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nord_128_4 | Related disorders of Autosomal Dominant Hereditary Ataxia | Symptoms of the following disorders can be similar to these conditions. Comparisons may be useful for a differential diagnosis:Olivopontocerebellar atrophy (OPCA) refers to a group of ataxias characterized by progressive neurological degeneration affecting the cerebellum, the pons and the inferior olives. OPCA may be classified based on clinical, genetic, or neuropathological findings; thus, there are many classifications of the disorder. Many of these cases now fall into the SCA category and the term OPCA is relatively unused nowadays. Among the different classifications, there is wide variation in severity and age of onset. The symptoms of OPCA differ from person to person. Most patients experience difficulty with balance and coordination of the legs and arms (ataxia) and slurred speech (dysarthria). Other symptoms may include muscle spasms or weakness and stiffness of the muscles; numbness or tingling of the hands or feet; shaking (tremor) of the hand or arm; reduction or slowness of movements; loss of thinking and/or memory skills; difficulty controlling the bladder or bowels; and feeling faint when standing up. Some patients also have fatigue and/or trouble with sleep. Generally, symptoms of OPCA begin in mid-adult life and progress slowly over the course of many years. (For more information on this disorder, choose “Olivopontocerebellar Atrophy, Hereditary” as your search term in the Rare Disease Database.)Multiple system atrophy (MSA) refers to three slowly progressive related disorders that affect the central and autonomic nervous systems. The disorders are an ataxic form which primarily affects balance, coordination, and speech; a parkinsonian form, which can resemble Parkinson’s disease because of slow movement and stiff muscles; and a form sometimes called Shy-Drager disease that primarily includes low blood pressure on standing (Orthostatic Hypotension). In all three forms of MSA, the patient can have a drop in blood pressure when the patient stands up, which causes dizziness or momentary blackouts. Other symptoms may include stiffness and rigidity, loss of balance and coordination, impaired speech, breathing and swallowing difficulties, blurred vision, male impotence, constipation and urinary difficulties. Most patients develop dementia late in the course of the disease, which is usually diagnosed in persons over age 50. MSA is twice as common in men as in women. (For more information on this disorder, choose “Multiple System Atrophy” as your seach term in the Rare Disease Database.)Charcot-Marie-Tooth disease is usually inherited as a dominant trait. However, in some families it can occur as a recessive trait or even as an X-linked trait. This hereditary form of peripheral nerve disease is characterized by weakness and atrophy, primarily in the legs. Disappearance of the fatty shield surrounding the nerves (segmental demyelination of peripheral nerves) and associated degeneration of part of the nerve cells (axons) characterize this disorder. When it is passed to offspring as an X-linked trait, it affects males more severely than females. (For more information on this disorder, choose “Charcot-Marie-Tooth disease” as your search term in the Rare Disease Database).Friedreich’s ataxia is an autosomal recessive type of hereditary neuromuscular syndrome characterized by slow degenerative changes of the spinal cord, peripheral nerves and the brain. Dysfunction of the central nervous system affects coordination of the muscles in the limbs. Speech can be affected and numbness or weakness of the arms and legs develop. Heart disease (cardiomyopathy) often occurs later in the disease and there is an increased frequency of diabetes. This syndrome appears to be the most common of the many forms of hereditary ataxia. It usually begins during childhood or the teen years. (For more information on this disorder, choose “Ataxia, Friedreich” as your search term in the Rare Disease Database).Ataxia telangiectasia, also known as Louis-Bar syndrome, is inherited as an autosomal recessive trait. It is a progressive cerebellar ataxia that usually begins during infancy. It involves progressive loss of coordination in the limbs, head and eyes with a below-normal immune response to infections. In later stages, dilated blood vessels (telangiectasias) appear in the eyes and skin. Individuals with this form of ataxia are more susceptible to sinus and lung infections, and are at higher risk for developing certain tumors (neoplasms). Ataxia telangiectasia may be misdiagnosed as Friedreich ataxia until dilated blood vessels appear in the skin (telangiectasias). (For more information on this disorder, choose “Ataxia Telangiectasia” as your search term in the Rare Disease Database). | Related disorders of Autosomal Dominant Hereditary Ataxia. Symptoms of the following disorders can be similar to these conditions. Comparisons may be useful for a differential diagnosis:Olivopontocerebellar atrophy (OPCA) refers to a group of ataxias characterized by progressive neurological degeneration affecting the cerebellum, the pons and the inferior olives. OPCA may be classified based on clinical, genetic, or neuropathological findings; thus, there are many classifications of the disorder. Many of these cases now fall into the SCA category and the term OPCA is relatively unused nowadays. Among the different classifications, there is wide variation in severity and age of onset. The symptoms of OPCA differ from person to person. Most patients experience difficulty with balance and coordination of the legs and arms (ataxia) and slurred speech (dysarthria). Other symptoms may include muscle spasms or weakness and stiffness of the muscles; numbness or tingling of the hands or feet; shaking (tremor) of the hand or arm; reduction or slowness of movements; loss of thinking and/or memory skills; difficulty controlling the bladder or bowels; and feeling faint when standing up. Some patients also have fatigue and/or trouble with sleep. Generally, symptoms of OPCA begin in mid-adult life and progress slowly over the course of many years. (For more information on this disorder, choose “Olivopontocerebellar Atrophy, Hereditary” as your search term in the Rare Disease Database.)Multiple system atrophy (MSA) refers to three slowly progressive related disorders that affect the central and autonomic nervous systems. The disorders are an ataxic form which primarily affects balance, coordination, and speech; a parkinsonian form, which can resemble Parkinson’s disease because of slow movement and stiff muscles; and a form sometimes called Shy-Drager disease that primarily includes low blood pressure on standing (Orthostatic Hypotension). In all three forms of MSA, the patient can have a drop in blood pressure when the patient stands up, which causes dizziness or momentary blackouts. Other symptoms may include stiffness and rigidity, loss of balance and coordination, impaired speech, breathing and swallowing difficulties, blurred vision, male impotence, constipation and urinary difficulties. Most patients develop dementia late in the course of the disease, which is usually diagnosed in persons over age 50. MSA is twice as common in men as in women. (For more information on this disorder, choose “Multiple System Atrophy” as your seach term in the Rare Disease Database.)Charcot-Marie-Tooth disease is usually inherited as a dominant trait. However, in some families it can occur as a recessive trait or even as an X-linked trait. This hereditary form of peripheral nerve disease is characterized by weakness and atrophy, primarily in the legs. Disappearance of the fatty shield surrounding the nerves (segmental demyelination of peripheral nerves) and associated degeneration of part of the nerve cells (axons) characterize this disorder. When it is passed to offspring as an X-linked trait, it affects males more severely than females. (For more information on this disorder, choose “Charcot-Marie-Tooth disease” as your search term in the Rare Disease Database).Friedreich’s ataxia is an autosomal recessive type of hereditary neuromuscular syndrome characterized by slow degenerative changes of the spinal cord, peripheral nerves and the brain. Dysfunction of the central nervous system affects coordination of the muscles in the limbs. Speech can be affected and numbness or weakness of the arms and legs develop. Heart disease (cardiomyopathy) often occurs later in the disease and there is an increased frequency of diabetes. This syndrome appears to be the most common of the many forms of hereditary ataxia. It usually begins during childhood or the teen years. (For more information on this disorder, choose “Ataxia, Friedreich” as your search term in the Rare Disease Database).Ataxia telangiectasia, also known as Louis-Bar syndrome, is inherited as an autosomal recessive trait. It is a progressive cerebellar ataxia that usually begins during infancy. It involves progressive loss of coordination in the limbs, head and eyes with a below-normal immune response to infections. In later stages, dilated blood vessels (telangiectasias) appear in the eyes and skin. Individuals with this form of ataxia are more susceptible to sinus and lung infections, and are at higher risk for developing certain tumors (neoplasms). Ataxia telangiectasia may be misdiagnosed as Friedreich ataxia until dilated blood vessels appear in the skin (telangiectasias). (For more information on this disorder, choose “Ataxia Telangiectasia” as your search term in the Rare Disease Database). | 128 | Autosomal Dominant Hereditary Ataxia |
nord_128_5 | Diagnosis of Autosomal Dominant Hereditary Ataxia | For a diagnosis of hereditary ataxia, there must be a neurological examination that shows poorly coordinated gait, often combined with uncoordinated finger/hand movements. Difficulty with speech (dysarthria) and uncontrolled eye movements (nystagmus) may also be present. In addition, non-genetic causes of ataxia must be excluded. The hereditary nature of the disorder may be established by a positive family history of ataxia or identifying an ataxia-causing gene mutation.Molecular genetic testing is currently available for many hereditary ataxias. To find out whether that is the case for a specific type, speak to your physician or a certified genetic counselor or access the GeneTests website (www.genetests.org). | Diagnosis of Autosomal Dominant Hereditary Ataxia. For a diagnosis of hereditary ataxia, there must be a neurological examination that shows poorly coordinated gait, often combined with uncoordinated finger/hand movements. Difficulty with speech (dysarthria) and uncontrolled eye movements (nystagmus) may also be present. In addition, non-genetic causes of ataxia must be excluded. The hereditary nature of the disorder may be established by a positive family history of ataxia or identifying an ataxia-causing gene mutation.Molecular genetic testing is currently available for many hereditary ataxias. To find out whether that is the case for a specific type, speak to your physician or a certified genetic counselor or access the GeneTests website (www.genetests.org). | 128 | Autosomal Dominant Hereditary Ataxia |
nord_128_6 | Therapies of Autosomal Dominant Hereditary Ataxia | Treatment
Treatment of ataxia is symptomatic and supportive. Continuous medical supervision to avoid potential complications involving the heart, lungs spine, bones and muscles is recommended. Mental functions usually remain unaffected in most forms of hereditary ataxia but emotional strain can affect patients and their families. In such cases, psychological counseling may be helpful.Physical therapy may be recommended by a physician. In addition, various aids may assist muscular movement. Some drugs may be useful in treating some symptoms of ataxia. Propanalol may be effective against static tremors, for instance. Dantrolene, Baclofen, or Tizanidine may help some patients with muscle spasms of the legs. Genetic counseling will be of benefit for patients and families affected by the hereditary ataxias. | Therapies of Autosomal Dominant Hereditary Ataxia. Treatment
Treatment of ataxia is symptomatic and supportive. Continuous medical supervision to avoid potential complications involving the heart, lungs spine, bones and muscles is recommended. Mental functions usually remain unaffected in most forms of hereditary ataxia but emotional strain can affect patients and their families. In such cases, psychological counseling may be helpful.Physical therapy may be recommended by a physician. In addition, various aids may assist muscular movement. Some drugs may be useful in treating some symptoms of ataxia. Propanalol may be effective against static tremors, for instance. Dantrolene, Baclofen, or Tizanidine may help some patients with muscle spasms of the legs. Genetic counseling will be of benefit for patients and families affected by the hereditary ataxias. | 128 | Autosomal Dominant Hereditary Ataxia |
nord_129_0 | Overview of Autosomal Dominant Hyper IgE Syndrome | Autosomal dominant hyper IgE syndrome (AD-HIES) is a rare multisystem primary immunodeficiency disorder. Symptoms often become apparent early during infancy or childhood. The disorder is characterized by repeated bacterial infections of the skin and lungs (pneumonia), skeletal abnormalities, and characteristic facial features. The first symptom is often the development of a dry, red flaky skin rash (eczema) at birth or early during infancy. Researchers have discovered that mutations in the STAT3 gene cause AD-HIES in over 60% of the patients. Most cases of AD-HIES occur as the result of a new mutation in this gene. There are two main forms of hyper IgE syndrome – one inherited in an autosomal dominant pattern and one in an autosomal recessive pattern. Both involve defects of the immune system and elevated levels of immunoglobulin E (hyper IgE) in the blood. For years, researchers considered them different expressions of the same disorder, but now researchers consider them similar, yet distinct disorders. | Overview of Autosomal Dominant Hyper IgE Syndrome. Autosomal dominant hyper IgE syndrome (AD-HIES) is a rare multisystem primary immunodeficiency disorder. Symptoms often become apparent early during infancy or childhood. The disorder is characterized by repeated bacterial infections of the skin and lungs (pneumonia), skeletal abnormalities, and characteristic facial features. The first symptom is often the development of a dry, red flaky skin rash (eczema) at birth or early during infancy. Researchers have discovered that mutations in the STAT3 gene cause AD-HIES in over 60% of the patients. Most cases of AD-HIES occur as the result of a new mutation in this gene. There are two main forms of hyper IgE syndrome – one inherited in an autosomal dominant pattern and one in an autosomal recessive pattern. Both involve defects of the immune system and elevated levels of immunoglobulin E (hyper IgE) in the blood. For years, researchers considered them different expressions of the same disorder, but now researchers consider them similar, yet distinct disorders. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_1 | Symptoms of Autosomal Dominant Hyper IgE Syndrome | The symptoms of AD-HIES may vary greatly from person to person. AD-HIES affects the immune system as well as the development of the skeleton, connective tissue, and teeth. Symptoms may become apparent at birth, during infancy, or during early childhood. In some cases, symptoms may not become apparent until adulthood, and it is not uncommon that the diagnosis is made late. AD-HIES is a rare primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against different infectious agents (i.e., invading microscopic life-forms [microorganisms]). The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g., saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. (The white blood cells [leukocytes] are part of the body’s system of defenses, playing an essential role in protecting against infection as well as fighting infection once it occurs.) In addition, antibodies are produced following vaccination, contributing to protection from infectious diseases like polio, measles, and tetanus. Many individuals with AD-HIES have abnormally high levels of immunoglobulin IgE in the fluid portion of the blood (thus the term hyper IgE). Affected individuals often have somewhat elevated numbers of certain white blood cells known as eosinophils in the body (eosinophilia). The exact reasons for the susceptibility to infection are not understood but a decreased production of the defense proteins interferon gamma and interleukin-17 plays a role. These proteins are important for the attraction and activation of white blood cells to sites of infection. Individuals with AD-HIES are susceptible to recurrent episodes of certain bacterial infections that may affect the skin and lungs. The first symptom of AD-HIES may be a dry, red flaky skin rash (eczema) that develops at birth or early during infancy. Itchiness (pruritis) may also occur. In addition, infants are particularly susceptible to bacterial infection, especially staphylococcal infections. Such infections may cause boils and pus-filled holes (abscesses) to form on the skin. These abscesses are referred to as “cold” abscesses because they lack the surrounding warmth and redness one would expect to accompany such an infection. This can be understood from the fact that few white blood cells are attracted to the site of infection. Abscesses may also be found on the bone behind the ear (mastoid), joints, gums, air passages in the lungs (bronchi), and in the lungs themselves. Affected infants may also have a persistent cough, infection of the sinuses (sinusitis), and recurrent middle ear infections (otitis media). Individuals with AD-HIES develop recurrent lung infections (pneumonia) most often caused by the bacteria Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Pneumonia eventually leads to the development of air-filled cavities within the lungs (pneumatoceles). Pneumatoceles are especially prone to infection with bacteria such as Pseudomonas aeruginosa and especially fungi such as Aspergillus fumigatus. Affected individuals may also be unusually susceptible to opportunistic infections. The term opportunistic infection refers either to infections caused by microorganisms that usually do not cause disease in individuals with fully functioning immune systems or to widespread (systemic) overwhelming disease by microorganisms that typically cause only localized, mild infections. The most common opportunistic infection associated with AD-HIES is an infection caused by the yeast Candida. This is known as mucocutaneous candidiasis, which can affect the mucous membranes of the mouth (oral thrush) or the nail beds (onychomycosis). Mucocutaneous candidiasis can also affect the skin, scalp, and vagina. Additional symptoms may occur in individuals with AD-HIES including skeletal abnormalities and distinctive facial features. Skeletal abnormalities include abnormal side-to-side curvature of the spine (scoliosis), abnormally increased flexibility of certain joints (joint hyperextensibility), progressive thinning and loss of protein of the bones (osteoporosis), and repeated fractures of the long bones of the arms and legs and the ribs. Fractures may occur after minor trauma. Individuals with AD-HIES have characteristic facial features including a broad nasal bridge, deep-set eyes, prominent forehead, and irregularly proportioned cheeks and jaws, and generalized hardening (coarsening) of the skin. Rare facial abnormalities include premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), underdevelopment of one side of the bones in the middle (thoracic) portion of the spinal column (hemivertebrae), and a highly arched palate. Another finding in individuals with AD-HIES is the failure to shed primary (baby) teeth, which, consequently, delays the eruption of permanent teeth or leads to double rows of teeth. Individuals with AD-HIES may also have various eye (ocular) abnormalities including the development of masses or cysts on the eyelid (chalazia), and crossed eyes (strabismus). Some individuals have developed certain cancers (malignancies) suggesting that AD-HIES may be associated with a greater risk of developing malignancy than the general population. The most common cancers associated with AD-HIES are cancers affecting the lymphatic system (lymphomas) such as anaplastic large cell lymphoma and peripheral T-cell lymphoma. | Symptoms of Autosomal Dominant Hyper IgE Syndrome. The symptoms of AD-HIES may vary greatly from person to person. AD-HIES affects the immune system as well as the development of the skeleton, connective tissue, and teeth. Symptoms may become apparent at birth, during infancy, or during early childhood. In some cases, symptoms may not become apparent until adulthood, and it is not uncommon that the diagnosis is made late. AD-HIES is a rare primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against different infectious agents (i.e., invading microscopic life-forms [microorganisms]). The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g., saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. (The white blood cells [leukocytes] are part of the body’s system of defenses, playing an essential role in protecting against infection as well as fighting infection once it occurs.) In addition, antibodies are produced following vaccination, contributing to protection from infectious diseases like polio, measles, and tetanus. Many individuals with AD-HIES have abnormally high levels of immunoglobulin IgE in the fluid portion of the blood (thus the term hyper IgE). Affected individuals often have somewhat elevated numbers of certain white blood cells known as eosinophils in the body (eosinophilia). The exact reasons for the susceptibility to infection are not understood but a decreased production of the defense proteins interferon gamma and interleukin-17 plays a role. These proteins are important for the attraction and activation of white blood cells to sites of infection. Individuals with AD-HIES are susceptible to recurrent episodes of certain bacterial infections that may affect the skin and lungs. The first symptom of AD-HIES may be a dry, red flaky skin rash (eczema) that develops at birth or early during infancy. Itchiness (pruritis) may also occur. In addition, infants are particularly susceptible to bacterial infection, especially staphylococcal infections. Such infections may cause boils and pus-filled holes (abscesses) to form on the skin. These abscesses are referred to as “cold” abscesses because they lack the surrounding warmth and redness one would expect to accompany such an infection. This can be understood from the fact that few white blood cells are attracted to the site of infection. Abscesses may also be found on the bone behind the ear (mastoid), joints, gums, air passages in the lungs (bronchi), and in the lungs themselves. Affected infants may also have a persistent cough, infection of the sinuses (sinusitis), and recurrent middle ear infections (otitis media). Individuals with AD-HIES develop recurrent lung infections (pneumonia) most often caused by the bacteria Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Pneumonia eventually leads to the development of air-filled cavities within the lungs (pneumatoceles). Pneumatoceles are especially prone to infection with bacteria such as Pseudomonas aeruginosa and especially fungi such as Aspergillus fumigatus. Affected individuals may also be unusually susceptible to opportunistic infections. The term opportunistic infection refers either to infections caused by microorganisms that usually do not cause disease in individuals with fully functioning immune systems or to widespread (systemic) overwhelming disease by microorganisms that typically cause only localized, mild infections. The most common opportunistic infection associated with AD-HIES is an infection caused by the yeast Candida. This is known as mucocutaneous candidiasis, which can affect the mucous membranes of the mouth (oral thrush) or the nail beds (onychomycosis). Mucocutaneous candidiasis can also affect the skin, scalp, and vagina. Additional symptoms may occur in individuals with AD-HIES including skeletal abnormalities and distinctive facial features. Skeletal abnormalities include abnormal side-to-side curvature of the spine (scoliosis), abnormally increased flexibility of certain joints (joint hyperextensibility), progressive thinning and loss of protein of the bones (osteoporosis), and repeated fractures of the long bones of the arms and legs and the ribs. Fractures may occur after minor trauma. Individuals with AD-HIES have characteristic facial features including a broad nasal bridge, deep-set eyes, prominent forehead, and irregularly proportioned cheeks and jaws, and generalized hardening (coarsening) of the skin. Rare facial abnormalities include premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), underdevelopment of one side of the bones in the middle (thoracic) portion of the spinal column (hemivertebrae), and a highly arched palate. Another finding in individuals with AD-HIES is the failure to shed primary (baby) teeth, which, consequently, delays the eruption of permanent teeth or leads to double rows of teeth. Individuals with AD-HIES may also have various eye (ocular) abnormalities including the development of masses or cysts on the eyelid (chalazia), and crossed eyes (strabismus). Some individuals have developed certain cancers (malignancies) suggesting that AD-HIES may be associated with a greater risk of developing malignancy than the general population. The most common cancers associated with AD-HIES are cancers affecting the lymphatic system (lymphomas) such as anaplastic large cell lymphoma and peripheral T-cell lymphoma. