnosed several ways, one being by the symptoms: in particular, the "constant rocking, swaying feeling" and the abatement of this feeling when in motion again and as a matter of exclusion.[3] There are no definitive tests that confirm MdDS, only tests that rule out other conditions. Tests include hearing and balance, and MdDS is generally diagnosed by either a neurologist or an ear, nose, and throat specialist.[3]
## Treatment[edit]
There is no known cure for MdDS, as with most balance and gait disorders, some form of displacement exercise is thought helpful (for example walking, jogging, or bicycling but not on a treadmill or stationary bicycle). This has not been well-studied in MdDS. Medications that suppress the nerves and brain circuits involved in balance (for example, the benzodiazepine clonazepam) have been noted to help and can lower symptoms; however, it is not a cure. It is not known whether a medication that suppresses symptoms prolongs symptom duration or not. Vestibular therapy has not proved to be effective in treating MdDS.[4]
Additional research is being undertaken into the neurological nature of this syndrome through imaging studies. Many sufferers of this syndrome have found relief by taking histamine blockers or antihistamines (Benadryl for instance). A single Benadryl gel tab at the beginning of the flight and at each 4-hour interval for longer flight.[medical citation needed]
## Epidemiology[edit]
The condition is thought to be under-reported in the medical literature. A study of 27 cases conducted by Timothy C Hain in 1999 noted all but one patient to be female. The average age in this series was 49 years.[5] This apparent gender disparity, however, may be due in part to the fact that the questionnaire which formed the basis of the study was circulated in a publication with a predominantly female reader base.[5]
Subsequent studies have produced conflicting results with regard to the gender distribution of MdDS. The trends in Hain's report have recently been supported by the MdDS Balance Disorder Foundation,[6] in a study of over 100 individuals diagnosed with MdDS. The female:male ratio was approximately 9:1; the average age of onset was 43–45 years. However, another recent study found that 44% of subjects who had experienced MdDS for 2 years or more were male,[7] suggesting a more even distribution.
It has been shown to occur in excursions of as little as 30 minutes though it has been unclear how long it takes for symptoms to occur.[3] The most commonly reported inciting event was a prolonged ocean cruise (~45%); however, shorter boating excursions (~22%), aircraft travel (~15%), and automobile travel (~8%) have all been described.[citation needed]
Mal de Débarquement syndrome has been noted as far back to the times of Erasmus Darwin in 1796,[4] and Irwin J A (1881) "The pathology of seasickness".
Cases of MdDS have been reported in children as young as eight and in both genders. Men may have a more difficult time obtaining a diagnosis due to the disparity of women reported. When sailors and soldiers returned from World War II, the syndrome was reported at a higher rate in males[citation needed]
## Research[edit]
### Repetitive transcranial magnetic stimulation[edit]
Despite MdDS causing significant disability, therapy for persistent MdDS remains virtually nonexistent. A pilot study has commenced utilizing repetitive transcranial magnetic stimulation (rTMS) this being a method of neuromodulation in which a local magnetic field is applied over the scalp to induce an electric current in the cortical structures underlying the coil. Low-frequency rTMS (e1 Hz) induces local inhibition, whereas high frequency rTMS (Q5 Hz) induces local excitation. The TMS studies have proved to help in lowering the symptoms of MdDS if the treatment is ongoing; however, it is not a cure.[citation needed]
### Vestibulo-Ocular Reflex Research 2014[edit]
At least one clinical trial on readaptation of the vestibulo-ocular reflex undertaken by Dr Mingjia Dai from Mount Sinai Hospital in New York City has produced results for a significant percentage of patients who have participated in the program.[8]
Dr Dai has developed an intervention that provided improvement in symptoms for 70% of the patients in the clinical trial phase.[8] The protocol involves a physical manipulation of the patient intended to readapt the vestibulo-ocular reflex. While the program is no longer in the research phase, Dai continues to accept patients. According to Dai, "success" is measured as a 50% reduction of symptoms.[9]
Recent research reveals a very small percentage of MdDS cases may be related to optokinetic nystagmus (OKN).
## See also[edit]
* Motion sickness (seasickness, travel sickness)
* Space adaptation syndrome (Space flight "zero-g" and return)
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Mal de débarquement". www.orpha.net. Retrieved 24 May 2019.
2. ^ Cha YH (2009). "Mal de debarquement". Semin Neurol. 29 (5): 520–7. doi:10.1055/s-0029-1241038. PMC 2846419. PMID 19834863.
3. ^ a b c Clinton R. Gibbs; Katherine H. Commons; Lawrence H. Brown & Denise F. Blake (2010). "'Sea legs': sharpened Romberg test after three days on a live-aboard dive boat". Diving and Hyperbaric Medicine. 40 (4): 189–194. PMID 23111933.
4. ^ a b Hain, Timothy C. "Mal de Debarquement Syndrome (MdDS or MdDS)". dizziness-and-balance.com. Retrieved 22 July 2015.
5. ^ a b Timothy C. Hain; Philip A. Hanna & Mary A. Rheinberger (Jun 1999), "Mal de debarquement", Archives of Otolaryngology–Head & Neck Surgery, 125 (6): 615–620, doi:10.1001/archotol.125.6.615, PMID 10367916
6. ^ "Understanding Mal de Débarquement Syndrome". MdDS Balance Disorder Foundation. Retrieved 2013-05-14.
7. ^ Y.-H. Cha; J. Brodsky; G. Ishiyama; C. Sabatti & R. W. Baloh (2008). "Clinical features and associated syndromes of mal de debarquement". Journal of Neurology. 255 (7): 1038–44. doi:10.1007/s00415-008-0837-3. PMC 2820362. PMID 18500497. NIHMS174090.
8. ^ a b Dai M, Cohen B, Smouha E, Cho C (2014). "Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome". Front Neurol. 5: 124. doi:10.3389/fneur.2014.00124. PMC 4097942. PMID 25076935.
9. ^ "Q & A – MdDS". Icahn School of Medicine at Mount Sinai.
Classification
D
* ICD-10: H81.8
* MeSH: C537840
External resources
* Orphanet: 210272
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Mal de debarquement | c1608983 | 3,690 | wikipedia | https://en.wikipedia.org/wiki/Mal_de_debarquement | 2021-01-18T18:49:12 | {"gard": ["6959"], "mesh": ["C537840"], "umls": ["C1608983"], "orphanet": ["210272"], "wikidata": ["Q3480741"]} |
Focal segmental glomerulosclerosis (FSGS) is a type of kidney disorder. It is characterized by scar tissue that forms in some of the glomeruli in the kidney. FSGS may cause non-specific signs and symptoms, including protein in the urine, elevated levels of creatinine, and swelling. In many cases the cause of FSGS can not be determined. Some cases are thought to be associated with congenital kidney defects, urine backing up into the kidneys, obesity, obstructive sleep apnea, sickle cell anemia, or viruses (e.g., HIV). The goal of treatment is to control symptoms and prevent chronic kidney failure. Even with treatment, many people with FSGS progress to kidney failure within 5 to 20 years.
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Focal segmental glomerulosclerosis | c0017668 | 3,691 | gard | https://rarediseases.info.nih.gov/diseases/6517/focal-segmental-glomerulosclerosis | 2021-01-18T18:00:27 | {"mesh": ["D005923"], "synonyms": ["FSGS", "Glomerulosclerosis, focal", "Segmental glomerulosclerosis", "Focal sclerosis with hyalinosis", "Familial idiopathic nephrotic syndrome", "Familial idiopathic steroid-resistant nephrotic syndrome"]} |
The disorder seems to begin rarely in early infancy. However, the paucity of myelin in the cerebral hemispheres during the first 4 to 6 months of life would make histopathologic classification on the basis of myelin breakdown difficult at this stage. Progression is usually subacute in pace. Cortical blindness is often a conspicuous feature. Sibs may show great differences in the site of the lesion, age of onset, and rate of progression (Meyer and Pilkington, 1936). All cases reported as familial Schilder disease are probably in fact sudanophilic cerebral sclerosis, Krabbe disease (245200), or metachromatic leukoencephalopathy (250100). If the term is to be preserved at all, its use should be confined to sudanophilic cerebral sclerosis. (The neurologic disorder in adrenoleukodystrophy is also referred to as Schilder disease (300100).)
Neuro \- Cortical blindness Lab \- Sudanophilic cerebral sclerosis Inheritance \- Autosomal recessive \- ? not a distinct disorder. See Krabbe disease (245200), metachromatic leukoencephalopathy (250100) and X-linked adrenoleulodystrophy (300100) ▲ Close
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| SUDANOPHILIC CEREBRAL SCLEROSIS | c0007795 | 3,692 | omim | https://www.omim.org/entry/272100 | 2019-09-22T16:21:59 | {"mesh": ["D002549"], "omim": ["272100"], "icd-9": ["341.1"], "icd-10": ["G37.0"], "orphanet": ["59298"], "synonyms": ["Alternative titles", "SCHILDER DISEASE"]} |
A rare genetic neurometabolic disease characterized by childhood onset of global developmental delay, progressive spastic ataxia leading to loss of independent ambulation, and elevated plasma levels of glutamine. Optic atrophy, tremor, and dysarthria have also been reported. Brain imaging may show cerebellar atrophy.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Spastic ataxia-dysarthria due to glutaminase deficiency | None | 3,693 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=557056 | 2021-01-23T17:03:01 | {"icd-10": ["G11.1"]} |
A rare ciliopathy with major skeletal involvement characterized by short ribs and extremely narrow thorax, severely shortened tubular bones with round metaphyseal ends and lateral spikes, and anomalies of multiple organs such as the heart, kidneys, liver, pancreas, intestine, and genitalia, with occasional occurrence of situs inversus totalis. Cleft lip/palate and polydactyly may also be present. The syndrome is fatal prenatally or in the perinatal period.
*[v]: View this template
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Short rib-polydactyly syndrome, Verma-Naumoff type | c0432197 | 3,694 | orphanet | https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93271 | 2021-01-23T17:07:15 | {"gard": ["4835"], "mesh": ["C537602"], "omim": ["613091", "614091", "615503", "615633"], "umls": ["C0432197"], "icd-10": ["Q77.2"], "synonyms": ["Short rib-polydactyly syndrome type 3"]} |
This article includes a list of general references, but it remains largely unverified because it lacks sufficient corresponding inline citations. Please help to improve this article by introducing more precise citations. (February 2014) (Learn how and when to remove this template message)
Steroid diabetes
Other namessteroid-induced diabetes
Steroid diabetes is a medical term referring to prolonged hyperglycemia due to glucocorticoid therapy for another medical condition. It is usually, but not always, a transient condition.
## Contents
* 1 Cause
* 2 Mechanism
* 3 Diagnosis
* 3.1 Criteria
* 4 Treatment
* 5 References
## Cause[edit]
The most common glucocorticoids which cause steroid diabetes are prednisolone and dexamethasone given systemically in "pharmacologic doses" for days or weeks. Typical medical conditions in which steroid diabetes arises during high-dose glucocorticoid treatment include severe asthma, organ transplantation, cystic fibrosis, inflammatory bowel disease, and induction chemotherapy for leukemia or other cancers.
## Mechanism[edit]
Glucocorticoids oppose insulin action and stimulate gluconeogenesis, especially in the liver, resulting in a net increase in hepatic glucose output. Most people can produce enough extra insulin to compensate for this effect and maintain normal glucose levels, but those who cannot develop steroid diabetes.