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_2 | Causes of Autosomal Dominant Hyper IgE Syndrome | Mutations in the STAT3 gene cause AD-HIES. The STAT3 gene is responsible for production of one of the signal transducer and activator of transcription (STAT) proteins that are involved in signaling the immune system to respond to pathogens. The mutations associated with AD-HIES result in a normal amount of STAT3 protein produced but the function of the protein is affected resulting in defective host defense. Mutations in other genes may also be associated with AD-HIES, since STAT3 mutations are found in about 60% of patients.AD-HIES is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Autosomal Dominant Hyper IgE Syndrome. Mutations in the STAT3 gene cause AD-HIES. The STAT3 gene is responsible for production of one of the signal transducer and activator of transcription (STAT) proteins that are involved in signaling the immune system to respond to pathogens. The mutations associated with AD-HIES result in a normal amount of STAT3 protein produced but the function of the protein is affected resulting in defective host defense. Mutations in other genes may also be associated with AD-HIES, since STAT3 mutations are found in about 60% of patients.AD-HIES is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_3 | Affects of Autosomal Dominant Hyper IgE Syndrome | AD-HIES affects males and females in equal numbers and occurs in all ethnic groups. More than 200 cases of hyper IgE syndrome (both the dominant and recessive forms) have been described in the medical literature. However, these disorders may often go unrecognized or misdiagnosed, making it difficult to determine their true frequency in the general population. Although AD-HIES is present during infancy, diagnosis may not be made until adolescence and, in some cases, adulthood. The first case of hyper IgE syndrome was described in the medical literature in 1966. The physicians termed the disorder Job syndrome after the biblical character of Job who was covered in boils and sores over his entire body. | Affects of Autosomal Dominant Hyper IgE Syndrome. AD-HIES affects males and females in equal numbers and occurs in all ethnic groups. More than 200 cases of hyper IgE syndrome (both the dominant and recessive forms) have been described in the medical literature. However, these disorders may often go unrecognized or misdiagnosed, making it difficult to determine their true frequency in the general population. Although AD-HIES is present during infancy, diagnosis may not be made until adolescence and, in some cases, adulthood. The first case of hyper IgE syndrome was described in the medical literature in 1966. The physicians termed the disorder Job syndrome after the biblical character of Job who was covered in boils and sores over his entire body. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_4 | Related disorders of Autosomal Dominant Hyper IgE Syndrome | Symptoms of the following disorders can be similar to those of AD-HIES. Comparisons may be useful for a differential diagnosis. Recently, a clinical disorder closely resembling AD-HIES was described which appeared to be due to an autosomal recessive mode of inheritance of mutations in the ZNF341 gene. ZNF341 was demonstrated to regulate the function of STAT3.Autosomal recessive hyper IgE syndrome (AR-HIES) is a rare primary immunodeficiency disorder. As with AD-HIES, affected individuals are susceptible to bacterial infections of the skin and lungs. Unlike AD-HIES, affected individuals do not have skeletal or connective tissue abnormalities or characteristic facial features, but they are much more likely to develop serious central nervous system and vascular abnormalities. In addition the types of infection that occur also differ as individuals with AR-HIES often develop viral infections (such as severe and recurrent chickenpox and warts). The specific immunological defects associated with the two disorders also differ. AR-HIES more often occurs at a younger age than AD-HIES and is often more severe. AR-HIES is inherited as an autosomal recessive trait. (For more information on this disorder, choose “autosomal recessive hyper-IgE” as your search term in the Rare Disease Database.) Atopic dermatitis is a chronic (long-lasting) disease that affects the skin. Dermatitis means inflammation of the skin. The skin becomes extremely itchy and inflamed causing redness, swelling, cracking, weeping, crusting, and scaling. Atopic dermatitis most often affects infants and young children, but it can continue into adulthood or first show up later in life. In most cases, there are periods of time when the disease is worse, called exacerbations or flares, followed by periods when the skin improves or clears up entirely, called remissions. Many children with atopic dermatitis will experience a permanent remission of the disease when they get older, although their skin often remains dry and easily irritated. Environmental factors can bring on symptoms of atopic dermatitis at any time in the lives of individuals who have inherited the atopic disease trait. Atopic dermatitis is often referred to as eczema, which is a general term for the many types of dermatitis. Atopic dermatitis is the most common of the many types of eczema. The cause of atopic dermatitis is unknown, although malfunction of the immune system plays a role. Of note, the IgE levels in the blood are often elevated in atopic dermatitis (For more information on this disorder, choose “atopic dermatitis” as your search term in the Rare Disease Database.) Wiskott-Aldrich syndrome (WAS) is a rare, inherited disorder of the immune system characterized by recurrent infections due to defects in the immune system (i.e., partial defects in T lymphocyte and B lymphocyte systems, referred to as combined immunodeficiency). In addition, there is a lack of platelets (thrombocytopenia) and these patients suffer from scaly, itchy skin rashes (eczema) that vary in severity among affected individuals. Individuals with WAS carry a high risk of future development of leukemia or lymph node tumors (lymphoma). Because Wiskott-Aldrich syndrome is inherited as an X-linked recessive genetic trait, the disorder is usually fully expressed in males only. However, several reports of WAS affecting females are in the medical literature. (For more information on this disorder, choose “Wiskott-Aldrich” as your search term in the Rare Disease Database.) Netherton syndrome is a rare hereditary disorder characterized by scaling skin, hair anomalies, increased susceptibility to atopic eczema (a skin condition that can result in dry, red and flaky skin), elevated immunoglobulin E (IgE) levels, and other related symptoms. The hair is often fragile and sparse due to a structural defect of the hair shafts that results in a ball-in-socket or bamboo stick-like appearance (trichorrhexis invaginata, “bamboo hair”). Another characteristic associated with some cases is the predisposition to allergies such as asthma, or food allergies that cause skin eruptions. Netherton syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Netherton” as your search term in the Rare Disease Database.) | Related disorders of Autosomal Dominant Hyper IgE Syndrome. Symptoms of the following disorders can be similar to those of AD-HIES. Comparisons may be useful for a differential diagnosis. Recently, a clinical disorder closely resembling AD-HIES was described which appeared to be due to an autosomal recessive mode of inheritance of mutations in the ZNF341 gene. ZNF341 was demonstrated to regulate the function of STAT3.Autosomal recessive hyper IgE syndrome (AR-HIES) is a rare primary immunodeficiency disorder. As with AD-HIES, affected individuals are susceptible to bacterial infections of the skin and lungs. Unlike AD-HIES, affected individuals do not have skeletal or connective tissue abnormalities or characteristic facial features, but they are much more likely to develop serious central nervous system and vascular abnormalities. In addition the types of infection that occur also differ as individuals with AR-HIES often develop viral infections (such as severe and recurrent chickenpox and warts). The specific immunological defects associated with the two disorders also differ. AR-HIES more often occurs at a younger age than AD-HIES and is often more severe. AR-HIES is inherited as an autosomal recessive trait. (For more information on this disorder, choose “autosomal recessive hyper-IgE” as your search term in the Rare Disease Database.) Atopic dermatitis is a chronic (long-lasting) disease that affects the skin. Dermatitis means inflammation of the skin. The skin becomes extremely itchy and inflamed causing redness, swelling, cracking, weeping, crusting, and scaling. Atopic dermatitis most often affects infants and young children, but it can continue into adulthood or first show up later in life. In most cases, there are periods of time when the disease is worse, called exacerbations or flares, followed by periods when the skin improves or clears up entirely, called remissions. Many children with atopic dermatitis will experience a permanent remission of the disease when they get older, although their skin often remains dry and easily irritated. Environmental factors can bring on symptoms of atopic dermatitis at any time in the lives of individuals who have inherited the atopic disease trait. Atopic dermatitis is often referred to as eczema, which is a general term for the many types of dermatitis. Atopic dermatitis is the most common of the many types of eczema. The cause of atopic dermatitis is unknown, although malfunction of the immune system plays a role. Of note, the IgE levels in the blood are often elevated in atopic dermatitis (For more information on this disorder, choose “atopic dermatitis” as your search term in the Rare Disease Database.) Wiskott-Aldrich syndrome (WAS) is a rare, inherited disorder of the immune system characterized by recurrent infections due to defects in the immune system (i.e., partial defects in T lymphocyte and B lymphocyte systems, referred to as combined immunodeficiency). In addition, there is a lack of platelets (thrombocytopenia) and these patients suffer from scaly, itchy skin rashes (eczema) that vary in severity among affected individuals. Individuals with WAS carry a high risk of future development of leukemia or lymph node tumors (lymphoma). Because Wiskott-Aldrich syndrome is inherited as an X-linked recessive genetic trait, the disorder is usually fully expressed in males only. However, several reports of WAS affecting females are in the medical literature. (For more information on this disorder, choose “Wiskott-Aldrich” as your search term in the Rare Disease Database.) Netherton syndrome is a rare hereditary disorder characterized by scaling skin, hair anomalies, increased susceptibility to atopic eczema (a skin condition that can result in dry, red and flaky skin), elevated immunoglobulin E (IgE) levels, and other related symptoms. The hair is often fragile and sparse due to a structural defect of the hair shafts that results in a ball-in-socket or bamboo stick-like appearance (trichorrhexis invaginata, “bamboo hair”). Another characteristic associated with some cases is the predisposition to allergies such as asthma, or food allergies that cause skin eruptions. Netherton syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Netherton” as your search term in the Rare Disease Database.) | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_5 | Diagnosis of Autosomal Dominant Hyper IgE Syndrome | A diagnosis of AD-HIES is made based upon a thorough clinical evaluation, especially a detailed patient history and identification of characteristic findings by a physician with experience with the syndrome. Laboratory studies that may aid in a diagnosis include blood tests that demonstrate elevated levels of IgE in the blood and elevated levels of certain white blood cells known as eosinophils (eosinophilia). IgE levels may drop to normal or near normal levels in adulthood and, therefore, normal IgE levels in an adult do not necessarily rule out a diagnosis of AD-HIES.X-ray studies such as computed tomography (CT scanning) may be used to detect lung infections and the development of pneumatoceles within the lungs. Pneumatoceles are an indicator of AD-HIES. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. A scoring system was devised by researchers at the National Institutes of Health (NIH) to aid in making a diagnosis of AD-HIES. Genetic tests revealing a STAT3 mutation confirms the diagnosis in some 60% of cases. Hence, absence of such mutation does not rule out the diagnosis of AD-HIES. | Diagnosis of Autosomal Dominant Hyper IgE Syndrome. A diagnosis of AD-HIES is made based upon a thorough clinical evaluation, especially a detailed patient history and identification of characteristic findings by a physician with experience with the syndrome. Laboratory studies that may aid in a diagnosis include blood tests that demonstrate elevated levels of IgE in the blood and elevated levels of certain white blood cells known as eosinophils (eosinophilia). IgE levels may drop to normal or near normal levels in adulthood and, therefore, normal IgE levels in an adult do not necessarily rule out a diagnosis of AD-HIES.X-ray studies such as computed tomography (CT scanning) may be used to detect lung infections and the development of pneumatoceles within the lungs. Pneumatoceles are an indicator of AD-HIES. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. A scoring system was devised by researchers at the National Institutes of Health (NIH) to aid in making a diagnosis of AD-HIES. Genetic tests revealing a STAT3 mutation confirms the diagnosis in some 60% of cases. Hence, absence of such mutation does not rule out the diagnosis of AD-HIES. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_129_6 | Therapies of Autosomal Dominant Hyper IgE Syndrome | Treatment
The treatment of AD-HIES is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, internists for adults, dermatologists, dental specialists, immunologists, orthopedists, and other health care professionals may need to systematically and comprehensively plan treatment.The mainstay for treatment of individuals with AD-HIES is preventative (prophylactic) antibiotic therapy against bacterial infection. Common antibiotic medications (e.g., anti-staphylococcal agents) used to treat individuals with AD-HIES include dicloxacillin (flucloxacillin in many European countries) or cotrimoxazole. In severe infections, recombinant interferon-gamma subcutaneously may be given as an adjunctive treatment. Some affected individuals may require therapy for mucocutaneous candidiasis such as fluconazole or itraconazole, which are anti-fungal drugs. Surgical drainage of existing skin lesions, followed by a regimen of antibiotic therapy may be required in some cases. Topical steroids and moisturizing creams may also be used to treat skin lesions. Chronic lung infections may lead to the formation of air cavities (pneumatoceles), which can potentially become infected with Pseudomonas aeruginosa and Aspergillus fumigatus. The drug treatment of these infections can be difficult and management may require surgically opening the chest (thoracotomy) to allow for the removal or drainage of such infected pneumatoceles. Affected individuals may have retained primary teeth removed, be regularly monitored for the development of scoliosis, and be evaluated for fractures following even minor trauma. Scoliosis and fractures may require treatment with various orthopedic procedures. Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Autosomal Dominant Hyper IgE Syndrome. Treatment
The treatment of AD-HIES is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, internists for adults, dermatologists, dental specialists, immunologists, orthopedists, and other health care professionals may need to systematically and comprehensively plan treatment.The mainstay for treatment of individuals with AD-HIES is preventative (prophylactic) antibiotic therapy against bacterial infection. Common antibiotic medications (e.g., anti-staphylococcal agents) used to treat individuals with AD-HIES include dicloxacillin (flucloxacillin in many European countries) or cotrimoxazole. In severe infections, recombinant interferon-gamma subcutaneously may be given as an adjunctive treatment. Some affected individuals may require therapy for mucocutaneous candidiasis such as fluconazole or itraconazole, which are anti-fungal drugs. Surgical drainage of existing skin lesions, followed by a regimen of antibiotic therapy may be required in some cases. Topical steroids and moisturizing creams may also be used to treat skin lesions. Chronic lung infections may lead to the formation of air cavities (pneumatoceles), which can potentially become infected with Pseudomonas aeruginosa and Aspergillus fumigatus. The drug treatment of these infections can be difficult and management may require surgically opening the chest (thoracotomy) to allow for the removal or drainage of such infected pneumatoceles. Affected individuals may have retained primary teeth removed, be regularly monitored for the development of scoliosis, and be evaluated for fractures following even minor trauma. Scoliosis and fractures may require treatment with various orthopedic procedures. Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | 129 | Autosomal Dominant Hyper IgE Syndrome |
nord_130_0 | Overview of Autosomal Dominant Polycystic Kidney Disease | Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. Symptoms caused by cyst formation in the kidneys include high blood pressure (hypertension), pain on the sides of the body between the last rib and the hip (flank pain), blood in the urine (hematuria) and progressively poor function of the kidneys (kidney insufficiency). In most patients, ADPKD eventually progresses to cause end stage renal disease, requiring renal replacement therapy, either dialysis or renal transplantation. ADPKD is not simply a kidney disorder and other organ systems of the body can potentially be affected (multisystem disorder) by the development of cysts. The specific symptoms present in each person depend upon the specific organ systems involved. The liver, pancreas, a membrane covering the spinal cord and brain (arachnoid membrane), the prostate, and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles) may become involved. Abnormalities affecting the heart and blood vessels (cardiovascular system) may also occur in individuals with ADPKD. ADPKD usually does not become apparent until the fourth or fifth decade and was once known as “adult” polycystic kidney disease. However, it has been reported in children and infants. ADPKD is caused by mutations of one of two genes that create certain proteins essential for the proper health of the kidneys and other parts of the body. Approximately 85 % have ADPKD1, the most aggressive form of the disease; those with ADPKD2 progress to kidney insufficiency about 20 years later. | Overview of Autosomal Dominant Polycystic Kidney Disease. Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. Symptoms caused by cyst formation in the kidneys include high blood pressure (hypertension), pain on the sides of the body between the last rib and the hip (flank pain), blood in the urine (hematuria) and progressively poor function of the kidneys (kidney insufficiency). In most patients, ADPKD eventually progresses to cause end stage renal disease, requiring renal replacement therapy, either dialysis or renal transplantation. ADPKD is not simply a kidney disorder and other organ systems of the body can potentially be affected (multisystem disorder) by the development of cysts. The specific symptoms present in each person depend upon the specific organ systems involved. The liver, pancreas, a membrane covering the spinal cord and brain (arachnoid membrane), the prostate, and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles) may become involved. Abnormalities affecting the heart and blood vessels (cardiovascular system) may also occur in individuals with ADPKD. ADPKD usually does not become apparent until the fourth or fifth decade and was once known as “adult” polycystic kidney disease. However, it has been reported in children and infants. ADPKD is caused by mutations of one of two genes that create certain proteins essential for the proper health of the kidneys and other parts of the body. Approximately 85 % have ADPKD1, the most aggressive form of the disease; those with ADPKD2 progress to kidney insufficiency about 20 years later. | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_1 | Symptoms of Autosomal Dominant Polycystic Kidney Disease | The specific symptoms and their severity can vary greatly from one person to another, even among members of the same family. Most affected individuals develop symptoms between the third and fifth decades of life. However, symptoms may occur during childhood or even in infancy. Some affected individuals never develop obvious symptoms (asymptomatic) and may be diagnosed with ADPKD incidentally in the eighth or ninth decade of life. ADPKD is a highly variable, multisystem disorder; it is important to note that affected individuals will not have all of the symptoms discussed below.KIDNEY (RENAL) DISEASE