## Diagnosis[edit]
Steroid diabetes must be distinguished from stress hyperglycemia, hyperglycemia due to excessive intravenous glucose, or new-onset diabetes of another type. Because it is not unusual for steroid treatment to precipitate type 1 or type 2 diabetes in a person who is already in the process of developing it, it is not always possible to determine whether apparent steroid diabetes will be permanent or will go away when the steroids are finished. More commonly undiagnosed cases of type 2 diabetes are brought to clinical attention with corticosteroid treatment because subclinical hyperglycemia worsens and becomes symptomatic. Generally, steroid diabetes without preexisting type 2 diabetes will resolve upon termination of corticosteroid administration.
Steroid diabetes does not occur with other steroid hormones, such as anabolic steroids or sex steroids because these other categories of steroids have actually shown to have positive effects on glucose metabolism.
### Criteria[edit]
The diagnostic criteria for steroid diabetes are those of diabetes (fasting glucoses persistently above 125 mg/dl (7 mM) or random levels above 200 mg/dl (11 mM)) occurring in the context of high-dose glucocorticoid therapy. Insulin levels are usually detectable, and sometimes elevated, but inadequate to control the glucose. In extreme cases the hyperglycemia may be severe enough to cause nonketotic hyperosmolar coma.
## Treatment[edit]
Treatment depends on the severity of the hyperglycemia and the estimated duration of the steroid treatment. Mild hyperglycemia in an immunocompetent patient may not require treatment if the steroids will be discontinued in a week or two. Moderate hyperglycemia carries an increased risk of infection, especially fungal, and especially in people with other risk factors such as immunocompromise or central intravenous lines. Insulin is the most common treatment.
## References[edit]
* Steroid-Induced Diabetes Mellitus and Related Risk Factors in Patients With Neurologic Disease \- MedScape
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Steroid diabetes | c0342269 | 3,695 | wikipedia | https://en.wikipedia.org/wiki/Steroid_diabetes | 2021-01-18T19:07:13 | {"umls": ["C0342269"], "wikidata": ["Q7611608"]} |
Type of medical trauma
This article is written like a manual or guidebook. Please help rewrite this article from a descriptive, neutral point of view, and remove advice or instruction. (March 2018) (Learn how and when to remove this template message)
Worker hanging strapped into a safety harness during a fall rescue drill
Suspension trauma (Syn. "orthostatic shock while suspended"), also known as harness hang syndrome (HHS), suspension syndrome, or orthostatic intolerance, is an effect which occurs when the human body is held upright without any movement for a period of time. If the person is strapped into a harness or tied to an upright object they will eventually suffer the central ischaemic response (commonly known as fainting). Fainting while remaining vertical increases the risk of death from cerebral hypoxia.[1] Since there is no evidence that these effects are specifically due to trauma, or caused by the harness itself, climbing medicine authorities have argued against the terminology of suspension trauma or harness hang syndrome and instead termed this simply "suspension syndrome". [2]
People at risk of suspension trauma include people using industrial harnesses (fall arrest systems, abseiling systems, confined space systems), people using harnesses for sporting purposes (caving, climbing, parachuting, etc.), stunt performers, circus performers, and occupations that require the use of harnesses and suspension systems in general. Suspension shock can also occur in medical environments, for similar reasons.[citation needed]
In the UK the term "suspension trauma" has been replaced by "syncope" or "pre-syncope" as "trauma" suggests that there has been a physical injury that has resulted in the fallen person becoming unconscious. In the circumstances where a person has fallen into suspension on a rope/lanyard and has become unconscious, it is thought that the unconscious state "syncope" is due to a combination of orthostasis or motionless vertical suspension, with "pre-syncope" being the state before the person becomes unconscious where the fallen person may experience symptoms such as light-headedness; nausea; sensations of flushing; tingling or numbness of the arms or legs; anxiety; visual disturbance; or faintness. HSE Research Report RR708 2009 1 Introduction page 5 paragraphs 1 and 3 refers.
## Contents
* 1 Cause
* 2 Symptoms
* 3 Treatment
* 4 Prevention
* 5 See also
* 6 References
* 7 External links
## Cause[edit]
The most common cause is accidents in which the person remains motionless suspended in a harness for longer periods of time. Motionlessness may have several causes including fatigue, hypoglycemia, hypothermia or traumatic brain injury.
## Symptoms[edit]
Onset of symptoms may be after just a few minutes, but usually occurs after at least 20 minutes of free hanging. Typical symptoms are pallor, sweating, shortness of breath, blurred vision, dizziness, nausea, hypotension and numbness of the legs. Eventually it leads to fainting, which may result in death due to oxygen deprivation of the brain.
## Treatment[edit]
If someone is stranded in a harness, but is not unconscious or injured, and has something to kick against or stand on (such as a rock ledge or caving leg-loops) it is helpful for them to use their leg muscles by pushing against it every so often, to keep the blood pumping back to the torso. If the person is stranded in mid-air or is exhausted, then keeping the legs moving can be both beneficial and rather dangerous. On the one hand, exercising the leg muscles will keep the blood returning to the torso, but on the other hand, as the movements become weaker the leg muscles will continue to demand blood yet they will become much less effective at returning it to the body, and the moment the victim ceases moving their legs, the blood will immediately start to pool. "Pedaling an imaginary bicycle" should only be used as a last-ditch effort to prolong consciousness, because as soon as the "pedaling" stops, fainting will shortly follow. If it is impossible to rescue someone immediately, then it is necessary to raise their legs to a sitting position, which can be done with a loop of rigging tape behind the knees or specialized equipment from a rescue kit.
When workers are suspended in their safety harnesses for long periods, they may suffer from blood pooling in the lower body. This can lead to suspension trauma. Once a worker is back on the ground after a fall has been arrested on a fall protection system, a worker should be placed in the “W” position. The “W” position is where a worker sits upright on the ground with their back/chest straight and their legs bent so that their knees are in line with the bottom of their chin. For added stability, make sure that the worker’s feet stay flat on the ground. In this position, a KED board can still be used if there are any potential spinal injuries and a worker needs stabilization before transport.
Once the worker is in this position, they will need to stay in that position for at least 30 minutes. Try to leave the worker in this position until their symptoms begin to subside. The time in the “W” position will allow the pooled blood from the legs to be slowly re-introduced back into the body. By slowing the rate at which the pooled blood reaches different organs, you are giving the body more of an opportunity to filter the pooled blood and maintain internal homeostasis. http://www.rigidlifelines.com/blog/entry/suspension-traumasymptoms-and-treatment
## Prevention[edit]
Prevention of suspension trauma is preferable to dealing with its consequences. Specific recommendations for individuals doing technical ropework are to avoid exhausting themselves so much that they end up without the energy to keep moving, and making sure everyone in a group is trained in single rope rescue techniques, especially the "single rope pickoff", a rather difficult technical maneuver that must be practiced frequently for smooth performance.
## See also[edit]
* Reflow syndrome, which occurs when toxins that accumulated in pooled blood suddenly return to the body when the person lies down following suspension trauma
* Compartment syndrome, a dangerous condition that sometimes occurs with suspension trauma
## References[edit]
1. ^ Seddon P.: Harness suspension: review and evaluation of existing information. In: Health and Safety Executive - CONTRACT RESEARCH REPORT 451/2002, page 3, hier online
2. ^ Hawkins SC, Simon RB, Beissinger JP, Simon D. Vertical Aid: Essential Wilderness Medicine for Climbers, Trekkers, and Mountaineers. New York: The Countryman Press, 2017.
## External links[edit]
* Suspension Trauma Article on the Prevention and Treatment of Suspension Trauma
* Harness suspension: review and evaluation of existing information
* Harness Hang Syndrome: Fact and Fiction
* Will Your Safety Harness Kill You?, from Occupational Health & Safety magazine, Vol. 27, No. 3, pages 86–90, March 2003
* Evidence-based review of the current guidance on first aid measures for suspension trauma
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Suspension trauma | None | 3,696 | wikipedia | https://en.wikipedia.org/wiki/Suspension_trauma | 2021-01-18T19:02:46 | {"wikidata": ["Q1642307"]} |
Malpuech facial clefting syndrome
SpecialtyMedical genetics
Malpuech facial clefting syndrome, also called Malpuech syndrome or Gypsy type facial clefting syndrome,[1] is a rare congenital syndrome. It is characterized by facial clefting (any type of cleft in the bones and tissues of the face, including a cleft lip and palate), a caudal appendage (a "human tail"),[2][3] growth deficiency, intellectual and developmental disability, and abnormalities of the renal system (kidneys) and the male genitalia.[4] Abnormalities of the heart, and other skeletal malformations may also be present.[5] The syndrome was initially described by Georges Malpuech and associates in 1983.[6] It is thought to be genetically related to Juberg-Hayward syndrome. Malpuech syndrome has also been considered as part of a spectrum of congenital genetic disorders associated with similar facial, urogenital and skeletal anomalies. Termed "3MC syndrome", this proposed spectrum includes Malpuech, Michels and Mingarelli-Carnevale (OSA) syndromes.[7][8] Mutations in the COLLEC11 and MASP1 genes are believed to be a cause of these syndromes.[9] The incidence of Malpuech syndrome is unknown. The pattern of inheritance is autosomal recessive, which means a defective (mutated) gene associated with the syndrome is located on an autosome, and the syndrome occurs when two copies of this defective gene are inherited.[10]
## Contents
* 1 Characteristics
* 2 Genetics
* 3 Diagnosis
* 3.1 Classification
* 4 Management
* 5 History
* 6 References
* 7 External links
## Characteristics[edit]
A typical cleft lip, seen in a five-month-old infant.
The bilateral type of cleft lip has been reported in Malpuech syndrome.
Malpuech syndrome is congenital, being apparent at birth. It is characterized by a feature known as facial clefting. Observed and noted in the initial description of the syndrome as a cleft lip and palate,[6] facial clefting is identified by clefts in the bones, muscles and tissues of the face, including the lips and palate. The forms of cleft lip and palate typically seen with Malpuech syndrome are midline (down the middle of the lip and palate)[11] or bilateral (affecting both sides of the mouth and palate).[10] Facial clefting generally encompasses a wide range of severity, ranging from minor anomalies such as a bifid (split) uvula, to a cleft lip and palate, to major developmental and structural defects of the facial bones and soft tissues.[12] Clefting of the lip and palate occurs during embryogenesis.[13][14] Additional facial and ortho-dental anomalies that have been described with the syndrome include: hypertelorism (unusually wide-set eyes, sometimes reported as telecanthus), narrow palpebral fissures (the separation between the upper and lower eyelids) and ptosis (drooping) of the eyelids, frontal bossing (prominent eyebrow ridge) with synophris, highly arched eyebrows, wide nasal root and a flattened nasal tip, malar hypoplasia (underdeveloped upper cheek bone), micrognathia (an undersized lower jaw), and prominent incisors. Auditory anomalies include an enlarged ear ridge, and hearing impairment associated with congenital otitis media (or "glue ear", inflammation of the middle ear) and sensorineural hearing loss.[4][15][16]
Another feature identified with Malpuech syndrome is a caudal appendage.[1][3] A caudal appendage is a congenital outgrowth stemming from the coccyx (tailbone). Present in many non-human animal species as a typical tail, this feature when seen in an infant has been described as a "human tail".[2][17] This was observed by Guion-Almeida (1995) in three individuals from Brazil. The appendage on X-rays variously appeared as a prominent protrusion of the coccyx.[3] On a physical examination, the appendage resembles a nodule-like stub of an animal tail.[18]
Deficiencies such as mental retardation, learning disability, growth retardation and developmental delay are common. Psychiatric manifestations that have been reported with the syndrome include psychotic behavior, obsessive–compulsive disorder, loss of inhibition, hyperactivity, aggression, fear of physical contact, and compulsive actions like echolalia (repeating the words spoken by another person). Neuromuscular tics have also been noted.[4][15]
Urogenital abnormalities, or those affecting the urinary and reproductive systems, are common with the syndrome. Malpuech et al. (1983) and Kerstjens-Frederikse et al. (2005) reported variously in affected males a micropenis, hypospadias (a congenital mislocation of the urinary meatus), cryptorchidism (ectopic or undescended testes), bifid (split) and underdeveloped scrotum, and an obstructive urethral valve.[4][6] An affected boy was also reported by Reardon et al. (2001) with left renal agenesis, an enlarged and downwardly displaced right kidney, cryptorchidism and a shawl scrotum.[7] Other malformations that have been noted with the syndrome are omphalocele[3] and an umbilical hernia.[19]
Diagram of a neonatal heart affected by PDA
Congenital abnormalities of the heart have also been observed with Malpuech syndrome. From a healthy Japanese couple, Chinen and Naritomi (1995) described the sixth child who had features consistent with the disorder. This two-month-old male infant was also affected by cardiac anomalies including patent ductus arteriosus (PDA)[20] and ventricular septal defect.[5] The opening in the ductus arteriosus associated with PDA had been surgically repaired in the infant at 38 days of age. A number of minor skeletal aberrations were also reported in the infant, including wormian bones at the lambdoid sutures.[5]
## Genetics[edit]
Malpuech facial clefting syndrome has an autosomal recessive pattern of inheritance.