The characteristic finding of ADPKD is the development of fluid-filled sacs (cysts) in the kidneys. All individuals with ADPKD develop cysts in the kidneys, but the number, size, progression and severity of cyst development varies greatly from one person to another. In most cases, renal cysts continue to grow and multiply, potentially causing a variety of symptoms including abnormal enlargement of the kidneys, high blood pressure (hypertension), flank pain, hematuria, poor function of the kidneys (renal insufficiency) and, potentially, kidney failure.Hypertension affects approximately 50 percent of individuals aged 20-34 most of whom have normal kidney function. In some cases, hypertension may be the first symptom noted. Hypertension usually occurs long before the development of renal failure. Nearly all individuals who develop renal failure have hypertension.Pain is the most commonly reported symptom of ADPKD. Pain may be described as a sense or feeling of fullness or chronic pain affecting the “flank,” the area of the body between the last rib and the hip (i.e., where the kidneys are located). In some cases, pain may be severe (acute) due to bleeding (hemorrhaging) complications, the passage of kidney stones or chronic urinary tract infection.Eventually, affected individuals may develop renal insufficiency, which refers to the impaired ability of the kidneys to perform their basic functions. The kidneys are two bean-shaped organs located under the ribcage. The kidneys have several functions including filtering and excreting waste products from the blood and body, creating certain hormones, and helping maintain the balance of certain chemicals in the body such as potassium, sodium, chloride calcium and other electrolytes. Damage to the kidneys in ADPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, nausea and vomiting and nocturia (night-time urination) (due to decreased urinary concentration).The progression to end stage renal disease is slowly progressive in most cases. End stage renal disease is when the kidneys can no longer function properly; they will not be able to filter waste products, regulate hormones or electrolytes, or concentrate urine sufficiently to maintain life. Approximately 50 percent of individuals with the ADPKD1 type develop end stage renal disease by 53 years of age. Those with the ADPKD2 type develop kidney failure about 20 years later.. A wide variety of symptoms may be associated with end stage renal disease including fatigue, weakness, weight loss, difficulty breathing, nausea, vomiting, and cognitive problems such as difficulties concentrating or thinking clearly.Additional symptoms that can occur in individuals with ADPKD include blood in the urine (hematuria), abdominal or lower back pain, the development of kidney stones (nephrolithiasis), chronic urinary traction infections, and cyst infections. Hematuria affects approximately 40 percent of individuals. Significant (gross) hematuria before the age of 30 is associated with an increased risk of progression of kidney disease. Kidney stones affect approximately 20 percent of individuals with ADPKD. Cyst infections are associated with fever and back or abdominal pain.EXTRARENAL DISEASE
Individuals with ADPKD may have symptoms caused by problems outside the kidneys (extrarenal disease). For example, affected individuals may develop cysts in other organs of the body especially the liver (polycystic liver disease). The frequency of polycystic liver disease increases with age affecting more than 90 % of patients with ADPKD1 or ADPKD2. Liver cysts usually develop much later in life and progress much slower than kidney cysts. Women tend to have more liver cysts and larger livers than men. In most cases polycystic liver disease does not cause symptoms. Symptoms that can occur include enlargement of the liver (hepatomegaly), pain in the lower portion of the back, an abnormal early feeling of fullness (early satiety), shortness of breath especially upon exertion (dyspnea), and backflow of the contents of the stomach into the esophagus (gastroesophageal reflux). Yellowing of the eyes and the skin (jaundice) occur rarely if cysts block the bile ducts.Other organs that may be affected by the formation of cysts include the pancreas, arachnoid membrane (a layer of tissue in the brain), and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles). Cysts affecting the pancreas usually do not cause symptoms except in rare cases in which inflammation of the pancreas (pancreatitis) occurs. Cysts affecting the arachnoid membrane usually do not cause symptoms, but may increase the risk of developing a collection of blood between the outer and middle layers of the covering (meninges) of the brain (subdural hematoma). Cysts affecting the seminal vesicles can potentially cause infertility.ADPKD can also potentially affect the heart and blood vessels (cardiovascular system). Involvement of the valves of the heart can cause mitral valve prolapse. The mitral valve is located between the left upper and left lower chambers (left atrium and left ventricle) of the heart. Mitral valve prolapse occurs when one or both of the flaps (cusps) of the mitral valve bulge or collapse backward (prolapse) into the left upper chamber (atrium) of the heart. In some cases, this may allow leakage or the backward flow of blood from the left lower chamber of the heart (ventricle) back into the left atrium (mitral regurgitation). In some cases, no associated symptoms are apparent (asymptomatic). However, in other cases, mitral valve prolapse can result in chest pain, abnormal heart rhythms (arrhythmias), fatigue, dizziness, and/or other symptoms and signs.Some individuals with ADPKD may develop a thickening of the walls the heart, especially within the left ventricle (ventricular hypertrophy). The left ventricle is the lower left chamber of the heart through which oxygenated blood passes into the main artery of the body (aorta). Left ventricular hypertrophy can obstruct the flow of blood from the heart and can be associated with a variety of symptoms.Some affected individuals may develop widening (dilatation) of the part of the aorta (the main artery of the body) that is attached to the heart (aortic root). Aortic root dilatation can cause aortic insufficiency, in which the valves of the aorta weaken or balloon allowing blood to flow backward into the left ventricle. This can cause a rising pulse rate, chest pain, fatigue, palpitations, shortness of breath and fainting. In rare cases, some individuals with ADPKD have developed an aortic dissection, a life-threatening condition in which there is a tear within the middle layer of the wall of the aorta. This tear causes the middle layer to separate (dissect) from the inner layer.Another potentially serious complication of ADPKD is the development of weak areas in the walls of the blood vessels of the brain (intracranial aneurysm). Intracranial aneurysms can cause paralysis (palsy) of certain cranial nerves and seizures due to compression of nearby brain structures. If aneurysms rupture they can cause life-threatening bleeding complications. Intracranial aneurysms tend to cluster within families; they occur in approximately 16 percent of individuals with ADPKD with a positive family history of aneurysms. Intracranial aneurysms occur in approximately 6 percent of individuals with ADPKD with a negative family history of aneurysms.Patients frequently have weaknesses in the abdominal wall near the midline (ventral hernia), in the wall of the abdomen near the bellybutton (umbilical hernia) or protrusion of part of the intestines through a tear in the wall of the lower abdomen (inguinal hernia).Some individuals with ADPKD may develop out-pouches diverticula on the walls of the large intestines (colon). Inflammation within these may cause abdominal pain, changes in bowel movements (e.g., diarrhea or constipation) and bleeding from part of the large intestines via the rectum. | Symptoms of Autosomal Dominant Polycystic Kidney Disease. The specific symptoms and their severity can vary greatly from one person to another, even among members of the same family. Most affected individuals develop symptoms between the third and fifth decades of life. However, symptoms may occur during childhood or even in infancy. Some affected individuals never develop obvious symptoms (asymptomatic) and may be diagnosed with ADPKD incidentally in the eighth or ninth decade of life. ADPKD is a highly variable, multisystem disorder; it is important to note that affected individuals will not have all of the symptoms discussed below.KIDNEY (RENAL) DISEASE
The characteristic finding of ADPKD is the development of fluid-filled sacs (cysts) in the kidneys. All individuals with ADPKD develop cysts in the kidneys, but the number, size, progression and severity of cyst development varies greatly from one person to another. In most cases, renal cysts continue to grow and multiply, potentially causing a variety of symptoms including abnormal enlargement of the kidneys, high blood pressure (hypertension), flank pain, hematuria, poor function of the kidneys (renal insufficiency) and, potentially, kidney failure.Hypertension affects approximately 50 percent of individuals aged 20-34 most of whom have normal kidney function. In some cases, hypertension may be the first symptom noted. Hypertension usually occurs long before the development of renal failure. Nearly all individuals who develop renal failure have hypertension.Pain is the most commonly reported symptom of ADPKD. Pain may be described as a sense or feeling of fullness or chronic pain affecting the “flank,” the area of the body between the last rib and the hip (i.e., where the kidneys are located). In some cases, pain may be severe (acute) due to bleeding (hemorrhaging) complications, the passage of kidney stones or chronic urinary tract infection.Eventually, affected individuals may develop renal insufficiency, which refers to the impaired ability of the kidneys to perform their basic functions. The kidneys are two bean-shaped organs located under the ribcage. The kidneys have several functions including filtering and excreting waste products from the blood and body, creating certain hormones, and helping maintain the balance of certain chemicals in the body such as potassium, sodium, chloride calcium and other electrolytes. Damage to the kidneys in ADPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, nausea and vomiting and nocturia (night-time urination) (due to decreased urinary concentration).The progression to end stage renal disease is slowly progressive in most cases. End stage renal disease is when the kidneys can no longer function properly; they will not be able to filter waste products, regulate hormones or electrolytes, or concentrate urine sufficiently to maintain life. Approximately 50 percent of individuals with the ADPKD1 type develop end stage renal disease by 53 years of age. Those with the ADPKD2 type develop kidney failure about 20 years later.. A wide variety of symptoms may be associated with end stage renal disease including fatigue, weakness, weight loss, difficulty breathing, nausea, vomiting, and cognitive problems such as difficulties concentrating or thinking clearly.Additional symptoms that can occur in individuals with ADPKD include blood in the urine (hematuria), abdominal or lower back pain, the development of kidney stones (nephrolithiasis), chronic urinary traction infections, and cyst infections. Hematuria affects approximately 40 percent of individuals. Significant (gross) hematuria before the age of 30 is associated with an increased risk of progression of kidney disease. Kidney stones affect approximately 20 percent of individuals with ADPKD. Cyst infections are associated with fever and back or abdominal pain.EXTRARENAL DISEASE
Individuals with ADPKD may have symptoms caused by problems outside the kidneys (extrarenal disease). For example, affected individuals may develop cysts in other organs of the body especially the liver (polycystic liver disease). The frequency of polycystic liver disease increases with age affecting more than 90 % of patients with ADPKD1 or ADPKD2. Liver cysts usually develop much later in life and progress much slower than kidney cysts. Women tend to have more liver cysts and larger livers than men. In most cases polycystic liver disease does not cause symptoms. Symptoms that can occur include enlargement of the liver (hepatomegaly), pain in the lower portion of the back, an abnormal early feeling of fullness (early satiety), shortness of breath especially upon exertion (dyspnea), and backflow of the contents of the stomach into the esophagus (gastroesophageal reflux). Yellowing of the eyes and the skin (jaundice) occur rarely if cysts block the bile ducts.Other organs that may be affected by the formation of cysts include the pancreas, arachnoid membrane (a layer of tissue in the brain), and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles). Cysts affecting the pancreas usually do not cause symptoms except in rare cases in which inflammation of the pancreas (pancreatitis) occurs. Cysts affecting the arachnoid membrane usually do not cause symptoms, but may increase the risk of developing a collection of blood between the outer and middle layers of the covering (meninges) of the brain (subdural hematoma). Cysts affecting the seminal vesicles can potentially cause infertility.ADPKD can also potentially affect the heart and blood vessels (cardiovascular system). Involvement of the valves of the heart can cause mitral valve prolapse. The mitral valve is located between the left upper and left lower chambers (left atrium and left ventricle) of the heart. Mitral valve prolapse occurs when one or both of the flaps (cusps) of the mitral valve bulge or collapse backward (prolapse) into the left upper chamber (atrium) of the heart. In some cases, this may allow leakage or the backward flow of blood from the left lower chamber of the heart (ventricle) back into the left atrium (mitral regurgitation). In some cases, no associated symptoms are apparent (asymptomatic). However, in other cases, mitral valve prolapse can result in chest pain, abnormal heart rhythms (arrhythmias), fatigue, dizziness, and/or other symptoms and signs.Some individuals with ADPKD may develop a thickening of the walls the heart, especially within the left ventricle (ventricular hypertrophy). The left ventricle is the lower left chamber of the heart through which oxygenated blood passes into the main artery of the body (aorta). Left ventricular hypertrophy can obstruct the flow of blood from the heart and can be associated with a variety of symptoms.Some affected individuals may develop widening (dilatation) of the part of the aorta (the main artery of the body) that is attached to the heart (aortic root). Aortic root dilatation can cause aortic insufficiency, in which the valves of the aorta weaken or balloon allowing blood to flow backward into the left ventricle. This can cause a rising pulse rate, chest pain, fatigue, palpitations, shortness of breath and fainting. In rare cases, some individuals with ADPKD have developed an aortic dissection, a life-threatening condition in which there is a tear within the middle layer of the wall of the aorta. This tear causes the middle layer to separate (dissect) from the inner layer.Another potentially serious complication of ADPKD is the development of weak areas in the walls of the blood vessels of the brain (intracranial aneurysm). Intracranial aneurysms can cause paralysis (palsy) of certain cranial nerves and seizures due to compression of nearby brain structures. If aneurysms rupture they can cause life-threatening bleeding complications. Intracranial aneurysms tend to cluster within families; they occur in approximately 16 percent of individuals with ADPKD with a positive family history of aneurysms. Intracranial aneurysms occur in approximately 6 percent of individuals with ADPKD with a negative family history of aneurysms.Patients frequently have weaknesses in the abdominal wall near the midline (ventral hernia), in the wall of the abdomen near the bellybutton (umbilical hernia) or protrusion of part of the intestines through a tear in the wall of the lower abdomen (inguinal hernia).Some individuals with ADPKD may develop out-pouches diverticula on the walls of the large intestines (colon). Inflammation within these may cause abdominal pain, changes in bowel movements (e.g., diarrhea or constipation) and bleeding from part of the large intestines via the rectum. | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_2 | Causes of Autosomal Dominant Polycystic Kidney Disease | ADPKD is caused by mutations of one of two genes, the ADPKD1 gene or the ADPKD2 gene. Mutations of the ADPKD1 gene account for approximately 85 percent of cases; the ADPKD2 gene accounts for approximately 15 percent of cases. These mutations are inherited as an autosomal dominant trait. In approximately 10 percent of cases, the mutation occurs randomly for no apparent reason (sporadically). Mutations of the ADPKD1 gene are generally associated with more severe disease, earlier age of onset and early age of onset of end stage renal disease.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.Researchers believe that additional factors influence the severity of ADPKD including modifier genes and environmental factors. Modifier genes, unlike the genes that cause ADPKD, affect the clinical severity of the disorder. Modifier genes and environmental factors contribute to the wide variability in the severity of ADPKD in affected individuals.Investigators have determined that the ADPKD1 gene is located on the short arm (p) on chromosome 16 (16p13.3) and that the ADPKD2 gene is located on the long arm (q) of chromosome 4 (4q21). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 16p13.3” refers to band 13.3 on the short arm of chromosome 16. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The ADPKD1 gene contains instructions for creating (encoding) a protein known as polycystin-1; the ADPKD2 gene encodes a protein known as polycystin-2. The exact roles that these proteins play in the proper function and health of the body are not fully understood. These proteins most likely have multiple functions. Researchers speculate that these proteins are involved in regulating the development of tubes and blood vessels in the kidneys and other organs and also help to increase the flow of calcium through cell membranes.The symptoms of ADPKD result from the development and continued enlargement of cysts in the kidneys and other organ systems of the body. Cysts within the kidneys form in the walls of hair-sized structures called nephrons, which are small tubules that serve as the basic filtering units of the kidneys and help remove waste from the blood. Cysts form on the walls of nephrons and resemble blisters. Most cysts eventually separate from the nephron and continue to grow as isolated sacs of fluid. Cysts grow like tumors to cause the kidneys to become abnormally large. Kidney cysts in ADPKD can potentially number in the thousands and range in size from pin-head to larger than a grapefruit. | Causes of Autosomal Dominant Polycystic Kidney Disease. ADPKD is caused by mutations of one of two genes, the ADPKD1 gene or the ADPKD2 gene. Mutations of the ADPKD1 gene account for approximately 85 percent of cases; the ADPKD2 gene accounts for approximately 15 percent of cases. These mutations are inherited as an autosomal dominant trait. In approximately 10 percent of cases, the mutation occurs randomly for no apparent reason (sporadically). Mutations of the ADPKD1 gene are generally associated with more severe disease, earlier age of onset and early age of onset of end stage renal disease.Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.Researchers believe that additional factors influence the severity of ADPKD including modifier genes and environmental factors. Modifier genes, unlike the genes that cause ADPKD, affect the clinical severity of the disorder. Modifier genes and environmental factors contribute to the wide variability in the severity of ADPKD in affected individuals.Investigators have determined that the ADPKD1 gene is located on the short arm (p) on chromosome 16 (16p13.3) and that the ADPKD2 gene is located on the long arm (q) of chromosome 4 (4q21). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 16p13.3” refers to band 13.3 on the short arm of chromosome 16. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The ADPKD1 gene contains instructions for creating (encoding) a protein known as polycystin-1; the ADPKD2 gene encodes a protein known as polycystin-2. The exact roles that these proteins play in the proper function and health of the body are not fully understood. These proteins most likely have multiple functions. Researchers speculate that these proteins are involved in regulating the development of tubes and blood vessels in the kidneys and other organs and also help to increase the flow of calcium through cell membranes.The symptoms of ADPKD result from the development and continued enlargement of cysts in the kidneys and other organ systems of the body. Cysts within the kidneys form in the walls of hair-sized structures called nephrons, which are small tubules that serve as the basic filtering units of the kidneys and help remove waste from the blood. Cysts form on the walls of nephrons and resemble blisters. Most cysts eventually separate from the nephron and continue to grow as isolated sacs of fluid. Cysts grow like tumors to cause the kidneys to become abnormally large. Kidney cysts in ADPKD can potentially number in the thousands and range in size from pin-head to larger than a grapefruit. | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_3 | Affects of Autosomal Dominant Polycystic Kidney Disease | ADPKD affects males and females in equal numbers. Although a head-count has never been done, autopsy records show that between 1 in 400-1,000 people in the general population had ADPKD. There are approximately 6,000 new cases diagnosed each year in the United States. Approximately 6-10 percent of individuals receiving dialysis and renal transplant treatments in the United States have ADPKD. ADPKD is estimated to affect approximately 200,000 to 600,000 in the United States and another 12,000,000 people million worldwide, but only about one-fourth may know they have the disease. | Affects of Autosomal Dominant Polycystic Kidney Disease. ADPKD affects males and females in equal numbers. Although a head-count has never been done, autopsy records show that between 1 in 400-1,000 people in the general population had ADPKD. There are approximately 6,000 new cases diagnosed each year in the United States. Approximately 6-10 percent of individuals receiving dialysis and renal transplant treatments in the United States have ADPKD. ADPKD is estimated to affect approximately 200,000 to 600,000 in the United States and another 12,000,000 people million worldwide, but only about one-fourth may know they have the disease. | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_4 | Related disorders of Autosomal Dominant Polycystic Kidney Disease | Symptoms of the following disorders can be similar to those of ADPKD. Comparisons may be useful for a differential diagnosis.Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the formation of fluid-filled sacs (cysts) in the kidneys. The severity of the disorder and the specific symptoms can vary greatly from one person to another. Most affected infants have enlarged kidneys during the newborn (neonatal) period. A variety of liver abnormalities and incomplete development of the lungs (pulmonary hypoplasia) may also be present. Breathing (respiratory) abnormalities, frequent urination, and feeding difficulties may also occur. More than 50 percent of affected children develop end stage renal disease sometime during the first decade of life. In some cases, symptoms do not develop until adolescence. ARPKD is caused by mutations of the PHKD1 gene. (For more information on this disorder, choose “autosomal recessive polycystic kidney disease” as your search term in the Rare Disease Database.)Tuberous sclerosis is a rare genetic multisystem disorder that is typically apparent shortly after birth. The disorder may be characterized by episodes of uncontrolled electrical activity in the brain (seizures); mental retardation; distinctive skin abnormalities (lesions); and benign (noncancerous), tumor-like nodules (hamartomas) of the brain, certain regions of the eyes (e.g., retinas), the heart, the kidneys, the lungs, or other tissues or organs. In addition, many affected individuals may have cyst-like areas within certain skeletal regions, particularly bones of the fingers and toes (phalanges). Characteristic skin lesions include sharply defined areas of decreased skin coloration (hypopigmentation) that may develop during infancy and relatively small reddish nodules that may appear on the cheeks and nose beginning at approximately age four. These reddish lesions eventually enlarge, blend together (coalesce), and develop a wart-like appearance (sebaceous adenomas). Additional skin lesions may also develop, including flat, “coffee-colored” areas of increased skin pigmentation (café-au-lait spots); benign, fibrous nodules (fibromas) arising around or beneath the nails; or rough, elevated, “knobby” lesions (shagreen patches) on the lower back. Tuberous sclerosis results from changes (mutations) in a gene or genes that may occur spontaneously (sporadically) for unknown reasons or be inherited as an autosomal dominant trait. Most cases represent new (sporadic) gene mutations, with no family history of the disease. Mutations of at least two different genes are known to cause tuberous sclerosis. One gene (TSC1) has been mapped to the long arm (q) of chromosome 9 (9q34). A second gene for the disease (TSC2) is located on the short arm (p) of chromosome 16 (16p13.3). (For more information on this disorder, choose “tuberous sclerosis” as your search term in the Rare Disease Database.)Von Hippel-Lindau syndrome (VHL) is an autosomal dominant genetic disorder characterized by the abnormal growth of blood vessels in certain parts of the body (angiomatosis). Very small blood vessels (capillaries) “knot” together to form benign growths known as angiomas or hemangioblastomas. These may develop in the retinas of the eyes (retinal hemangioblastomas) or in the brain or spinal cord, or in the inner ear (endolymphatic sac tumors). Vascular tumors may also occur in the kidneys (renal cell carcinoma), pancreas (cysts or pancreatic neuroendocrine tumors) and/or adrenal glands (pheochromocytoma). The symptoms of von Hippel-Lindau vary greatly and depend on the size and location of the growths. (For more information on this disorder, choose “von Hippel-Lindau” as your search term in the Rare Disease Database.) | Related disorders of Autosomal Dominant Polycystic Kidney Disease. Symptoms of the following disorders can be similar to those of ADPKD. Comparisons may be useful for a differential diagnosis.Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the formation of fluid-filled sacs (cysts) in the kidneys. The severity of the disorder and the specific symptoms can vary greatly from one person to another. Most affected infants have enlarged kidneys during the newborn (neonatal) period. A variety of liver abnormalities and incomplete development of the lungs (pulmonary hypoplasia) may also be present. Breathing (respiratory) abnormalities, frequent urination, and feeding difficulties may also occur. More than 50 percent of affected children develop end stage renal disease sometime during the first decade of life. In some cases, symptoms do not develop until adolescence. ARPKD is caused by mutations of the PHKD1 gene. (For more information on this disorder, choose “autosomal recessive polycystic kidney disease” as your search term in the Rare Disease Database.)Tuberous sclerosis is a rare genetic multisystem disorder that is typically apparent shortly after birth. The disorder may be characterized by episodes of uncontrolled electrical activity in the brain (seizures); mental retardation; distinctive skin abnormalities (lesions); and benign (noncancerous), tumor-like nodules (hamartomas) of the brain, certain regions of the eyes (e.g., retinas), the heart, the kidneys, the lungs, or other tissues or organs. In addition, many affected individuals may have cyst-like areas within certain skeletal regions, particularly bones of the fingers and toes (phalanges). Characteristic skin lesions include sharply defined areas of decreased skin coloration (hypopigmentation) that may develop during infancy and relatively small reddish nodules that may appear on the cheeks and nose beginning at approximately age four. These reddish lesions eventually enlarge, blend together (coalesce), and develop a wart-like appearance (sebaceous adenomas). Additional skin lesions may also develop, including flat, “coffee-colored” areas of increased skin pigmentation (café-au-lait spots); benign, fibrous nodules (fibromas) arising around or beneath the nails; or rough, elevated, “knobby” lesions (shagreen patches) on the lower back. Tuberous sclerosis results from changes (mutations) in a gene or genes that may occur spontaneously (sporadically) for unknown reasons or be inherited as an autosomal dominant trait. Most cases represent new (sporadic) gene mutations, with no family history of the disease. Mutations of at least two different genes are known to cause tuberous sclerosis. One gene (TSC1) has been mapped to the long arm (q) of chromosome 9 (9q34). A second gene for the disease (TSC2) is located on the short arm (p) of chromosome 16 (16p13.3). (For more information on this disorder, choose “tuberous sclerosis” as your search term in the Rare Disease Database.)Von Hippel-Lindau syndrome (VHL) is an autosomal dominant genetic disorder characterized by the abnormal growth of blood vessels in certain parts of the body (angiomatosis). Very small blood vessels (capillaries) “knot” together to form benign growths known as angiomas or hemangioblastomas. These may develop in the retinas of the eyes (retinal hemangioblastomas) or in the brain or spinal cord, or in the inner ear (endolymphatic sac tumors). Vascular tumors may also occur in the kidneys (renal cell carcinoma), pancreas (cysts or pancreatic neuroendocrine tumors) and/or adrenal glands (pheochromocytoma). The symptoms of von Hippel-Lindau vary greatly and depend on the size and location of the growths. (For more information on this disorder, choose “von Hippel-Lindau” as your search term in the Rare Disease Database.) | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_5 | Diagnosis of Autosomal Dominant Polycystic Kidney Disease | ADPKD is diagnosed by a thorough clinical evaluation, a complete patient and family history, and imaging techniques, such as ultrasonography, computed tomography and magnetic resonance imaging. Such imaging studies are typically conducted for individuals with symptoms suggestive of ADPKD; in addition, they may be recommended as screening procedures for relatives of those diagnosed with ADPKD. Ultrasonography is a diagnostic study in which reflected echoes of high-frequency sound waves create an image of certain internal organs such as the kidneys. In some affected individuals, additional imaging studies, such as computerized tomography (CT) and magnetic resonance (MR) imaging, may also be recommended to help detect small cysts and determine the full extent of the disorder. During CT scanning, a computer and x-rays are used to create cross-sectional images of certain tissue structures.As discussed, ADPKD usually causes symptoms beginning during adulthood. However, in some cases, it may be detected in childhood or infancy or even before birth (prenatally) with ultrasonography. During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus within the uterus.Molecular genetic testing for mutations in the ADPKD1 and ADPKD2 genes is available to confirm the diagnosis.As noted earlier, in individuals with ADPKD, there is a potential risk of bleeding (intracranial hemorrhaging) within the brain. It is advisable that people with a family history of intracranial hemorrhaging or with headaches undergo appropriate screening tests (e.g., magnetic resonance angiography [MRA], CT scanning). | Diagnosis of Autosomal Dominant Polycystic Kidney Disease. ADPKD is diagnosed by a thorough clinical evaluation, a complete patient and family history, and imaging techniques, such as ultrasonography, computed tomography and magnetic resonance imaging. Such imaging studies are typically conducted for individuals with symptoms suggestive of ADPKD; in addition, they may be recommended as screening procedures for relatives of those diagnosed with ADPKD. Ultrasonography is a diagnostic study in which reflected echoes of high-frequency sound waves create an image of certain internal organs such as the kidneys. In some affected individuals, additional imaging studies, such as computerized tomography (CT) and magnetic resonance (MR) imaging, may also be recommended to help detect small cysts and determine the full extent of the disorder. During CT scanning, a computer and x-rays are used to create cross-sectional images of certain tissue structures.As discussed, ADPKD usually causes symptoms beginning during adulthood. However, in some cases, it may be detected in childhood or infancy or even before birth (prenatally) with ultrasonography. During fetal ultrasonography, reflected sound waves are used to create an image of the developing fetus within the uterus.Molecular genetic testing for mutations in the ADPKD1 and ADPKD2 genes is available to confirm the diagnosis.As noted earlier, in individuals with ADPKD, there is a potential risk of bleeding (intracranial hemorrhaging) within the brain. It is advisable that people with a family history of intracranial hemorrhaging or with headaches undergo appropriate screening tests (e.g., magnetic resonance angiography [MRA], CT scanning). | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_130_6 | Therapies of Autosomal Dominant Polycystic Kidney Disease | Treatment
The treatment of individuals with ADPKD involves detailed attention to diet, fluid intake, blood pressure control and the avoidance of harmful drug and life-style choices. Implementation of these measures early in the course of the disease should slow the progression of kidney (renal) disease and preserve kidney function to some extent. . Effective treatment requires the coordinated efforts of a team of specialists working together to systematically and comprehensively plan an affected individual's personal prescription. Such specialists may include primary care family physicians, pediatricians or internists who collaborate with physicians specializing in disorders of the kidneys (nephrologists), surgical disorders of the urinary tract (urologists), dietitians, and/or other health care professionals. Genetic counseling may be of benefit for affected individuals and their families.Hypertension
In individuals with ADPKD, therapy typically includes aggressive treatment of high blood pressure (hypertension). Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) are preferred by most specialists who treat hypertension in ADPKD patients. These drugs block substances known to cause the hypertension by narrowing blood vessels (constrict) within the cystic kidneys. In individuals with ADPKD, these drugs may be more effective in preserving kidney function and preventing left ventricular hypertrophy than other therapies for hypertension.Pain
Pain associated with ADPKD can be treated in several ways. Acute pain associated with the rupture of a cyst into adjacent kidney tissue or into the urine collecting system can usually be treated with additional fluid intake, bed rest, and analgesics. Acute pain caused by infections, kidney stones, or a tumor will require an intervention study to be ruled out. Individuals with chronic, mild pain may be able to control it with over-the-counter medications containing acetaminophen. Long-term use of drugs that are toxic to the kidneys such as combination analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided. For more disabling pain, tricyclic antidepressant drugs or narcotics may be necessary. Splanchic nerve blockade, a procedure in which the injection of local anesthesia or steroids into certain nerves provides temporary relief of pain and ablation of nerves to the kidneys may give some relief. In rare cases a catastrophic decline in the quality of life may necessitate percutaneous cyst decompression, surgical incision and drainage of cysts, or even nephrectomy.Lifestyle Modification
Research has indicated that certain lifestyle modifications may be beneficial for some individuals with ADPKD. Although no specific diet is proven to ameliorate disease progression, some physicians recommend that individuals with ADPKD avoid foods and drinks containing caffeine, limit the amount of protein they eat, and reduce the amount of salt in their diets. Diets should be enriched in fruits and vegetables to provide sufficient potassium and reduce the intake of acid-forming foods. Affected individuals are also encouraged to exercise as much as they are able, to not smoke and to drink extra water throughout the day. Adults are advised to drink 3 liters (quarts) per day and children proportionately less.Cyst Complications
In some cases, as cysts grow larger they cause obstruction or compression of nearby structures such as organs or blood vessels. In these cases, surgery may be necessary to drain cysts. Cysts can also rupture causing bleeding (hemorrhaging) or become infected. Cyst hemorrhaging usually responds to bed rest, certain painkillers (analgesics), and fluid intake (hydration) to prevent the formation of obstructing blood clots.Cyst infections may be difficult to treat and require aggressive antibiotic therapy. However, because antibiotics have difficulty penetrating cysts, this therapy is not always effective. Lipophilic antibiotics (floxacin derivatives) are most effective in troublesome infections. When infected cysts do not respond to antibiotic therapy, surgery to drain the cysts may be necessary.Kidney Stones (Nephrolithiasis)
Individuals with ADPKD should drink plenty of water as a preventive (prophylactic) measure against the formation of kidney stones. Individuals with chronic stone formation should take in 3-4 liters of water and potassium citrate. In some cases, extracorporeal shock-wave lithotripsy (in which shock waves are used to break apart kidney stones) or percutaneous nephrostolithotomy (in which a needle is passed through the skin into the kidney to remove small stones) may be used to treat affected individuals.Urinary Tract Infections
Chronic urinary tract infections or kidney infections should be promptly treated with antibiotics to prevent the spread of infection to cysts within the kidneys, which is much more difficult to treat. Women with ADPKD are more susceptible to developing urinary tract infections than men.Polycystic Liver Disease
In most cases, polycystic liver disease does not require treatment. When polycystic liver disease causes symptoms, affected individuals may be advised to avoid caffeine and estrogens (e.g., hormone replacement therapy). In women who require hormone replacement therapy, transdermal preparations avoid sending high concentrations of drug to the liver as occurs when they are taken by mouth. Certain medications such as proton pump inhibitors, which reduce acids level in the stomach, or H2 blockers may be used to provide relief from gastro-esophageal reflux disease (GERD).In severe cases, certain procedures may be required to reduce the number of cysts and the size of the liver. Such procedures include percutaneous cyst aspiration, in which a needle is passed through the skin to drain fluid from a cyst; laparoscopic cyst fenestration, in which a small incision is made in the abdominal wall allowing a surgeon to cut a hole into the cyst through which the fluid to drains into the abdominal cavity; and surgical removal (resection) of part of the liver along with cyst fenestration. In rare cases, a liver transplant may be required. The specific procedure used depends on several factors including the progression of the disease, the size, number and location of the cysts, an individual’s age and general health, and other elements.In some cases, liver cysts may become infected. Treatment with lipophilic antibiotics is recommended and percutaneous cyst drainage may be required.Intracranial Aneurysms
Affected individuals with a family history of intracranial aneurysms or who have had a previously ruptured aneurysm should be periodically screened for the development of aneurysms. If an aneurysm is large enough, physicians may recommend surgical clipping of the aneurysm, in which a metal clip (usually titanium) is placed at the base or neck of the aneurysms where it bulges out from the blood vessel. This clip prevents blood from flowing into the aneurysm.End Stage Renal Disease (ERSD)
Individuals with end stage renal disease, in which the kidneys no longer function, require dialysis. Hemodialysis is a procedure in which a machine is used to rinse the blood and remove waste products from the bloodstream, helping to control blood pressure and helping to maintain proper levels of essential chemicals such as potassium. With peritoneal dialysis, the rinsing fluid is placed in the abdominal cavity for several hours and then withdrawn Individuals with ADPKD generally tend to do better on dialysis than individuals undergoing dialysis for other reasons.End stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant. | Therapies of Autosomal Dominant Polycystic Kidney Disease. Treatment
The treatment of individuals with ADPKD involves detailed attention to diet, fluid intake, blood pressure control and the avoidance of harmful drug and life-style choices. Implementation of these measures early in the course of the disease should slow the progression of kidney (renal) disease and preserve kidney function to some extent. . Effective treatment requires the coordinated efforts of a team of specialists working together to systematically and comprehensively plan an affected individual's personal prescription. Such specialists may include primary care family physicians, pediatricians or internists who collaborate with physicians specializing in disorders of the kidneys (nephrologists), surgical disorders of the urinary tract (urologists), dietitians, and/or other health care professionals. Genetic counseling may be of benefit for affected individuals and their families.Hypertension
In individuals with ADPKD, therapy typically includes aggressive treatment of high blood pressure (hypertension). Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) are preferred by most specialists who treat hypertension in ADPKD patients. These drugs block substances known to cause the hypertension by narrowing blood vessels (constrict) within the cystic kidneys. In individuals with ADPKD, these drugs may be more effective in preserving kidney function and preventing left ventricular hypertrophy than other therapies for hypertension.Pain
Pain associated with ADPKD can be treated in several ways. Acute pain associated with the rupture of a cyst into adjacent kidney tissue or into the urine collecting system can usually be treated with additional fluid intake, bed rest, and analgesics. Acute pain caused by infections, kidney stones, or a tumor will require an intervention study to be ruled out. Individuals with chronic, mild pain may be able to control it with over-the-counter medications containing acetaminophen. Long-term use of drugs that are toxic to the kidneys such as combination analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided. For more disabling pain, tricyclic antidepressant drugs or narcotics may be necessary. Splanchic nerve blockade, a procedure in which the injection of local anesthesia or steroids into certain nerves provides temporary relief of pain and ablation of nerves to the kidneys may give some relief. In rare cases a catastrophic decline in the quality of life may necessitate percutaneous cyst decompression, surgical incision and drainage of cysts, or even nephrectomy.Lifestyle Modification
Research has indicated that certain lifestyle modifications may be beneficial for some individuals with ADPKD. Although no specific diet is proven to ameliorate disease progression, some physicians recommend that individuals with ADPKD avoid foods and drinks containing caffeine, limit the amount of protein they eat, and reduce the amount of salt in their diets. Diets should be enriched in fruits and vegetables to provide sufficient potassium and reduce the intake of acid-forming foods. Affected individuals are also encouraged to exercise as much as they are able, to not smoke and to drink extra water throughout the day. Adults are advised to drink 3 liters (quarts) per day and children proportionately less.Cyst Complications
In some cases, as cysts grow larger they cause obstruction or compression of nearby structures such as organs or blood vessels. In these cases, surgery may be necessary to drain cysts. Cysts can also rupture causing bleeding (hemorrhaging) or become infected. Cyst hemorrhaging usually responds to bed rest, certain painkillers (analgesics), and fluid intake (hydration) to prevent the formation of obstructing blood clots.Cyst infections may be difficult to treat and require aggressive antibiotic therapy. However, because antibiotics have difficulty penetrating cysts, this therapy is not always effective. Lipophilic antibiotics (floxacin derivatives) are most effective in troublesome infections. When infected cysts do not respond to antibiotic therapy, surgery to drain the cysts may be necessary.Kidney Stones (Nephrolithiasis)
Individuals with ADPKD should drink plenty of water as a preventive (prophylactic) measure against the formation of kidney stones. Individuals with chronic stone formation should take in 3-4 liters of water and potassium citrate. In some cases, extracorporeal shock-wave lithotripsy (in which shock waves are used to break apart kidney stones) or percutaneous nephrostolithotomy (in which a needle is passed through the skin into the kidney to remove small stones) may be used to treat affected individuals.Urinary Tract Infections
Chronic urinary tract infections or kidney infections should be promptly treated with antibiotics to prevent the spread of infection to cysts within the kidneys, which is much more difficult to treat. Women with ADPKD are more susceptible to developing urinary tract infections than men.Polycystic Liver Disease
In most cases, polycystic liver disease does not require treatment. When polycystic liver disease causes symptoms, affected individuals may be advised to avoid caffeine and estrogens (e.g., hormone replacement therapy). In women who require hormone replacement therapy, transdermal preparations avoid sending high concentrations of drug to the liver as occurs when they are taken by mouth. Certain medications such as proton pump inhibitors, which reduce acids level in the stomach, or H2 blockers may be used to provide relief from gastro-esophageal reflux disease (GERD).In severe cases, certain procedures may be required to reduce the number of cysts and the size of the liver. Such procedures include percutaneous cyst aspiration, in which a needle is passed through the skin to drain fluid from a cyst; laparoscopic cyst fenestration, in which a small incision is made in the abdominal wall allowing a surgeon to cut a hole into the cyst through which the fluid to drains into the abdominal cavity; and surgical removal (resection) of part of the liver along with cyst fenestration. In rare cases, a liver transplant may be required. The specific procedure used depends on several factors including the progression of the disease, the size, number and location of the cysts, an individual’s age and general health, and other elements.In some cases, liver cysts may become infected. Treatment with lipophilic antibiotics is recommended and percutaneous cyst drainage may be required.Intracranial Aneurysms
Affected individuals with a family history of intracranial aneurysms or who have had a previously ruptured aneurysm should be periodically screened for the development of aneurysms. If an aneurysm is large enough, physicians may recommend surgical clipping of the aneurysm, in which a metal clip (usually titanium) is placed at the base or neck of the aneurysms where it bulges out from the blood vessel. This clip prevents blood from flowing into the aneurysm.End Stage Renal Disease (ERSD)