Malpuech syndrome, as with the other disorders within the 3MC syndrome consideration, is caused by mutations in the COLLEC11 and MASP1 genes. In an investigation by Rooryck et al. (2011), eleven families affected by 3MC syndrome were studied, which resulted in the identification of these two mutations. Both genes encode proteins of the lectin complement pathway, which plays a role in the complement system of innate, or non-specific immunity in humans and other species.[9]
The COLLEC11, or CL-K1 gene is located on the short arm of chromosome 2 (2p25.3) in humans.[21] The CL-K1 protein is a C-type lectin, and belongs to the collectin family of these proteins. Other than its role in innate immunity, the protein is thought to be involved in the development of tissues including craniofacial cartilage, the heart and kidney during embryogenesis. This function in facial development was corroborated through study of the zebrafish, where mutations in its version of CL-K1 contributed to craniofacial abnormalities (such as Craniofacial clefts) possibly associated with errors in neural crest cell migration.[9]
The short and long arm of a typical human chromosome.
The MASP1, or Mannan-binding Serine Protease I gene is located on the long arm of human chromosome 3 at 3q27-q28.[22] The protein is a type of connectin called a mannan-binding lectin, which plays a role in innate immunity by binding to pathogens such as viruses including HIV.[23]
As described by Sirmaci et al. (2010), three Turkish individuals from two consanguineous families (the children of relatives such as cousins are said to be in a consanguineous family) with various characteristics of 3MC syndrome, including facial dysmorphism and a caudal appendage, were evaluated. Investigation of homologous chromosomes through gene mapping revealed an autozygous region (a location on a chromosome where both alleles of a gene originate from a common ancestor) at chromosome 3q27 in both families. In one family, a missense mutation in MASP1 at this location resulted in the replacement of the amino acid glycine by arginine at position 687 in the gene sequence. The mutation cosegregated with the observed phenotype. In individuals from the second family, DNA sequencing of MASP1 showed a nonsense mutation that resulted in a deactivation of tryptophan at position 290 in the gene, that also cosegregated with the phenotype. Both mutations occur in a form of MASP1 known to process IGFBP5; loss of this function associated with mutation of MASP1 causes disruptions in the availability of insulin-like growth factor during craniofacial and musculoskeletal development during the embryonic period. These results indicate that mutations in MASP1 are responsible for an array of features found with malformation disorders including Malpuech syndrome.[24]
The syndrome is inherited in an autosomal recessive manner.[10] This means the defective gene(s) responsible for the disorder (COLLEC11, MASP1) is located on an autosome (chromosomes 2 and 3 are autosomes), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.[citation needed]
## Diagnosis[edit]
It is suggested that the diagnostic criteria for Malpuech syndrome should include cleft lip and/or palate, typical associated facial features, and at least two of the following: urogenital anomalies, caudal appendage, and growth or developmental delay.[25] Due to the relatively high rate of hearing impairment found with the disorder, it too may be considered in the diagnosis. Another congenital disorder, Wolf-Hirschhorn (Pitt-Rogers-Danks) syndrome, shares Malpuech features in its diagnostic criteria. Because of this lacking differentiation, karyotyping (microscopic analysis of the chromosomes of an individual) can be employed to distinguish the two. Whereas deletions in the short arm of chromosome 4 would be revealed with Wolf-Hirschhorn, a karyotype without this aberration present would favor a Malpuech syndrome diagnosis. Also, the karyotype of an individual with Malpuech syndrome alone will be normal.[15]
### Classification[edit]
Malpuech syndrome has been shown to have physical, or phenotypical similarities with several other genetic disorders. A report by Reardon et al. (2001) of a nine-year-old boy exhibiting facial, caudal and urogenital anomalies consistent with Malpuech syndrome, who also had skeletal malformites indicative of Juberg-Hayward syndrome, suggests that the two disorders may be allelic (caused by different mutations of the same gene).[7]
Along with several other disorders that have similar, or overlapping features and autosomal recessive inheritance, Malpuech syndrome has been considered to belong under the designation "3MC syndrome". Titomanlio et al. (2005) described a three-year-old female known to have Michels syndrome. In their review of the physical similarities between Michels, Malpuech and Mingarelli-Carnevale syndromes—particularly the facial appearance including instances of cleft lip and palate, and ptosis, and a similarity of congenital abdominal and urogenital anomalies—they believed the syndromes may represent a spectrum of genetic disorders rather than three individual disorders. They initially suggested this spectrum could be named 3MC (Michels-Malpuech-Mingarelli-Carnevale) syndrome.[8] This conclusion and the name 3MC syndrome was supported by Leal et al. (2008), who reported a brother and sister with an array of symptoms that overlapped the various syndromes.[26] Further assertion of 3MC syndrome was by Rooryck et al. (2011) in an elaboration of its cause.[9]
## Management[edit]
Many of the congenital malformations found with Malpuech syndrome can be corrected surgically. These include cleft lip and palate, omphalocele, urogenital and craniofacial abnormalities, skeletal deformities such as a caudal appendage or scoliosis, and hernias of the umbillicus. The primary area of concern for these procedures applied to a neonate with congenital disorders including Malpuech syndrome regards the logistics of anesthesia. Methods like tracheal intubation for management of the airway during general anesthesia can be hampered by the even smaller, or maldeveloped mouth of the infant. For regional anesthesia, methods like spinal blocking are more difficult where scoliosis is present. In a 2010 report by Kiernan et al., a four-year-old girl with Malpuech syndrome was being prepared for an unrelated tonsillectomy and adenoidectomy. While undergoing intubation, insertion of a laryngoscope, needed to identify the airway for the placement of the endotracheal tube, was made troublesome by the presence of micrognathia attributed to the syndrome. After replacement with a laryngoscope of adjusted size, intubation proceeded normally. Successful general anesthesia followed.[16]
A rare follow-up of a male with Malpuech syndrome was presented by Priolo et al. (2007). Born at term from an uneventful pregnancy and delivery, the infant underwent a surgical repair of a cleft lip and palate. No problems were reported with the procedure. A heart abnormality, atrial septal defect, was also apparent but required no intervention. At age three years, mental retardation, hyperactivity and obsessive compulsive disorder were diagnosed; hearing impairment was diagnosed at age six, managed with the use of hearing aids. Over the course of the decade that followed, a number of psychiatric evaluations were performed. At age 14, he exhibited a fear of physical contact; at age 15, he experienced a severe psychotic episode, characterized by agitation and a loss of sociosexual inhibition. This array of symptoms were treated pharmocologically (with prescription medications). He maintained a low level of mental deficiency by age 17, with moments of compulsive echolalia.[15]
## History[edit]
The incidence of Malpuech syndrome has not been determined.[16] A 1999 report by Crisponi et al. suggested that only about 12 individuals worldwide were affected by the disorder at that time.[19] The syndrome was first reported by Guilliaume Malpuech and colleagues in 1983, observed in four children of unspecified gender in what was described as a gypsy family. The children included three siblings and their first cousin; the family was known to be highly consanguineous.[6][15]
## References[edit]
1. ^ a b Online Mendelian Inheritance in Man (OMIM): Malpuech facial clefting syndrome - 248340
2. ^ a b Adeleye, A. O.; Olowookere, K. G. (Sep–Oct 2010). "A Human Tail in an Infant (Letter)". West African Journal of Medicine. 29 (5): 356–358. PMID 21089026.
3. ^ a b c d Guion‐Almeida, M. L. (Jul 1995). "Apparent Malpuech syndrome: Report on three Brazilian patients with additional signs". American Journal of Medical Genetics. 58 (1): 13–17. doi:10.1002/ajmg.1320580104. PMID 7573149.
4. ^ a b c d Kerstjens-Frederikse, W. S.; Brunner, H. G.; Van Dael, C. M.; Van Essen, A. J. (May 2005). "Malpuech syndrome: Three patients and a review". American Journal of Medical Genetics Part A. 134 (4): 450–453. doi:10.1002/ajmg.a.30662. PMID 15793834.
5. ^ a b c Chinen, Y.; Naritomi, K. (Dec 1995). "Malpuech facial clefting syndrome in a Japanese boy with cardiac defects". The Japanese Journal of Human Genetics. 40 (4): 335–338. doi:10.1007/BF01900601. PMID 8851768.
6. ^ a b c d Malpuech, G.; Demeocq, F.; Palcoux, J. B.; Vanlieferinghen, P.; Opitz, J. M. (Dec 1983). "A previously undescribed autosomal recessive multiple congenital anomalies/mental retardation (MCA/MR) syndrome with growth failure, lip/palate cleft(s), and urogenital anomalies". American Journal of Medical Genetics. 16 (4): 475–480. doi:10.1002/ajmg.1320160405. PMID 6660246.
7. ^ a b c Reardon, W.; Hall, C. M.; Gorman, W. (Apr 2001). "An atypical case suggesting the possibility of overlap between Malpuech and Juberg-Hayward syndromes". Clinical Dysmorphology. 10 (2): 123–128. doi:10.1097/00019605-200104000-00009. PMID 11310992.
8. ^ a b Titomanlio, L.; Bennaceur, S.; Bremond-Gignac, D.; Baumann, C.; Dupuy, O.; Verloes, A. (Sep 2005). "Michels syndrome, Carnevale syndrome, OSA syndrome, and Malpuech syndrome: Variable expression of a single disorder (3MC syndrome)?". American Journal of Medical Genetics Part A. 137A (3): 332–335. doi:10.1002/ajmg.a.30878. PMID 16096999.
9. ^ a b c d Rooryck, C.; Diaz-Font, A.; Osborn, D. P.; Chabchoub, E.; Hernandez-Hernandez, V.; Shamseldin, H.; Kenny, J.; Waters, A.; Jenkins, D.; Kaissi, A. A.; Leal, G. F.; Dallapiccola, B.; Carnevale, F.; Bitner-Glindzicz, M.; Lees, M.; Hennekam, R.; Stanier, P.; Burns, A. J.; Peeters, H.; Alkuraya, F. S.; Beales, P. L. (Mar 2011). "Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome". Nature Genetics. 43 (3): 197–203. doi:10.1038/ng.757. PMC 3045628. PMID 21258343.