Individuals with end stage renal disease, in which the kidneys no longer function, require dialysis. Hemodialysis is a procedure in which a machine is used to rinse the blood and remove waste products from the bloodstream, helping to control blood pressure and helping to maintain proper levels of essential chemicals such as potassium. With peritoneal dialysis, the rinsing fluid is placed in the abdominal cavity for several hours and then withdrawn Individuals with ADPKD generally tend to do better on dialysis than individuals undergoing dialysis for other reasons.End stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant. | 130 | Autosomal Dominant Polycystic Kidney Disease |
nord_131_0 | Overview of Autosomal Dominant Porencephaly Type I | Autosomal dominant porencephaly type I is a rare genetic disorder in which fluid-filled cysts and cavities develop on the surface of the brain. Autosomal dominant porencephaly type I is caused by changes (mutations or pathogenic variants) in the COL4A1 gene. Affected individuals are predisposed to damage to small blood vessels, including the small vessels within the brain. The signs and symptoms of this disorder vary greatly from one individual to another but may include weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, varying degrees of cognitive impairment and migraines.Variants in the COL4A1 gene also cause at least two other disorders – brain small vessel disease with hemorrhage and HANAC (hereditary angiopathy with neuropathy, aneurysms, and muscle cramps) syndrome. Researchers now know that these three disorders represent a spectrum or continuum of disease with overlapping features. | Overview of Autosomal Dominant Porencephaly Type I. Autosomal dominant porencephaly type I is a rare genetic disorder in which fluid-filled cysts and cavities develop on the surface of the brain. Autosomal dominant porencephaly type I is caused by changes (mutations or pathogenic variants) in the COL4A1 gene. Affected individuals are predisposed to damage to small blood vessels, including the small vessels within the brain. The signs and symptoms of this disorder vary greatly from one individual to another but may include weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, varying degrees of cognitive impairment and migraines.Variants in the COL4A1 gene also cause at least two other disorders – brain small vessel disease with hemorrhage and HANAC (hereditary angiopathy with neuropathy, aneurysms, and muscle cramps) syndrome. Researchers now know that these three disorders represent a spectrum or continuum of disease with overlapping features. | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_1 | Symptoms of Autosomal Dominant Porencephaly Type I | The age of onset, specific symptoms, disease progression and severity of autosomal dominant porencephaly type I vary greatly from one individual to another, even among members of the same family. The term porencephaly refers to the formation of fluid-filled cysts or cavities on the surface of the brain. The size and exact locations of such cysts and cavities contribute to the clinical variability of this disorder. In some children, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Still other individuals may not develop any symptoms (asymptomatic) until well into adulthood. Affected individuals should talk to their physicians and medical team about their specific medical history and associated symptoms.Symptoms that may occur in individuals with autosomal dominant type I porencephaly include migraines, weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, stroke, varying degrees of intellectual disability and dystonia, a group of neurological disorders characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions.Additional features that may be associated with autosomal dominant porencephaly type I include poor or absent speech development, facial paralysis (paresis), involuntary muscle spasms (spasticity) that result in slow, stiff, rigid movements, visual field defects and hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms.Some individuals with autosomal dominant porencephaly type I may have additional symptoms sometimes associated with variants in the COL4A1 gene. For more information, see the COL4A1-related disorders in the Related Disorders section below. | Symptoms of Autosomal Dominant Porencephaly Type I. The age of onset, specific symptoms, disease progression and severity of autosomal dominant porencephaly type I vary greatly from one individual to another, even among members of the same family. The term porencephaly refers to the formation of fluid-filled cysts or cavities on the surface of the brain. The size and exact locations of such cysts and cavities contribute to the clinical variability of this disorder. In some children, serious, life-threatening complications may occur in infancy; in others, only minor complications may occur and intelligence is unaffected. Still other individuals may not develop any symptoms (asymptomatic) until well into adulthood. Affected individuals should talk to their physicians and medical team about their specific medical history and associated symptoms.Symptoms that may occur in individuals with autosomal dominant type I porencephaly include migraines, weakness or paralysis of one side of the body (hemiparesis or hemiplegia), seizures, stroke, varying degrees of intellectual disability and dystonia, a group of neurological disorders characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions.Additional features that may be associated with autosomal dominant porencephaly type I include poor or absent speech development, facial paralysis (paresis), involuntary muscle spasms (spasticity) that result in slow, stiff, rigid movements, visual field defects and hydrocephalus, a condition in which accumulation of excessive cerebrospinal fluid in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms.Some individuals with autosomal dominant porencephaly type I may have additional symptoms sometimes associated with variants in the COL4A1 gene. For more information, see the COL4A1-related disorders in the Related Disorders section below. | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_2 | Causes of Autosomal Dominant Porencephaly Type I | This genetic form of porencephaly is caused by variants in the COL4A1 gene and is inherited in an autosomal dominant pattern. Most individuals with autosomal dominant porencephaly type I have a parent with a pathogenic variant in the COL4A1 gene. In an unknown number of cases, the COL4A1 variant occurs randomly for no apparent reason (de novo).Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. The altered gene can be inherited from either parent or can be the result of a new variant (gene change) in the affected individual. The risk of passing the altered gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.The COL4A1 gene contains instructions for creating a protein known as collage type IV. Collagen type IV is essential for the proper strength and function of the vascular basement membrane, which is the thin membrane that lines blood vessels. Pathogenic variants in the COL4A1 gene result in deficient levels or defective function of collagen type IV, which, in turn, results in structural weakening of the vascular basement membrane predisposing blood vessels to damage or rupture. Because the blood vessels are structurally weakened, environmental factors such as trauma (including birth trauma in infants with a COL4A1 variant) are much more likely to cause rupture or damage to the vessels. Damaged blood vessels within the skull result in bleeding on the brain or lack of blood flow (ischemia) to the brain and, subsequently, damage to brain tissue. The cavities or cysts that characterize porencephaly form at the sites of brain tissue damage. | Causes of Autosomal Dominant Porencephaly Type I. This genetic form of porencephaly is caused by variants in the COL4A1 gene and is inherited in an autosomal dominant pattern. Most individuals with autosomal dominant porencephaly type I have a parent with a pathogenic variant in the COL4A1 gene. In an unknown number of cases, the COL4A1 variant occurs randomly for no apparent reason (de novo).Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an altered gene is necessary for the appearance of the disease. The altered gene can be inherited from either parent or can be the result of a new variant (gene change) in the affected individual. The risk of passing the altered gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females.The COL4A1 gene contains instructions for creating a protein known as collage type IV. Collagen type IV is essential for the proper strength and function of the vascular basement membrane, which is the thin membrane that lines blood vessels. Pathogenic variants in the COL4A1 gene result in deficient levels or defective function of collagen type IV, which, in turn, results in structural weakening of the vascular basement membrane predisposing blood vessels to damage or rupture. Because the blood vessels are structurally weakened, environmental factors such as trauma (including birth trauma in infants with a COL4A1 variant) are much more likely to cause rupture or damage to the vessels. Damaged blood vessels within the skull result in bleeding on the brain or lack of blood flow (ischemia) to the brain and, subsequently, damage to brain tissue. The cavities or cysts that characterize porencephaly form at the sites of brain tissue damage. | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_3 | Affects of Autosomal Dominant Porencephaly Type I | Autosomal dominant porencephaly type I affects males and females in equal numbers. The incidence of the disorder in the general population is unknown. Autosomal dominant porencephaly type I may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of this disorder. | Affects of Autosomal Dominant Porencephaly Type I. Autosomal dominant porencephaly type I affects males and females in equal numbers. The incidence of the disorder in the general population is unknown. Autosomal dominant porencephaly type I may go undiagnosed or misdiagnosed, making it difficult to determine the true frequency of this disorder. | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_4 | Related disorders of Autosomal Dominant Porencephaly Type I | Symptoms of the following disorders can be similar to those of autosomal dominant porencephaly type I. Comparisons may be useful for a differential diagnosis.COL4A1-related disorders are a group of rare disorders characterized by damage to small blood vessels, including those in the brain. The age of onset, disease progression, specific symptoms and disease severity varies greatly from one person to another. In addition to autosomal dominant porencephaly type I, two other disorders that are caused by COL4A1 variants include brain small vessel disease with hemorrhage and HANAC (hereditary angiopathy with neuropathy, aneurysms, and muscle cramps) syndrome. Symptoms may include paralysis on one side of the body (hemiparesis or hemiplegia), migraines, stroke and cognitive impairment. HANAC syndrome is associated with systemic disease and can involve the kidneys, muscles and small blood vessels of the eyes. In some individuals, including adults who previously had no symptoms, the first symptom of a COL4A1 variant is intracerebral hemorrhaging or bleeding in the brain caused by rupturing of blood vessels within the head. Affected individuals may also experience stroke-like symptoms. COL4A1-related disorders are inherited in an autosomal dominant pattern.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare genetic disorder characterized by damage to small- and medium-sized blood vessels, especially those in the brain. CADASIL potentially causes a wide variety of symptoms including migraines, strokes, cognitive impairment, speech problems, vision abnormalities and changes in personality and behavior. CADASIL eventually progresses to cause dementia. Affected individuals may be at a higher risk than the general population of developing a heart attack. The symptoms, age of onset, and disease progression vary greatly from individual to another. CADASIL is caused by pathogenic variants in the NOTCH3 gene. (For more information on this disorder, choose “CADASIL” as your search term in the Rare Disease Database.)Sporadic porencephaly is a rare disorder affecting the central nervous system. In porencephaly, cysts or cavities form on the surface of the brain. These cysts or cavities may become filled with cerebrospinal fluid, a colorless fluid that normally surrounds the brain and spinal cord to provide protection and nourishment. The severity and associated symptoms of porencephaly vary dramatically from one person to another based upon the size and exact locations of the fluid-filled cavities or cysts. Some infants develop serious complications shortly after birth; other individuals may have mild symptoms that may go undetected. (For more information on this disorder, choose “sporadic porencephaly” as your search term in the Rare Disease Database.) | Related disorders of Autosomal Dominant Porencephaly Type I. Symptoms of the following disorders can be similar to those of autosomal dominant porencephaly type I. Comparisons may be useful for a differential diagnosis.COL4A1-related disorders are a group of rare disorders characterized by damage to small blood vessels, including those in the brain. The age of onset, disease progression, specific symptoms and disease severity varies greatly from one person to another. In addition to autosomal dominant porencephaly type I, two other disorders that are caused by COL4A1 variants include brain small vessel disease with hemorrhage and HANAC (hereditary angiopathy with neuropathy, aneurysms, and muscle cramps) syndrome. Symptoms may include paralysis on one side of the body (hemiparesis or hemiplegia), migraines, stroke and cognitive impairment. HANAC syndrome is associated with systemic disease and can involve the kidneys, muscles and small blood vessels of the eyes. In some individuals, including adults who previously had no symptoms, the first symptom of a COL4A1 variant is intracerebral hemorrhaging or bleeding in the brain caused by rupturing of blood vessels within the head. Affected individuals may also experience stroke-like symptoms. COL4A1-related disorders are inherited in an autosomal dominant pattern.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare genetic disorder characterized by damage to small- and medium-sized blood vessels, especially those in the brain. CADASIL potentially causes a wide variety of symptoms including migraines, strokes, cognitive impairment, speech problems, vision abnormalities and changes in personality and behavior. CADASIL eventually progresses to cause dementia. Affected individuals may be at a higher risk than the general population of developing a heart attack. The symptoms, age of onset, and disease progression vary greatly from individual to another. CADASIL is caused by pathogenic variants in the NOTCH3 gene. (For more information on this disorder, choose “CADASIL” as your search term in the Rare Disease Database.)Sporadic porencephaly is a rare disorder affecting the central nervous system. In porencephaly, cysts or cavities form on the surface of the brain. These cysts or cavities may become filled with cerebrospinal fluid, a colorless fluid that normally surrounds the brain and spinal cord to provide protection and nourishment. The severity and associated symptoms of porencephaly vary dramatically from one person to another based upon the size and exact locations of the fluid-filled cavities or cysts. Some infants develop serious complications shortly after birth; other individuals may have mild symptoms that may go undetected. (For more information on this disorder, choose “sporadic porencephaly” as your search term in the Rare Disease Database.) | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_5 | Diagnosis of Autosomal Dominant Porencephaly Type I | A diagnosis of autosomal dominant porencephaly type I is suspected based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as advanced imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. A MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.A diagnosis can be confirmed by molecular genetic testing, in which a person’s DNA is tested for variants in the COL4A1 gene that cause autosomal dominant porencephaly type I. Molecular genetic testing for this disorder is available on a clinical basis. | Diagnosis of Autosomal Dominant Porencephaly Type I. A diagnosis of autosomal dominant porencephaly type I is suspected based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as advanced imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. A MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.A diagnosis can be confirmed by molecular genetic testing, in which a person’s DNA is tested for variants in the COL4A1 gene that cause autosomal dominant porencephaly type I. Molecular genetic testing for this disorder is available on a clinical basis. | 131 | Autosomal Dominant Porencephaly Type I |
nord_131_6 | Therapies of Autosomal Dominant Porencephaly Type I | The treatment of autosomal dominant porencephaly type I is geared toward the specific symptoms that are present in each individual. For example, treatment may include physical therapy, speech therapy, anti-convulsant medications for seizures and a shunt to treat hydrocephalus by draining excess fluid from the skull. Individuals with high blood pressure (hypertension) must receive appropriate therapy because of the increased risk of stroke. Smoking, which also increases the risk of stroke, physical activities that can cause head trauma and the use of anti-clotting (anticoagulant) medications should also be avoided.Early intervention is important in ensuring that children with autosomal dominant porencephaly type I reach their highest potential. Services that may be beneficial for some affected individuals include medical, social and/or vocational services such as special remedial education.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Autosomal Dominant Porencephaly Type I. The treatment of autosomal dominant porencephaly type I is geared toward the specific symptoms that are present in each individual. For example, treatment may include physical therapy, speech therapy, anti-convulsant medications for seizures and a shunt to treat hydrocephalus by draining excess fluid from the skull. Individuals with high blood pressure (hypertension) must receive appropriate therapy because of the increased risk of stroke. Smoking, which also increases the risk of stroke, physical activities that can cause head trauma and the use of anti-clotting (anticoagulant) medications should also be avoided.Early intervention is important in ensuring that children with autosomal dominant porencephaly type I reach their highest potential. Services that may be beneficial for some affected individuals include medical, social and/or vocational services such as special remedial education.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | 131 | Autosomal Dominant Porencephaly Type I |
nord_132_0 | Overview of Autosomal Dominant Tubulo-Interstitial Kidney Disease | Autosomal dominant tubulointerstitial kidney disease (ADTKD) describes a group of diseases that affect the tubules of the kidney. These conditions have the following characteristics: They are inherited in an autosomal dominant manner; this means that a parent has a 50% chance of passing the disease on to their children. Often many family members are affected. (2) Chronic kidney disease develops. This initially is noticed as an elevated blood creatinine level. There are no symptoms from an elevated creatinine until it is very high, so often the elevated creatinine is found out on blood testing at a doctor’s office or in the hospital. Often, doctors are uncertain why the creatinine is elevated. As chronic kidney disease progresses, and the creatinine rises more, patients develop symptoms of fatigue, anemia, and feel cold all the time. Decreased appetite and fluid retention develop as the patient nears the need for dialysis. (3) Dialysis or kidney transplant is required sometime between the 4th and 7th decade of life. (4) Several types of the disease are associated with elevated uric acid concentrations in blood and gout, which sometimes starts in the teenage years. In ADTKD-UMOD and ADTKD- REN, some – but not all – family members are affected by gout.ADTKD-UMOD (also known as uromodulin kidney disease) is the most common form of this condition. It is caused by a mutation in a gene producing a protein called uromodulin. This protein is only made in the kidney. The mutation causes affected individuals to develop gout, frequently in their teenage years, and progressive kidney disease. This particular condition has previously been called familial juvenile hyperuricemic nephropathy type1 or medullary cystic kidney disease type 2. Preferred terms at present include ADTKD-UMOD and uromodulin kidney disease (UKD).ADTKD-REN is caused by mutations in the gene producing a protein called renin. There are several types of this disorder. Children can present as early as infancy with elevated blood potassium levels, low blood bicarbonate levels, decreased kidney function, and anemia. Some individuals present later in childhood with anemia and decreased kidney function. Often, their blood potassium levels are mildly elevated, and their blood uric acid levels are also elevated. These individuals also suffer from gout. Some families with this disorder may have a less severe mutation and may present in their early twenties with gout and later develop chronic kidney disease. This condition has previously been called familial juvenile hyperuricemic nephropathy type 2.ADTKD-MUC1 (MUC1 kidney disease) is due to mutations in the gene producing the protein mucin-1. Patients with this type of autosomal dominant tubulointerstitial kidney disease have slowly progressive chronic kidney disease. They do not have any symptoms when they are young, but as they get older, their kidney function declines. Mildly decreased kidney function may first be noted in the late teens/early twenties, and affected individuals usually require dialysis or a kidney transplant between the 3rd and seventh decades of life. Unlike the other types of the disease (uromodulin kidney disease or disease due to renin mutations), patients with MUC1 mutations do not have frequent gout, anemia or other symptoms.Autosomal dominant tubulotubulointerstitial kidney disease of unknown genetic cause is the term used to describe families with this disease in whom the cause is not known. These individuals usually have chronic kidney disease but do not have gout. Researchers are now trying to find the cause of this disease. Some of these families have mutations in the MUC1 gene that have not yet been identified and are difficult to find. | Overview of Autosomal Dominant Tubulo-Interstitial Kidney Disease. Autosomal dominant tubulointerstitial kidney disease (ADTKD) describes a group of diseases that affect the tubules of the kidney. These conditions have the following characteristics: They are inherited in an autosomal dominant manner; this means that a parent has a 50% chance of passing the disease on to their children. Often many family members are affected. (2) Chronic kidney disease develops. This initially is noticed as an elevated blood creatinine level. There are no symptoms from an elevated creatinine until it is very high, so often the elevated creatinine is found out on blood testing at a doctor’s office or in the hospital. Often, doctors are uncertain why the creatinine is elevated. As chronic kidney disease progresses, and the creatinine rises more, patients develop symptoms of fatigue, anemia, and feel cold all the time. Decreased appetite and fluid retention develop as the patient nears the need for dialysis. (3) Dialysis or kidney transplant is required sometime between the 4th and 7th decade of life. (4) Several types of the disease are associated with elevated uric acid concentrations in blood and gout, which sometimes starts in the teenage years. In ADTKD-UMOD and ADTKD- REN, some – but not all – family members are affected by gout.ADTKD-UMOD (also known as uromodulin kidney disease) is the most common form of this condition. It is caused by a mutation in a gene producing a protein called uromodulin. This protein is only made in the kidney. The mutation causes affected individuals to develop gout, frequently in their teenage years, and progressive kidney disease. This particular condition has previously been called familial juvenile hyperuricemic nephropathy type1 or medullary cystic kidney disease type 2. Preferred terms at present include ADTKD-UMOD and uromodulin kidney disease (UKD).ADTKD-REN is caused by mutations in the gene producing a protein called renin. There are several types of this disorder. Children can present as early as infancy with elevated blood potassium levels, low blood bicarbonate levels, decreased kidney function, and anemia. Some individuals present later in childhood with anemia and decreased kidney function. Often, their blood potassium levels are mildly elevated, and their blood uric acid levels are also elevated. These individuals also suffer from gout. Some families with this disorder may have a less severe mutation and may present in their early twenties with gout and later develop chronic kidney disease. This condition has previously been called familial juvenile hyperuricemic nephropathy type 2.ADTKD-MUC1 (MUC1 kidney disease) is due to mutations in the gene producing the protein mucin-1. Patients with this type of autosomal dominant tubulointerstitial kidney disease have slowly progressive chronic kidney disease. They do not have any symptoms when they are young, but as they get older, their kidney function declines. Mildly decreased kidney function may first be noted in the late teens/early twenties, and affected individuals usually require dialysis or a kidney transplant between the 3rd and seventh decades of life. Unlike the other types of the disease (uromodulin kidney disease or disease due to renin mutations), patients with MUC1 mutations do not have frequent gout, anemia or other symptoms.Autosomal dominant tubulotubulointerstitial kidney disease of unknown genetic cause is the term used to describe families with this disease in whom the cause is not known. These individuals usually have chronic kidney disease but do not have gout. Researchers are now trying to find the cause of this disease. Some of these families have mutations in the MUC1 gene that have not yet been identified and are difficult to find. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_1 | Symptoms of Autosomal Dominant Tubulo-Interstitial Kidney Disease | All individuals with ADTKD show slow loss of kidney function that may be present as early as childhood. Patients may first be diagnosed with this disease when they are found to have an elevated blood creatinine level (measure of kidney function) on a routine blood test at their doctor’s office. For many individuals, there may be no other symptoms. Doctors will check the urine, and will find that it does not contain blood and little or no protein. A kidney ultrasound is usually normal, and even a kidney biopsy may not point to a cause for this condition. Doctors are often confused because the patient has an elevated creatinine but the urine tests and the kidney ultrasound look normal. Thus, ADTKD is frequently not properly diagnosed. The kidney disease progresses slowly, and patients eventually develop symptoms of kidney failure (nausea, fluid retention) and require dialysis or kidney transplant. The age that kidney transplant or dialysis is required is highly variable, with some individuals requiring it as early as age 17, while other family members may not even require it at age 70. The reason for this variation is unclear.Individuals with ADTKD-MUC1 only have symptoms of chronic kidney disease progression and do not suffer from other distinctive symptoms, making this form of the disease even more difficult to diagnose.In addition to chronic kidney disease, patients with ADTKD-UMOD have elevated levels of blood uric acid that can lead to gout. Gout is a form of arthritis (joint inflammation) that commonly affects the big toe, knee, elbow, or other joints. Gout is usually a disease of middle-aged men. Therefore, gout may be misdiagnosed in teenagers with this condition. When gout is diagnosed, doctors frequently are unsure why the gout is present. While many families with ADTKD-UMOD have gout, it is not present in all families.In addition to high uric acid levels, gout, and chronic kidney disease, Individuals with ADTKD-REN all suffer from anemia early in life, being present as early as one year of age. Anemia usually resolves during adolescence but returns when kidney failure worsens (usually in the 30’s or 40’s). Often, the cause of the anemia is not known when diagnosed. Patients also tend to have low blood pressures and high blood potassium levels. Some, but not all, affected individuals produce more than normal amounts of urine, which can result in bed-wetting in childhood.Individuals with autosomal dominant tubulointerstitial kidney disease of unknown genetic cause are similar to those with disease due to MUC1 mutations, in that the only symptom is slowly progressive kidney disease. | Symptoms of Autosomal Dominant Tubulo-Interstitial Kidney Disease. All individuals with ADTKD show slow loss of kidney function that may be present as early as childhood. Patients may first be diagnosed with this disease when they are found to have an elevated blood creatinine level (measure of kidney function) on a routine blood test at their doctor’s office. For many individuals, there may be no other symptoms. Doctors will check the urine, and will find that it does not contain blood and little or no protein. A kidney ultrasound is usually normal, and even a kidney biopsy may not point to a cause for this condition. Doctors are often confused because the patient has an elevated creatinine but the urine tests and the kidney ultrasound look normal. Thus, ADTKD is frequently not properly diagnosed. The kidney disease progresses slowly, and patients eventually develop symptoms of kidney failure (nausea, fluid retention) and require dialysis or kidney transplant. The age that kidney transplant or dialysis is required is highly variable, with some individuals requiring it as early as age 17, while other family members may not even require it at age 70. The reason for this variation is unclear.Individuals with ADTKD-MUC1 only have symptoms of chronic kidney disease progression and do not suffer from other distinctive symptoms, making this form of the disease even more difficult to diagnose.In addition to chronic kidney disease, patients with ADTKD-UMOD have elevated levels of blood uric acid that can lead to gout. Gout is a form of arthritis (joint inflammation) that commonly affects the big toe, knee, elbow, or other joints. Gout is usually a disease of middle-aged men. Therefore, gout may be misdiagnosed in teenagers with this condition. When gout is diagnosed, doctors frequently are unsure why the gout is present. While many families with ADTKD-UMOD have gout, it is not present in all families.In addition to high uric acid levels, gout, and chronic kidney disease, Individuals with ADTKD-REN all suffer from anemia early in life, being present as early as one year of age. Anemia usually resolves during adolescence but returns when kidney failure worsens (usually in the 30’s or 40’s). Often, the cause of the anemia is not known when diagnosed. Patients also tend to have low blood pressures and high blood potassium levels. Some, but not all, affected individuals produce more than normal amounts of urine, which can result in bed-wetting in childhood.Individuals with autosomal dominant tubulointerstitial kidney disease of unknown genetic cause are similar to those with disease due to MUC1 mutations, in that the only symptom is slowly progressive kidney disease. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_2 | Causes of Autosomal Dominant Tubulo-Interstitial Kidney Disease | All types of autosomal dominant tubulointerstitial kidney disease follow autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. We all have two copies of each gene. Individuals with ADTKD have one normal copy and one abnormal copy. The parent has a 50/50 chance of passing the abnormal gene on to their child. Thus, children of an affected individual have a 50/50 chance of having the disease. The risk is the same for males and females. There are usually a number of family members affected, with at least a parent and child almost always affected.ADTKD-UMOD is caused by a mistake (mutation) in a gene that encodes the protein called uromodulin. The abnormal protein builds up in kidney cells and causes slow progression of kidney disease. The reason why affected individuals develop gout is unclear, but likely related to improper function of kidney cells and/or abnormally low amounts of the uromodulin in sites where it is needed.ADTKD-REN is caused by a mutation in a gene that encodes the protein called renin. The abnormal protein either builds up in kidney cells or is not produced in substantial amounts when needed, and this causes slow progression of kidney disease. Because affected individuals have low amounts of normal renin, patients may have mildly low blood pressure and mildly high potassium levels.ADTKD-MUC1 is caused by a mutation in the gene that encodes mucoprotein-1. Mucoprotein-1 is a protein that is made in many of the cells of the body and provides a protective lining to the stomach, lungs, kidney tubules, and many other areas of the body. For some reason, the mutation only leads to problems in the kidney, and every other organ/tissue is completely normal.Autosomal dominant tubulointerstitial kidney disease of unknown cause is caused by a mutation in a gene, but the gene that causes the disease is not yet known. | Causes of Autosomal Dominant Tubulo-Interstitial Kidney Disease. All types of autosomal dominant tubulointerstitial kidney disease follow autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. We all have two copies of each gene. Individuals with ADTKD have one normal copy and one abnormal copy. The parent has a 50/50 chance of passing the abnormal gene on to their child. Thus, children of an affected individual have a 50/50 chance of having the disease. The risk is the same for males and females. There are usually a number of family members affected, with at least a parent and child almost always affected.ADTKD-UMOD is caused by a mistake (mutation) in a gene that encodes the protein called uromodulin. The abnormal protein builds up in kidney cells and causes slow progression of kidney disease. The reason why affected individuals develop gout is unclear, but likely related to improper function of kidney cells and/or abnormally low amounts of the uromodulin in sites where it is needed.ADTKD-REN is caused by a mutation in a gene that encodes the protein called renin. The abnormal protein either builds up in kidney cells or is not produced in substantial amounts when needed, and this causes slow progression of kidney disease. Because affected individuals have low amounts of normal renin, patients may have mildly low blood pressure and mildly high potassium levels.ADTKD-MUC1 is caused by a mutation in the gene that encodes mucoprotein-1. Mucoprotein-1 is a protein that is made in many of the cells of the body and provides a protective lining to the stomach, lungs, kidney tubules, and many other areas of the body. For some reason, the mutation only leads to problems in the kidney, and every other organ/tissue is completely normal.Autosomal dominant tubulointerstitial kidney disease of unknown cause is caused by a mutation in a gene, but the gene that causes the disease is not yet known. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_3 | Affects of Autosomal Dominant Tubulo-Interstitial Kidney Disease | All types of autosomal dominant tubulointerstitial kidney disease are very uncommon. | Affects of Autosomal Dominant Tubulo-Interstitial Kidney Disease. All types of autosomal dominant tubulointerstitial kidney disease are very uncommon. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_4 | Related disorders of Autosomal Dominant Tubulo-Interstitial Kidney Disease | Symptoms of the following disorders can be similar to those of autosomal dominant tubulointerstitial kidney disease. Comparisons may be useful for a differential diagnosis.Polycystic kidney disease is an inherited disorder characterized by the presence of cysts in both kidneys. Progressive enlargement of these cysts causes the loss of normal kidney function and high blood pressure. There are childhood and adult forms of polycystic kidney disease. Symptoms may include abdominal enlargement, back pain, blood in the urine (hematuria), high blood pressure (hypertension), weight loss, and/or unusually low levels of fluid in the body (dehydration). Some people with this disorder may also have liver problems and abnormal enlargement of the spleen (splenomegaly). Cysts are always seen in the kidneys of families with this condition, making it easy to differentiate from other types of kidney disease. (For more information on this disorder, choose “Polycystic Kidney” as your search term in the Rare Disease Database.)Nephronophthisis is a similar condition. It is characterized by slowly progressive kidney failure. The examination of the urine in this condition also reveals no blood and little protein. A key difference between this condition and ADTKD is that it is autosomal recessive. In this condition, a single child or siblings may be affected. Unlike ADTKD, a parent and a child are NOT both affected. In addition, kidney failure occurs in childhood, with most individuals requiring dialysis by age 15-25 years; and other symptoms often occur in nephronophthisis (though not always). These symptoms include anemia, producing excessive amounts of urine, and blindness in some individuals. | Related disorders of Autosomal Dominant Tubulo-Interstitial Kidney Disease. Symptoms of the following disorders can be similar to those of autosomal dominant tubulointerstitial kidney disease. Comparisons may be useful for a differential diagnosis.Polycystic kidney disease is an inherited disorder characterized by the presence of cysts in both kidneys. Progressive enlargement of these cysts causes the loss of normal kidney function and high blood pressure. There are childhood and adult forms of polycystic kidney disease. Symptoms may include abdominal enlargement, back pain, blood in the urine (hematuria), high blood pressure (hypertension), weight loss, and/or unusually low levels of fluid in the body (dehydration). Some people with this disorder may also have liver problems and abnormal enlargement of the spleen (splenomegaly). Cysts are always seen in the kidneys of families with this condition, making it easy to differentiate from other types of kidney disease. (For more information on this disorder, choose “Polycystic Kidney” as your search term in the Rare Disease Database.)Nephronophthisis is a similar condition. It is characterized by slowly progressive kidney failure. The examination of the urine in this condition also reveals no blood and little protein. A key difference between this condition and ADTKD is that it is autosomal recessive. In this condition, a single child or siblings may be affected. Unlike ADTKD, a parent and a child are NOT both affected. In addition, kidney failure occurs in childhood, with most individuals requiring dialysis by age 15-25 years; and other symptoms often occur in nephronophthisis (though not always). These symptoms include anemia, producing excessive amounts of urine, and blindness in some individuals. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_5 | Diagnosis of Autosomal Dominant Tubulo-Interstitial Kidney Disease | Several lab tests are very helpful in pointing to this diagnosis. First, a blood test is done to measure the blood creatinine. In this condition, the blood creatinine is usually elevated, beginning in the second decade of life. A blood uric acid level is also tested and is almost always elevated in ADTKD-UMOD and ADTKD-REN (though not elevated early on in ADTKD-MUC1). A urine test (urinalysis) is done. The absence of blood or protein in the urine rules out other possible causes of kidney damage. Thus, most individuals with this condition have high blood creatinine levels, and a normal urinalysis. A kidney ultrasound is also frequently done and usually shows normal kidneys, though some individuals may be found to have cysts in the middle of the kidney. The real key to the diagnosis is that a parent and a child are usually both affected with kidney disease. Kidney biopsy may be performed, but the kidney biopsy cannot specifically diagnose ADTKD: genetic testing is required.Molecular genetic testing is available for ADKTD-MUC1, ADTKD-UMOD, and ADTKD-REN. Genetic testing for ADTKD-UMOD and ADTKD-REN is available in commercial laboratories. ADTKD-MUC1 testing is available at present free of charge from the Broad Institute, Boston, Massachusetts. In order to arrange for this testing, please contact Anthony Bleyer MD at [email protected].If no mutations are found, individuals have autosomal dominant tubulointerstitial kidney disease of unknown genetic cause. Further genetic testing can be done at academic medical centers to help diagnose this disease. Contact [email protected] for further information. | Diagnosis of Autosomal Dominant Tubulo-Interstitial Kidney Disease. Several lab tests are very helpful in pointing to this diagnosis. First, a blood test is done to measure the blood creatinine. In this condition, the blood creatinine is usually elevated, beginning in the second decade of life. A blood uric acid level is also tested and is almost always elevated in ADTKD-UMOD and ADTKD-REN (though not elevated early on in ADTKD-MUC1). A urine test (urinalysis) is done. The absence of blood or protein in the urine rules out other possible causes of kidney damage. Thus, most individuals with this condition have high blood creatinine levels, and a normal urinalysis. A kidney ultrasound is also frequently done and usually shows normal kidneys, though some individuals may be found to have cysts in the middle of the kidney. The real key to the diagnosis is that a parent and a child are usually both affected with kidney disease. Kidney biopsy may be performed, but the kidney biopsy cannot specifically diagnose ADTKD: genetic testing is required.Molecular genetic testing is available for ADKTD-MUC1, ADTKD-UMOD, and ADTKD-REN. Genetic testing for ADTKD-UMOD and ADTKD-REN is available in commercial laboratories. ADTKD-MUC1 testing is available at present free of charge from the Broad Institute, Boston, Massachusetts. In order to arrange for this testing, please contact Anthony Bleyer MD at [email protected].If no mutations are found, individuals have autosomal dominant tubulointerstitial kidney disease of unknown genetic cause. Further genetic testing can be done at academic medical centers to help diagnose this disease. Contact [email protected] for further information. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_132_6 | Therapies of Autosomal Dominant Tubulo-Interstitial Kidney Disease | TreatmentMany affected individuals with ADTKD-UMOD and ADTKD-REN suffer from gout beginning in the teenage years. The gout is easily treated with a medication called allopurinol. Allopurinol is a medicine that is commonly used in the treatment of gout. It has been used for many years and by thousands of patients with gout. Patients occasionally have allergies to the medication, which rarely are severe. This medication easily controls gout in affected individuals. In uromodulin kidney disease, gout, if untreated, will continue and worsen over time. Therefore, early treatment is advisable. Febuxostat is an alternative to allopurinol. Both febuxostsat and allopurinol should be stopped immediately in pregnancy is considered or becoming pregnant is possible. There are other uric acid lowering therapies that can be considered and discussed with the treating physician.Some doctors believe that allopurinol can slow progression of kidney disease in ADTKD-UMOD, even in patients who do not have gout. It is not clear if allopurinol slows progression of disease. It does not appear to stop progression of the kidney disease entirely.For ADTKD-MUC, there are a group of medications called angiotensin converting enzyme (ACE) inhibitors that have been shown to slow progression of kidney failure in many kidney diseases. It is unclear if they slow progression of disease in uromodulin kidney disease, but it is possible.For patients with ADTKD-REN who have mildly high blood potassium and mildly low blood pressures, the medication fludrocortisone may be an effective treatment. This treatment was found to improve kidney function in one child with this disease, but did not have an effect on an older patient with advanced kidney disease. It is very important that patients with ADTKD-REN are NOT put on a low sodium diet, as this could worsen kidney function.Anemia occurring in childhood with ADTKD-REN may be treated with a medication called erythropoietin. This medication is given as a shot once every week or every other week and will correct the anemia. However, the anemia is usually mild and asymptomatic and may not require therapy.There are no specific treatments for ADTKD-MUC1 or ADTKD of unknown genetic cause.Individuals with renin mutations should avoid non-steroidal anti-inflammatory agents such as ibuprofen (Advil, Aleve) or naprosyn. | Therapies of Autosomal Dominant Tubulo-Interstitial Kidney Disease. TreatmentMany affected individuals with ADTKD-UMOD and ADTKD-REN suffer from gout beginning in the teenage years. The gout is easily treated with a medication called allopurinol. Allopurinol is a medicine that is commonly used in the treatment of gout. It has been used for many years and by thousands of patients with gout. Patients occasionally have allergies to the medication, which rarely are severe. This medication easily controls gout in affected individuals. In uromodulin kidney disease, gout, if untreated, will continue and worsen over time. Therefore, early treatment is advisable. Febuxostat is an alternative to allopurinol. Both febuxostsat and allopurinol should be stopped immediately in pregnancy is considered or becoming pregnant is possible. There are other uric acid lowering therapies that can be considered and discussed with the treating physician.Some doctors believe that allopurinol can slow progression of kidney disease in ADTKD-UMOD, even in patients who do not have gout. It is not clear if allopurinol slows progression of disease. It does not appear to stop progression of the kidney disease entirely.For ADTKD-MUC, there are a group of medications called angiotensin converting enzyme (ACE) inhibitors that have been shown to slow progression of kidney failure in many kidney diseases. It is unclear if they slow progression of disease in uromodulin kidney disease, but it is possible.For patients with ADTKD-REN who have mildly high blood potassium and mildly low blood pressures, the medication fludrocortisone may be an effective treatment. This treatment was found to improve kidney function in one child with this disease, but did not have an effect on an older patient with advanced kidney disease. It is very important that patients with ADTKD-REN are NOT put on a low sodium diet, as this could worsen kidney function.Anemia occurring in childhood with ADTKD-REN may be treated with a medication called erythropoietin. This medication is given as a shot once every week or every other week and will correct the anemia. However, the anemia is usually mild and asymptomatic and may not require therapy.There are no specific treatments for ADTKD-MUC1 or ADTKD of unknown genetic cause.Individuals with renin mutations should avoid non-steroidal anti-inflammatory agents such as ibuprofen (Advil, Aleve) or naprosyn. | 132 | Autosomal Dominant Tubulo-Interstitial Kidney Disease |