10. ^ a b c Turnbull, C.; Lees, M.; Chitty, L. S. (Dec 2006). "Prenatal sonographic diagnosis of Malpuech syndrome". Prenatal Diagnosis. 26 (12): 1121–1123. doi:10.1002/pd.1564. PMID 17019743.
11. ^ "Midline cleft lip in children". Wrongdiagnoysis.com. Retrieved February 27, 2011.
12. ^ "FACE - DIAGNOSIS OF CONGENITAL ABNORMALITIES - THE 18-23 WEEKS SCAN". Centrus.com.br. Archived from the original on November 21, 2010. Retrieved November 16, 2010.
13. ^ "Definition of facial clefting". Medilexicon.com. Retrieved November 7, 2010.
14. ^ "Rare facial cleft: 14-mth-old Hunan boy Kang Kang born with a 'mask'". Whatsonxiamen.com. Retrieved November 8, 2010.
15. ^ a b c d e Priolo, M; Ciccone, R; Bova, I; Campolo, G; Lagana, C; Zuffardi, O (Mar–Apr 2007). "Malpuech syndrome: Broadening the clinical spectrum and molecular analysis by array-CGH". European Journal of Medical Genetics. 50 (2): 139–143. doi:10.1016/j.ejmg.2006.10.004. PMID 17140870.
16. ^ a b c Kiernan, F; Crowe, S (Apr 2010). "Malpuech syndrome: implications for anesthetic management". Pediatric Anesthesia. 20 (4): 370–371. doi:10.1111/j.1460-9592.2010.03271.x. PMID 20470345.
17. ^ Singh, D.; Kumar, B.; Sinha, V.; Bagaria, H. (Sep 2008). "The human tail: rare lesion with occult spinal dysraphism—a case report". Journal of Pediatric Surgery. 43 (9): e41–43. doi:10.1016/j.jpedsurg.2008.04.030. PMID 18778987.
18. ^ Finn and Lynch (2006), illustration, p. 243.
19. ^ a b Crisponi, G.; Marras, A. R.; Corrias, A. (Sep 1999). "Two sibs with Malpuech syndrome". American Journal of Medical Genetics. 86 (3): 294–299. doi:10.1002/(SICI)1096-8628(19990917)86:3<294::AID-AJMG20>3.0.CO;2-2. PMID 10482884.
20. ^ Online Mendelian Inheritance in Man (OMIM): Patent ductus arteriosus - 607411
21. ^ Online Mendelian Inheritance in Man (OMIM): COLLEC11 \- 612502
22. ^ Online Mendelian Inheritance in Man (OMIM): MASP1 \- 600521
23. ^ Ji, X; Gewurz, H; Spear, G (2005). "Mannose binding lectin (MBL) and HIV". Molecular Immunology. 42 (2): 145–52. doi:10.1016/j.molimm.2004.06.015. PMID 15488604.
24. ^ Sirmaci, A.; Walsh, T.; Akay, H.; Spiliopoulos, M.; Şakalar, Y. L. R. M. B.; Hasanefendioğlu-Bayrak, A.; Duman, D.; Farooq, A.; King, M. C.; Tekin, M. (2010). "MASP1 Mutations in Patients with Facial, Umbilical, Coccygeal, and Auditory Findings of Carnevale, Malpuech, OSA, and Michels Syndromes". The American Journal of Human Genetics. 87 (5): 679–686. doi:10.1016/j.ajhg.2010.09.018. PMC 2978960. PMID 21035106.
25. ^ Finn, S. M.; Lynch, S. A. (Oct 2006). "Malpuech syndrome: facial features in the absence of clefting". Clinical Dysmorphology. 15 (4): 243–244. doi:10.1097/01.mcd.0000220621.85896.46. PMID 16957483.
26. ^ Leal, G. F.; Silva, E. O.; Duarte, A. R.; Campos, J. F. (Apr 2008). "Blepharophimosis, blepharoptosis, defects of the anterior chamber of the eye, caudal appendage, radioulnar synostosis, hearing loss and umbilical anomalies in sibs: 3MC syndrome?". American Journal of Medical Genetics Part A. 146A (8): 1059–1062. doi:10.1002/ajmg.a.32252. PMID 18266249.
## External links[edit]
Classification
D
* ICD-10: Q89.8
* ICD-9-CM: 759.7
* OMIM: 248340
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Malpuech facial clefting syndrome | c0796032 | 3,697 | wikipedia | https://en.wikipedia.org/wiki/Malpuech_facial_clefting_syndrome | 2021-01-18T18:44:34 | {"mesh": ["C535704"], "icd-9": ["759.7"], "icd-10": ["Q89.8"], "orphanet": ["2453"], "wikidata": ["Q6744609"]} |
Deafness and myopia syndrome is a disorder that causes problems with both hearing and vision. People with this disorder have moderate to profound hearing loss in both ears that may worsen over time. The hearing loss may be described as sensorineural, meaning that it is related to changes in the inner ear, or it may be caused by auditory neuropathy, which is a problem with the transmission of sound (auditory) signals from the inner ear to the brain. The hearing loss is either present at birth (congenital) or begins in infancy, before the child learns to speak (prelingual).
Affected individuals also have severe nearsightedness (high myopia). These individuals are able to see nearby objects clearly, but objects that are farther away appear blurry. The myopia is usually diagnosed by early childhood.
## Frequency
The prevalence of deafness and myopia syndrome is unknown. Only a few affected families have been described in the medical literature.