nord_133_0 | Overview of Autosomal Recessive Hyper IgE Syndrome | Autosomal recessive hyper IgE syndrome (AR-HIES) is a very rare primary immunodeficiency disorder. Symptoms often become apparent at birth or early during infancy or childhood. The disorder is characterized by the triad of highly elevated levels of IgE in serum, recurring abscesses of the skin, and recurrent pneumonia AR-HIES is inherited as an autosomal recessive trait and the first symptoms include the development of a dry, red, flaky skin rash (eczema).The clinical triad of AR-HIES is shared with the more frequent autosomal dominant HIES syndrome (AD-HIES; see this term), but other features such as persistent cutaneous viral infections and neurological symptoms are unique to the AR-HIES form. For years, researchers considered them different expressions of the same disorder, but now researchers consider them similar, yet distinct disorders.The first case of hyper IgE syndrome was described in the medical literature in 1966. The physicians termed the disorder Job syndrome after the biblical character of Job who was covered in boils and sores over his entire body. | Overview of Autosomal Recessive Hyper IgE Syndrome. Autosomal recessive hyper IgE syndrome (AR-HIES) is a very rare primary immunodeficiency disorder. Symptoms often become apparent at birth or early during infancy or childhood. The disorder is characterized by the triad of highly elevated levels of IgE in serum, recurring abscesses of the skin, and recurrent pneumonia AR-HIES is inherited as an autosomal recessive trait and the first symptoms include the development of a dry, red, flaky skin rash (eczema).The clinical triad of AR-HIES is shared with the more frequent autosomal dominant HIES syndrome (AD-HIES; see this term), but other features such as persistent cutaneous viral infections and neurological symptoms are unique to the AR-HIES form. For years, researchers considered them different expressions of the same disorder, but now researchers consider them similar, yet distinct disorders.The first case of hyper IgE syndrome was described in the medical literature in 1966. The physicians termed the disorder Job syndrome after the biblical character of Job who was covered in boils and sores over his entire body. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_1 | Symptoms of Autosomal Recessive Hyper IgE Syndrome | The symptoms of AR-HIES vary from case to case. AR-HIES affects the immune system as well as the central nervous system. Symptoms may be apparent at birth or during infancy or early childhood. AR-HIES is considered a rare primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against different infectious agents (i.e., invading microscopic life-forms [microorganisms]). The T cell system (cell-mediated immune response) is responsible for fighting yeast and fungi, several viruses, and some bacteria. The B cell system (humoral immune response) fights infection caused by other viruses and particularly encapsulated bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g., saliva). There are four major classes of immunoglobulins (Ig) known as IgM, IgG, IgA, and IgE. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. (The white blood cells [leukocytes] are part of the body's system of defenses, playing an essential role in protecting against infection as well as fighting infection once it occurs.) In addition, antibodies are produced following vaccination, providing protection from infectious diseases like polio, measles, and tetanus. Individuals with AR-HIES have abnormally high levels of immunoglobulin IgE in the fluid portion of the blood (thus the term “hyper IgE”). Affected individuals also have abnormal numbers of white blood cells known as eosinophils throughout the body (eosinophilia). Because of problems within the immune system, individuals with AR-HIES are susceptible to recurrent episodes of certain bacterial infections that affect the skin and lungs as well as recurrent viral infections. The first symptom of AR-HIES may be a dry, red flaky skin rash (eczema) that develops at birth or early during infancy. Itchiness (pruritus) may also occur. In addition, infants are particularly susceptible to bacterial infection, especially staphylococcal infections. Such infections may cause boils and pus-filled holes (abscesses) to form on the skin. These abscesses are referred to as “cold” abscesses because they lack the normal surrounding signs of infections such as warmth and redness. Abscesses may also be found on the bone behind the ear (mastoid), joints, gums, air passages in the lungs (bronchi), and in the lungs themselves. Individuals with AR-HIES also develop recurrent lung infections (pneumonia). Pneumonia is often associated with fluid accumulation around the lungs (pleural effusion) or pus in the area between the outer surface of the lung and the chest wall (empyema). Individuals with AR-HIES may develop repeated episodes of respiratory (bronchitis), sinus (sinusitis), and middle ear infections (otitis media). Skin infections associated with AR-HIES are most often caused by Staphylococcus aureus. Pneumonia and respiratory infections associated with AR-HIES are mainly due to a wide spectrum of gram-positive and gram-negative bacteria and fungi including Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis jirovecii and Histoplasma capsulaum. In addition to bacterial infections, individuals with AR-HIES are especially susceptible to viral infections such as herpes simplex (HSV) and herpes zoster (VZV), molluscum contagiosum (MCV) and human papillomavirus (HPV). These infections which are extensive, difficult to control and mutilating, often occur concurrently.Affected individuals have developed chronic orolabial or ulcerative anogenital infections with herpes simplex virus. Eczema herpeticum as well as inflammation of the cornea (keratitis) with herpes virus also occur. Some individuals with AR-HIES have developed a severe viral skin infection known as Molluscum contagiosum caused by the molluscum contagiosum virus (MCV). This infection is characterized by raised bumps or growths (nodules) on the skin that often become red or inflamed. Nodules may be tender and itchy as well. Repeated infections with the varicella zoster virus, the virus that causes chickenpox, have also been reported in literature.In addition to susceptibility to infection, individuals with AR-HIES can present a variety of neurological symptoms. Such symptoms include partial facial paralysis, tissue degeneration due to lack of blood flow (ischemic infarction), inflammation of blood vessels (vasculitis) of the brain, and paralysis on one side of the body (hemiplegia). Neurological symptoms may progress to cause life-threatening complications including bleeding (hemorrhaging) in the brain or widening or bulging of the wall of a brain artery or vein (aneurysm). Individuals with AR-HIES may also be prone to developing autoimmune disorders such as hemolytic anemia. The term autoimmune refers to conditions in which the body's natural defenses against invading microorganisms mistakenly attack healthy tissue. Hemolytic anemia is characterized by the premature destruction of red blood cells faster than they can be reproduced. Anemia may result in fatigue, paleness, rapid heartbeat, shortness of breath, dark urine, and chills.Unlike the more common AD-HIES, 50-70% of patients with AR-HIES develop severe allergies, including anaphylaxis to food and environmental antigens, and about 30% have asthma. | Symptoms of Autosomal Recessive Hyper IgE Syndrome. The symptoms of AR-HIES vary from case to case. AR-HIES affects the immune system as well as the central nervous system. Symptoms may be apparent at birth or during infancy or early childhood. AR-HIES is considered a rare primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against different infectious agents (i.e., invading microscopic life-forms [microorganisms]). The T cell system (cell-mediated immune response) is responsible for fighting yeast and fungi, several viruses, and some bacteria. The B cell system (humoral immune response) fights infection caused by other viruses and particularly encapsulated bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g., saliva). There are four major classes of immunoglobulins (Ig) known as IgM, IgG, IgA, and IgE. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells. (The white blood cells [leukocytes] are part of the body's system of defenses, playing an essential role in protecting against infection as well as fighting infection once it occurs.) In addition, antibodies are produced following vaccination, providing protection from infectious diseases like polio, measles, and tetanus. Individuals with AR-HIES have abnormally high levels of immunoglobulin IgE in the fluid portion of the blood (thus the term “hyper IgE”). Affected individuals also have abnormal numbers of white blood cells known as eosinophils throughout the body (eosinophilia). Because of problems within the immune system, individuals with AR-HIES are susceptible to recurrent episodes of certain bacterial infections that affect the skin and lungs as well as recurrent viral infections. The first symptom of AR-HIES may be a dry, red flaky skin rash (eczema) that develops at birth or early during infancy. Itchiness (pruritus) may also occur. In addition, infants are particularly susceptible to bacterial infection, especially staphylococcal infections. Such infections may cause boils and pus-filled holes (abscesses) to form on the skin. These abscesses are referred to as “cold” abscesses because they lack the normal surrounding signs of infections such as warmth and redness. Abscesses may also be found on the bone behind the ear (mastoid), joints, gums, air passages in the lungs (bronchi), and in the lungs themselves. Individuals with AR-HIES also develop recurrent lung infections (pneumonia). Pneumonia is often associated with fluid accumulation around the lungs (pleural effusion) or pus in the area between the outer surface of the lung and the chest wall (empyema). Individuals with AR-HIES may develop repeated episodes of respiratory (bronchitis), sinus (sinusitis), and middle ear infections (otitis media). Skin infections associated with AR-HIES are most often caused by Staphylococcus aureus. Pneumonia and respiratory infections associated with AR-HIES are mainly due to a wide spectrum of gram-positive and gram-negative bacteria and fungi including Streptococcus pneumoniae, Haemophilus influenzae, Pneumocystis jirovecii and Histoplasma capsulaum. In addition to bacterial infections, individuals with AR-HIES are especially susceptible to viral infections such as herpes simplex (HSV) and herpes zoster (VZV), molluscum contagiosum (MCV) and human papillomavirus (HPV). These infections which are extensive, difficult to control and mutilating, often occur concurrently.Affected individuals have developed chronic orolabial or ulcerative anogenital infections with herpes simplex virus. Eczema herpeticum as well as inflammation of the cornea (keratitis) with herpes virus also occur. Some individuals with AR-HIES have developed a severe viral skin infection known as Molluscum contagiosum caused by the molluscum contagiosum virus (MCV). This infection is characterized by raised bumps or growths (nodules) on the skin that often become red or inflamed. Nodules may be tender and itchy as well. Repeated infections with the varicella zoster virus, the virus that causes chickenpox, have also been reported in literature.In addition to susceptibility to infection, individuals with AR-HIES can present a variety of neurological symptoms. Such symptoms include partial facial paralysis, tissue degeneration due to lack of blood flow (ischemic infarction), inflammation of blood vessels (vasculitis) of the brain, and paralysis on one side of the body (hemiplegia). Neurological symptoms may progress to cause life-threatening complications including bleeding (hemorrhaging) in the brain or widening or bulging of the wall of a brain artery or vein (aneurysm). Individuals with AR-HIES may also be prone to developing autoimmune disorders such as hemolytic anemia. The term autoimmune refers to conditions in which the body's natural defenses against invading microorganisms mistakenly attack healthy tissue. Hemolytic anemia is characterized by the premature destruction of red blood cells faster than they can be reproduced. Anemia may result in fatigue, paleness, rapid heartbeat, shortness of breath, dark urine, and chills.Unlike the more common AD-HIES, 50-70% of patients with AR-HIES develop severe allergies, including anaphylaxis to food and environmental antigens, and about 30% have asthma. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_2 | Causes of Autosomal Recessive Hyper IgE Syndrome | AR-HIES is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females. All individuals, even healthy ones, carry abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. Many patients with AR-HIES were from consanguineous parents. Mutations of the dedicator of cytokinesis 8 (DOCK8) gene located on chromosome 9p are responsible for many, although not all, cases of autosomal-recessive hyper-IgE syndrome. Since the discovery that loss-of-function mutations in DOCK8 underlie AR-HIES in 2009, an estimated more than 100 patients worldwide have been identified. DOCK8 is involved in the regulation of cell migration, morphology, adhesion, and growth and is highly expressed within the immune system, suggesting crucial functions in these cell types. | Causes of Autosomal Recessive Hyper IgE Syndrome. AR-HIES is inherited as an autosomal recessive trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females. All individuals, even healthy ones, carry abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder. Many patients with AR-HIES were from consanguineous parents. Mutations of the dedicator of cytokinesis 8 (DOCK8) gene located on chromosome 9p are responsible for many, although not all, cases of autosomal-recessive hyper-IgE syndrome. Since the discovery that loss-of-function mutations in DOCK8 underlie AR-HIES in 2009, an estimated more than 100 patients worldwide have been identified. DOCK8 is involved in the regulation of cell migration, morphology, adhesion, and growth and is highly expressed within the immune system, suggesting crucial functions in these cell types. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_3 | Affects of Autosomal Recessive Hyper IgE Syndrome | AR-HIES affects males and females in equal numbers. These disorders may often go unrecognized or misdiagnosed, making it difficult to determine their true frequency in the general population. Although AR-HIES is present during infancy, diagnosis may not be made until adolescence and, in some cases, adulthood. | Affects of Autosomal Recessive Hyper IgE Syndrome. AR-HIES affects males and females in equal numbers. These disorders may often go unrecognized or misdiagnosed, making it difficult to determine their true frequency in the general population. Although AR-HIES is present during infancy, diagnosis may not be made until adolescence and, in some cases, adulthood. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_4 | Related disorders of Autosomal Recessive Hyper IgE Syndrome | Symptoms of the following disorders can be similar to those of AR-HIES. Comparisons may be useful for a differential diagnosis. Autosomal dominant hyper IgE syndrome (AD-HIES) is a rare primary immunodeficiency disorder. Like AR-HIES, it is associated with recurrent bacterial skin and lung infections. However, viral infections rarely occur. Individuals with AD-HIES also have characteristic facial features and various skeletal abnormalities including abnormal curvature of the spine (scoliosis) and repeated fractures of the long bones and ribs. Central nervous system abnormalities occur far less frequently in AD-HIES than AR-HIES and are less severe when they do. In 70% of patients, the phenotype of AD-HIES is associated with heterozygous mutations of the signal transducer and activator of transcription 3 gene (STAT3). STAT3 plays a key role in the signal transduction of a broad range of cytokines (control of infections caused by fungi and extracellular bacteria). The etiology in the remaining 30% is unknown. Most cases of AD-HIES occur randomly as the result of a spontaneous genetic change (sporadically). (For more information on this disorder, choose “autosomal dominant hyper-IgE” as your search term in the Rare Disease Database.) TYK2 deficiency was reported in one individual whose clinical symptoms were similar to AR-HIES. In the November 2006 issue of Immunity, Mineshegi et al. reported on a patient with symptoms that were very similar to those associated with AR-HIES. The patient was identified to have mutations in the TYK2 gene. Mineshegi et al. concluded that mutations in the TYK2 gene caused some cases of AR-HIES. However, in the May 2007 issue of Immunity, Woellner et al. determined that mutations in the TYK2 gene are not a common cause of AR-HIES. The authors studied several members from 15 different families with AR-HIES and did not find any mutations in the TYK2 gene. Woellner et al. concluded that TYK2 deficiency more likely represented a distinct, yet similar, immunodeficiency disorder. Atopic dermatitis is a chronic (long-lasting) disease that affects the skin. Dermatitis means inflammation of the skin and atopic refers to a group of diseases that are hereditary and often occur together. In atopic dermatitis, the skin becomes extremely itchy and inflamed causing redness, swelling, cracking, weeping, crusting, and scaling. Atopic dermatitis most often affects infants and young children, but it can continue into adulthood or first show up later in life. In most cases, there are periods of time when the disease is worse, called exacerbations or flares, followed by periods when the skin improves or clears up entirely, called remissions. Many children with atopic dermatitis will experience a permanent remission of the disease when they get older, although their skin often remains dry and easily irritated. Environmental factors can bring on symptoms of atopic dermatitis at any time in the lives of individuals who have inherited the atopic disease trait. Atopic dermatitis is often referred to as eczema, which is a general term for the many types of dermatitis. Atopic dermatitis is the most common of the many types of eczema. The cause of atopic dermatitis is unknown, although malfunction of the immune system plays a role. (For more information on this disorder, choose “atopic dermatitis” as your search term in the Rare Disease Database.) Hypereosinophilic syndrome is a rare group of disorders characterized by abnormally high levels of certain white blood cells (eosinophils) are found in the body (eosinophilia) that occurs with no identifiable cause (idiopathic). Hypereosinophilic syndrome may not be associated with any symptoms (asymptomatic) or it can damage multiple organ systems of the body. General symptoms that may be associated with include fatigue, coughing, fever, muscle pain (myalgia), and breathlessness. Some affected individuals may develop a rash and itchiness (pruritis). Additional symptoms depend upon the specific organ systems involved. Hypereosinophilic syndrome occurs with greater frequency in men than women. | Related disorders of Autosomal Recessive Hyper IgE Syndrome. Symptoms of the following disorders can be similar to those of AR-HIES. Comparisons may be useful for a differential diagnosis. Autosomal dominant hyper IgE syndrome (AD-HIES) is a rare primary immunodeficiency disorder. Like AR-HIES, it is associated with recurrent bacterial skin and lung infections. However, viral infections rarely occur. Individuals with AD-HIES also have characteristic facial features and various skeletal abnormalities including abnormal curvature of the spine (scoliosis) and repeated fractures of the long bones and ribs. Central nervous system abnormalities occur far less frequently in AD-HIES than AR-HIES and are less severe when they do. In 70% of patients, the phenotype of AD-HIES is associated with heterozygous mutations of the signal transducer and activator of transcription 3 gene (STAT3). STAT3 plays a key role in the signal transduction of a broad range of cytokines (control of infections caused by fungi and extracellular bacteria). The etiology in the remaining 30% is unknown. Most cases of AD-HIES occur randomly as the result of a spontaneous genetic change (sporadically). (For more information on this disorder, choose “autosomal dominant hyper-IgE” as your search term in the Rare Disease Database.) TYK2 deficiency was reported in one individual whose clinical symptoms were similar to AR-HIES. In the November 2006 issue of Immunity, Mineshegi et al. reported on a patient with symptoms that were very similar to those associated with AR-HIES. The patient was identified to have mutations in the TYK2 gene. Mineshegi et al. concluded that mutations in the TYK2 gene caused some cases of AR-HIES. However, in the May 2007 issue of Immunity, Woellner et al. determined that mutations in the TYK2 gene are not a common cause of AR-HIES. The authors studied several members from 15 different families with AR-HIES and did not find any mutations in the TYK2 gene. Woellner et al. concluded that TYK2 deficiency more likely represented a distinct, yet similar, immunodeficiency disorder. Atopic dermatitis is a chronic (long-lasting) disease that affects the skin. Dermatitis means inflammation of the skin and atopic refers to a group of diseases that are hereditary and often occur together. In atopic dermatitis, the skin becomes extremely itchy and inflamed causing redness, swelling, cracking, weeping, crusting, and scaling. Atopic dermatitis most often affects infants and young children, but it can continue into adulthood or first show up later in life. In most cases, there are periods of time when the disease is worse, called exacerbations or flares, followed by periods when the skin improves or clears up entirely, called remissions. Many children with atopic dermatitis will experience a permanent remission of the disease when they get older, although their skin often remains dry and easily irritated. Environmental factors can bring on symptoms of atopic dermatitis at any time in the lives of individuals who have inherited the atopic disease trait. Atopic dermatitis is often referred to as eczema, which is a general term for the many types of dermatitis. Atopic dermatitis is the most common of the many types of eczema. The cause of atopic dermatitis is unknown, although malfunction of the immune system plays a role. (For more information on this disorder, choose “atopic dermatitis” as your search term in the Rare Disease Database.) Hypereosinophilic syndrome is a rare group of disorders characterized by abnormally high levels of certain white blood cells (eosinophils) are found in the body (eosinophilia) that occurs with no identifiable cause (idiopathic). Hypereosinophilic syndrome may not be associated with any symptoms (asymptomatic) or it can damage multiple organ systems of the body. General symptoms that may be associated with include fatigue, coughing, fever, muscle pain (myalgia), and breathlessness. Some affected individuals may develop a rash and itchiness (pruritis). Additional symptoms depend upon the specific organ systems involved. Hypereosinophilic syndrome occurs with greater frequency in men than women. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_5 | Diagnosis of Autosomal Recessive Hyper IgE Syndrome | Due to the great variety of clinical features of AR-HIES early diagnosis can be challenging and genetic testing for DOCK8 deficiency may be essential.A diagnosis of AR-HIES is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. Laboratory studies that may aid in a diagnosis include blood tests that demonstrate elevated levels of IgE in the blood and elevated levels of certain white blood cells known as eosinophils (eosinophilia).X-ray studies such as computed tomography (CT scanning) may be used to detect lung infections. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. | Diagnosis of Autosomal Recessive Hyper IgE Syndrome. Due to the great variety of clinical features of AR-HIES early diagnosis can be challenging and genetic testing for DOCK8 deficiency may be essential.A diagnosis of AR-HIES is made based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. Laboratory studies that may aid in a diagnosis include blood tests that demonstrate elevated levels of IgE in the blood and elevated levels of certain white blood cells known as eosinophils (eosinophilia).X-ray studies such as computed tomography (CT scanning) may be used to detect lung infections. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_133_6 | Therapies of Autosomal Recessive Hyper IgE Syndrome | TreatmentThe treatment of AR-HIES is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dermatologists, pneumologists, immunologists, and other health care professionals may need to systematically and comprehensively plan an affect child's treatment.The therapeutic approach involves prevention and management of infections. Long-term administration of systemic antibiotics and antiviral drugs is recommended.The mainstay for treatment of individuals with AR-HIES is preventative (prophylactic) antibiotic therapy against bacterial infection. Common antibiotic medications (e.g., anti-staphylococcal agents) used to treat individuals with AR-HIES include dicloxacillin, trimethoprim-sulfamethooxazole, cephalosporin, cotrimoxazole, and penicillin.Surgical drainage of existing skin lesions, followed by a regimen of antibiotic therapy may be required in some cases. Topical steroids and moisturizing creams may also be used to treat skin lesions.Genetic counseling may be of benefit for affected individuals and their families. | Therapies of Autosomal Recessive Hyper IgE Syndrome. TreatmentThe treatment of AR-HIES is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, dermatologists, pneumologists, immunologists, and other health care professionals may need to systematically and comprehensively plan an affect child's treatment.The therapeutic approach involves prevention and management of infections. Long-term administration of systemic antibiotics and antiviral drugs is recommended.The mainstay for treatment of individuals with AR-HIES is preventative (prophylactic) antibiotic therapy against bacterial infection. Common antibiotic medications (e.g., anti-staphylococcal agents) used to treat individuals with AR-HIES include dicloxacillin, trimethoprim-sulfamethooxazole, cephalosporin, cotrimoxazole, and penicillin.Surgical drainage of existing skin lesions, followed by a regimen of antibiotic therapy may be required in some cases. Topical steroids and moisturizing creams may also be used to treat skin lesions.Genetic counseling may be of benefit for affected individuals and their families. | 133 | Autosomal Recessive Hyper IgE Syndrome |