## Causes
Deafness and myopia syndrome is caused by mutations in the SLITRK6 gene. The protein produced from this gene is found primarily in the inner ear and the eye. This protein promotes growth and survival of nerve cells (neurons) in the inner ear that transmit auditory signals. It also controls (regulates) the growth of the eye after birth. In particular, the SLITRK6 protein influences the length of the eyeball (axial length), which affects whether a person will be nearsighted or farsighted, or will have normal vision. The SLITRK6 protein spans the cell membrane, where it is anchored in the proper position to perform its function.
SLITRK6 gene mutations that cause deafness and myopia syndrome result in an abnormally short SLITRK6 protein that is not anchored properly to the cell membrane. As a result, the protein is unable to function normally. Impaired SLITRK6 protein function leads to abnormal nerve development in the inner ear and improperly controlled eyeball growth, resulting in the hearing loss and nearsightedness that occur in deafness and myopia syndrome.
### Learn more about the gene associated with Deafness and myopia syndrome
* SLITRK6
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Deafness and myopia syndrome | c3806275 | 3,698 | medlineplus | https://medlineplus.gov/genetics/condition/deafness-and-myopia-syndrome/ | 2021-01-27T08:25:37 | {"gard": ["12844"], "omim": ["221200"], "synonyms": []} |
Wide-based "drunken sailor" gait symptom
Main article: Ataxia
Truncal ataxia
Other namesTrunk ataxia, Ataxic gait[1]
Caused by midline damage to the cerebellar vermis
SpecialtyNeurology
Symptoms"drunken sailor" gait characterised by uncertain starts and stops, falling
CausesSpinocerebellar Ataxia (Lesion in Flocculonodular Lobe OR Vestibulo-cerebellum)
Truncal ataxia (or trunk ataxia) is a wide-based "drunken sailor" gait characterised by uncertain starts and stops, lateral deviations and unequal steps. It is an instability of the trunk and often seen during sitting.[2] It is most visible when shifting position or walking heel-to-toe.[1]
As a result of this gait impairment, falling is a concern in patients with ataxia.[3]
Truncal ataxia affects the muscles closer to the body such as the trunk, shoulder girdle and hip girdle. It is involved in gait stability.[3]
Truncal ataxia is different from appendicular ataxia. Appendicular ataxia affects the movements of the arms and legs. It is caused by lesions of the cerebellar hemispheres.[3]
## Contents
* 1 Causes
* 1.1 Common
* 1.2 Uncommon
* 2 References
* 3 External links
## Causes[edit]
Truncal ataxia is caused by midline damage to the cerebellar vermis. There are at least 34 conditions that cause truncal ataxia.[2]
### Common[edit]
* Alcohol intoxication[1]
* Cerebral infarction[1]
* Cerebral hemorrhage[1]
* Cerebellar ataxia[1]
* Multiple sclerosis[1]
* Friedreich's ataxia[1]
* Drugs such as Benzodiazepines, Lithium, Phenytoin[1]
### Uncommon[edit]
* Adrenoleukodystrophy[4]
* Ataxia oculomotor apraxia type 1[4]
* Branchial myoclonus[4]
* Christianson syndrome[4]
* Dandy–Walker syndrome[4]
* Dysequilibrium syndrome[4]
* Epilepsy[4]
* Episodic ataxia[4]
* Post viral cerebellar ataxia[1]
* Gerstmann–Sträussler–Scheinker syndrome[4]
* Machado–Joseph disease[4]
* Microcephaly[4]
* N-acetylaspartate deficiency[4]
* Neuhauser–Eichner–Opitz syndrome[4]
* Paraneoplastic cerebellar degeneration[1]
* Polymicrogyria[4]
* Rett syndrome[4]
* Spinocerebellar ataxia[4]
* Vertebral dissection[1]
## References[edit]
1. ^ a b c d e f g h i j k l Dennis, Mark; Bowen, William Talbot; Cho, Lucy (2012-01-27). Mechanisms of Clinical Signs - E-Book. pp. 280–281. ISBN 9780729580755.
2. ^ a b "NCBI Truncal ataxia". NCBI. Retrieved March 17, 2019.
3. ^ a b c Blumenfeld H (2002). Neuroanatomy through clinical cases. Sunderland, Mass: Sinauer. pp. 670–671. ISBN 0-87893-060-4.
4. ^ a b c d e f g h i j k l m n o p "human phenotype ontology". Retrieved March 17, 2019.
## External links[edit]
* NIH website
* v
* t
* e
Symptoms and signs relating to movement and gait
Gait
* Gait abnormality
* CNS
* Scissor gait
* Cerebellar ataxia
* Festinating gait
* Marche à petit pas
* Propulsive gait
* Stomping gait
* Spastic gait
* Magnetic gait
* Truncal ataxia
* Muscular
* Myopathic gait
* Trendelenburg gait
* Pigeon gait
* Steppage gait
* Antalgic gait
Coordination
* Ataxia
* Cerebellar ataxia
* Dysmetria
* Dysdiadochokinesia
* Pronator drift
* Dyssynergia
* Sensory ataxia
* Asterixis
Abnormal movement
* Athetosis
* Tremor
* Fasciculation
* Fibrillation
Posturing
* Abnormal posturing
* Opisthotonus
* Spasm
* Trismus
* Cramp
* Tetany
* Myokymia
* Joint locking
Paralysis
* Flaccid paralysis
* Spastic paraplegia
* Spastic diplegia
* Spastic paraplegia
* Syndromes
* Monoplegia
* Diplegia / Paraplegia
* Hemiplegia
* Triplegia
* Tetraplegia / Quadruplegia
* General causes
* Upper motor neuron lesion
* Lower motor neuron lesion
Weakness
* Hemiparesis
Other
* Rachitic rosary
* Hyperreflexia
* Clasp-knife response
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitors
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
| Truncal ataxia | c0427190 | 3,699 | wikipedia | https://en.wikipedia.org/wiki/Truncal_ataxia | 2021-01-18T18:49:48 | {"mesh": ["D001259"], "umls": ["C0427190"], "wikidata": ["Q65083605"]} |
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