nord_134_0 | Overview of Autosomal Recessive Hypophosphatemic Rickets Type 2 | SummaryAutosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a skeletal condition that is characterized by rickets, bone pain, bone deformities, increased risk of bone fractures, fatigue, short stature and calcium deposits in the sites where ligaments and tendons attach to the bones (calcific enthesopathy).ARHR2 is an extremely rare condition, characterized by low phosphate levels in the blood (hypophosphatemia) resulting from renal phosphate wasting. ARHR2 affects males and females equally and occurs in populations all around the world. ARHR2 can develop at any time in childhood or adolescence. The manifestations of ARHR2 can vary widely, even among members of the same family. The prevalence of ARHR2 is unknown.ARHR2 is caused by changes (variants) in the ENPP1 gene and is thus part of ENPP1 deficiency. Depending on age, ENPP1 deficiency can manifest in two different presentations (phenotypes): ARHR2 and generalized arterial calcification of infancy (GACI) type 1. GACI type 1 causes pathological soft tissue calcification, including mineralization of the arteries, heart, kidneys and joints. Most infants with ENPP1 deficiency who survive GACI type 1 will develop ARHR2, although ARHR2 can also be seen in patients without a prior history of GACI.ARHR2 is treated with daily phosphorus and active vitamin D supplementation. The phosphorus is typically taken every four to six hours to maintain proper levels in the body. Regular blood and urine tests are required to ensure the correct balance is achieved. Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain. | Overview of Autosomal Recessive Hypophosphatemic Rickets Type 2. SummaryAutosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a skeletal condition that is characterized by rickets, bone pain, bone deformities, increased risk of bone fractures, fatigue, short stature and calcium deposits in the sites where ligaments and tendons attach to the bones (calcific enthesopathy).ARHR2 is an extremely rare condition, characterized by low phosphate levels in the blood (hypophosphatemia) resulting from renal phosphate wasting. ARHR2 affects males and females equally and occurs in populations all around the world. ARHR2 can develop at any time in childhood or adolescence. The manifestations of ARHR2 can vary widely, even among members of the same family. The prevalence of ARHR2 is unknown.ARHR2 is caused by changes (variants) in the ENPP1 gene and is thus part of ENPP1 deficiency. Depending on age, ENPP1 deficiency can manifest in two different presentations (phenotypes): ARHR2 and generalized arterial calcification of infancy (GACI) type 1. GACI type 1 causes pathological soft tissue calcification, including mineralization of the arteries, heart, kidneys and joints. Most infants with ENPP1 deficiency who survive GACI type 1 will develop ARHR2, although ARHR2 can also be seen in patients without a prior history of GACI.ARHR2 is treated with daily phosphorus and active vitamin D supplementation. The phosphorus is typically taken every four to six hours to maintain proper levels in the body. Regular blood and urine tests are required to ensure the correct balance is achieved. Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_1 | Symptoms of Autosomal Recessive Hypophosphatemic Rickets Type 2 | Bone deformity, bone pain, increased risk of bone fractures and short stature are symptoms of ARHR2. The most noticeable bone changes are bowed legs (genu varum) or knock knees (genu valgum), but bone changes in the s ribs and other parts of the body can also be the result of ARHR2. All bones in the body can be affected by ARHR2.ARHR2 doesn’t always present with the typical X-ray features of rickets, and diagnosis can be confirmed by a blood test that shows low levels of phosphate (hypophosphatemia) and elevated alkaline phosphatase and FGF23, in the setting of ENPP1 variants. Patients also have too much phosphate in their urine (hyperphosphaturia) due to renal phosphate wasting.Over-retained primary teeth, teeth that don’t fully erupt (infraocclusion), increased cementum, ankylosis, and slow orthodontic movement are also possible symptoms of ENPP1 deficiency.Calcium deposits that develop in the sites where ligaments and tendons attach to the bones (calcific enthesopathies) can also be a symptom of ARHR2 in later life. This may be inflammatory and can cause pain in the area it affects. | Symptoms of Autosomal Recessive Hypophosphatemic Rickets Type 2. Bone deformity, bone pain, increased risk of bone fractures and short stature are symptoms of ARHR2. The most noticeable bone changes are bowed legs (genu varum) or knock knees (genu valgum), but bone changes in the s ribs and other parts of the body can also be the result of ARHR2. All bones in the body can be affected by ARHR2.ARHR2 doesn’t always present with the typical X-ray features of rickets, and diagnosis can be confirmed by a blood test that shows low levels of phosphate (hypophosphatemia) and elevated alkaline phosphatase and FGF23, in the setting of ENPP1 variants. Patients also have too much phosphate in their urine (hyperphosphaturia) due to renal phosphate wasting.Over-retained primary teeth, teeth that don’t fully erupt (infraocclusion), increased cementum, ankylosis, and slow orthodontic movement are also possible symptoms of ENPP1 deficiency.Calcium deposits that develop in the sites where ligaments and tendons attach to the bones (calcific enthesopathies) can also be a symptom of ARHR2 in later life. This may be inflammatory and can cause pain in the area it affects. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_2 | Causes of Autosomal Recessive Hypophosphatemic Rickets Type 2 | ARHR2 is caused by variants in the ENPP1 gene and is also known as ENPP1 deficiency. ENPP1 encodes a protein called ectonucleotide pyrophosphatase / phosphodiesterase 1 (NPP1), which is a major generator of extracellular pyrophosphate (PPi). Because PPi inhibits calcification, two inactivating variants in the ENPP1 gene are also responsible for GACI type 1.In patients with ARHR2, high circulating levels of FGF23 have been described. FGF23 is a secreted protein, which reduces the activity of sodium-phosphate co-transporters NPT2a and NPT2c resulting in renal phosphate wasting, diminishes the renal 1α-hydroxylase, and increases the 24-hydroxylase activity. Moreover, FGF23 acts at the parathyroid gland to decrease parathyroid hormone synthesis and secretion. Currently, it is unclear how variants in the ENPP1 gene result in high FGF23 levels.Some researchers hypothesize that patients with ENPP1 deficiency develop a state of low phosphate in their serum, known as hypophosphatemia, as a compensatory mechanism for the state of low PPi in order to inhibit or decrease ectopic calcification. This hypophosphatemia leads to rickets in affected patients.ARHR2 is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. | Causes of Autosomal Recessive Hypophosphatemic Rickets Type 2. ARHR2 is caused by variants in the ENPP1 gene and is also known as ENPP1 deficiency. ENPP1 encodes a protein called ectonucleotide pyrophosphatase / phosphodiesterase 1 (NPP1), which is a major generator of extracellular pyrophosphate (PPi). Because PPi inhibits calcification, two inactivating variants in the ENPP1 gene are also responsible for GACI type 1.In patients with ARHR2, high circulating levels of FGF23 have been described. FGF23 is a secreted protein, which reduces the activity of sodium-phosphate co-transporters NPT2a and NPT2c resulting in renal phosphate wasting, diminishes the renal 1α-hydroxylase, and increases the 24-hydroxylase activity. Moreover, FGF23 acts at the parathyroid gland to decrease parathyroid hormone synthesis and secretion. Currently, it is unclear how variants in the ENPP1 gene result in high FGF23 levels.Some researchers hypothesize that patients with ENPP1 deficiency develop a state of low phosphate in their serum, known as hypophosphatemia, as a compensatory mechanism for the state of low PPi in order to inhibit or decrease ectopic calcification. This hypophosphatemia leads to rickets in affected patients.ARHR2 is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_3 | Affects of Autosomal Recessive Hypophosphatemic Rickets Type 2 | ARHR2 affects males and females equally and occurs in populations all across the world. The manifestations of ARHR2 can vary widely, even among members of the same family. ARHR2 can affect patients of any age but symptoms are most likely to appear in childhood. ARHR2 is caused by ENPP1 deficiency and occurs in 1:200,000 pregnancies. | Affects of Autosomal Recessive Hypophosphatemic Rickets Type 2. ARHR2 affects males and females equally and occurs in populations all across the world. The manifestations of ARHR2 can vary widely, even among members of the same family. ARHR2 can affect patients of any age but symptoms are most likely to appear in childhood. ARHR2 is caused by ENPP1 deficiency and occurs in 1:200,000 pregnancies. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_4 | Related disorders of Autosomal Recessive Hypophosphatemic Rickets Type 2 | Generalized arterial calcification of infancy (GACI) is a rare genetic disorder that affects the circulatory system in addition to other body systems. It occurs in approximately 1:200,000 pregnancies. GACI affects males and females equally and occurs in populations all around the world. GACI has an autosomal recessive inheritance pattern and usually affects infants during the first 6 months of life. Symptoms of GACI include respiratory distress, arterial calcification, gastrointestinal issues, joint calcification, hearing loss, high blood pressure, stroke, reduced or absent pulses, and heart failure. GACI manifests itself differently even within families with the same genetic cause of the disease. No two people with GACI will have identical medical characteristics. (For more information on this condition search for “GACI” in the Rare Disease Database.)Autosomal recessive hypophosphatemic rickets type 1 (ARHR1) is caused by homozygous loss-of-function variants in the DMP1 gene. DMP1 is a non-collagenous extracellular protein, highly expressed in osteoblasts and osteocytes in bone and teeth. It plays critical roles in bone mineralization, phosphate homeostasis and odontogenic differentiation. Symptoms include short stature, limited movement of spine and hip, calcification of the ligaments at the bony insertion sites and high bone density at the base of skull, clavicle and rib anomalies.Familial hypophosphatemia is a term that describes a group of rare inherited disorders characterized by impaired kidney conservation of phosphate and in some cases, altered vitamin D metabolism. In contrast, other forms of hypophosphatemia may result from inadequate dietary supply of phosphate, or its poor absorption from the intestines. The chronic hypophosphatemia resulting from these impairments can lead to rickets, a childhood bone disease with characteristic bow deformities of the legs, or a progressive softening of the bon in adulthood, referred to as osteomalacia. In children, growth rates may be impaired, frequently resulting in short stature. In adults, the growth plate is not present so osteomalacia is the evident bone problem. Familial hypophosphatemia is most often inherited in an X-linked dominant manner; however, autosomal dominant and recessive forms of familial hypophosphatemia occur. (For more information on this condition search for “familial hypophosphatemia” in the Rare Disease Database.) | Related disorders of Autosomal Recessive Hypophosphatemic Rickets Type 2. Generalized arterial calcification of infancy (GACI) is a rare genetic disorder that affects the circulatory system in addition to other body systems. It occurs in approximately 1:200,000 pregnancies. GACI affects males and females equally and occurs in populations all around the world. GACI has an autosomal recessive inheritance pattern and usually affects infants during the first 6 months of life. Symptoms of GACI include respiratory distress, arterial calcification, gastrointestinal issues, joint calcification, hearing loss, high blood pressure, stroke, reduced or absent pulses, and heart failure. GACI manifests itself differently even within families with the same genetic cause of the disease. No two people with GACI will have identical medical characteristics. (For more information on this condition search for “GACI” in the Rare Disease Database.)Autosomal recessive hypophosphatemic rickets type 1 (ARHR1) is caused by homozygous loss-of-function variants in the DMP1 gene. DMP1 is a non-collagenous extracellular protein, highly expressed in osteoblasts and osteocytes in bone and teeth. It plays critical roles in bone mineralization, phosphate homeostasis and odontogenic differentiation. Symptoms include short stature, limited movement of spine and hip, calcification of the ligaments at the bony insertion sites and high bone density at the base of skull, clavicle and rib anomalies.Familial hypophosphatemia is a term that describes a group of rare inherited disorders characterized by impaired kidney conservation of phosphate and in some cases, altered vitamin D metabolism. In contrast, other forms of hypophosphatemia may result from inadequate dietary supply of phosphate, or its poor absorption from the intestines. The chronic hypophosphatemia resulting from these impairments can lead to rickets, a childhood bone disease with characteristic bow deformities of the legs, or a progressive softening of the bon in adulthood, referred to as osteomalacia. In children, growth rates may be impaired, frequently resulting in short stature. In adults, the growth plate is not present so osteomalacia is the evident bone problem. Familial hypophosphatemia is most often inherited in an X-linked dominant manner; however, autosomal dominant and recessive forms of familial hypophosphatemia occur. (For more information on this condition search for “familial hypophosphatemia” in the Rare Disease Database.) | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_5 | Diagnosis of Autosomal Recessive Hypophosphatemic Rickets Type 2 | If a patient with GACI type 1 is having regular blood tests, the signs of ARHR2 may be identified long before any bone abnormalities or bone pain have appeared. A blood test that shows low levels of phosphate and high levels of alkaline phosphatase can be indicators of ARHR2.If there is no history of GACI type 1, ARHR2 should be considered in patients presenting with bone deformities, frequent bone fractures, and bone pain. ARHR2 doesn’t always present with the typical X-ray features of rickets, and diagnosis can be confirmed by a blood test that shows low levels of phosphate (hypophosphatemia) and elevated alkaline phosphatase and FGF23 in the setting of ENPP1 deficiency. Patients also have too much phosphate in their urine (hyperphosphaturia) due to renal phosphate wasting.To confirm an ARHR2 diagnosis the patient (and sometimes parents) may be genetically tested for variants in the ENPP1 gene.Medical Monitoring
Ongoing monitoring of ARHR2 includes ultrasounds, X-rays, frequent lab and urine work, orthopedic evaluation/ intervention and physical therapy.Significant improvement in symptoms can be achieved if corrective action is taken while the bones are still actively growing. Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain.Potential side effects of phosphorus supplementation can include gastrointestinal upset, diarrhea and nausea. Patients should also be monitored via kidney ultrasound as a build-up of calcium in the kidneys (nephrocalcinosis) is another possible side effect of phosphate supplementation. | Diagnosis of Autosomal Recessive Hypophosphatemic Rickets Type 2. If a patient with GACI type 1 is having regular blood tests, the signs of ARHR2 may be identified long before any bone abnormalities or bone pain have appeared. A blood test that shows low levels of phosphate and high levels of alkaline phosphatase can be indicators of ARHR2.If there is no history of GACI type 1, ARHR2 should be considered in patients presenting with bone deformities, frequent bone fractures, and bone pain. ARHR2 doesn’t always present with the typical X-ray features of rickets, and diagnosis can be confirmed by a blood test that shows low levels of phosphate (hypophosphatemia) and elevated alkaline phosphatase and FGF23 in the setting of ENPP1 deficiency. Patients also have too much phosphate in their urine (hyperphosphaturia) due to renal phosphate wasting.To confirm an ARHR2 diagnosis the patient (and sometimes parents) may be genetically tested for variants in the ENPP1 gene.Medical Monitoring
Ongoing monitoring of ARHR2 includes ultrasounds, X-rays, frequent lab and urine work, orthopedic evaluation/ intervention and physical therapy.Significant improvement in symptoms can be achieved if corrective action is taken while the bones are still actively growing. Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain.Potential side effects of phosphorus supplementation can include gastrointestinal upset, diarrhea and nausea. Patients should also be monitored via kidney ultrasound as a build-up of calcium in the kidneys (nephrocalcinosis) is another possible side effect of phosphate supplementation. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_134_6 | Therapies of Autosomal Recessive Hypophosphatemic Rickets Type 2 | Treatment
ARHR2 is treated with daily phosphorus and active vitamin D supplementation which maintains proper levels in the body as determined by regular blood and urine tests. Phosphorus is typically taken every four to six hours to maintain proper levels in the body. Even with treatment, patients will continue to waste phosphate through their urine, but the frequent medication administration replaces the lost phosphate.Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain. If bone deformities are not corrected at a young age through medication, surgical intervention may be required. There are two possible options for surgery to correct deformities of the legs – eight-plate surgery (also known as guided growth) and bone realignment surgery (osteotomy).Patients with ARHR2 are usually followed by a team of specialists which may include endocrinology, nephrology, orthopedics, physical therapy, dental, and audiology. | Therapies of Autosomal Recessive Hypophosphatemic Rickets Type 2. Treatment
ARHR2 is treated with daily phosphorus and active vitamin D supplementation which maintains proper levels in the body as determined by regular blood and urine tests. Phosphorus is typically taken every four to six hours to maintain proper levels in the body. Even with treatment, patients will continue to waste phosphate through their urine, but the frequent medication administration replaces the lost phosphate.Early diagnosis and prompt treatment can help prevent/correct bone deformities and relieve bone pain. If bone deformities are not corrected at a young age through medication, surgical intervention may be required. There are two possible options for surgery to correct deformities of the legs – eight-plate surgery (also known as guided growth) and bone realignment surgery (osteotomy).Patients with ARHR2 are usually followed by a team of specialists which may include endocrinology, nephrology, orthopedics, physical therapy, dental, and audiology. | 134 | Autosomal Recessive Hypophosphatemic Rickets Type 2 |
nord_135_0 | Overview of Autosomal Recessive Polycystic Kidney Disease | Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the formation of fluid-filled sacs (cysts) in the kidneys. Most affected infants have enlarged kidneys during the newborn (neonatal) period and some cases may be fatal at this time. ARPKD is not simply a kidney disease and additional organ systems of the body may also be affected, especially the liver. High blood pressure (hypertension), excessive thirst, frequent urination and feeding difficulties may also occur. Some affected children may also have distinctive facial features and incomplete development of the lungs (pulmonary hypoplasia) causing breathing (respiratory) difficulties. The severity of the disorder and the specific symptoms that occur can vary greatly from one person to another. Some affected children eventually develop end-stage renal disease sometime during the first decade of life. In some patients, symptoms do not develop until adolescence or even adulthood. ARPKD is caused by changes (mutations) in the PKHD1 gene. | Overview of Autosomal Recessive Polycystic Kidney Disease. Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the formation of fluid-filled sacs (cysts) in the kidneys. Most affected infants have enlarged kidneys during the newborn (neonatal) period and some cases may be fatal at this time. ARPKD is not simply a kidney disease and additional organ systems of the body may also be affected, especially the liver. High blood pressure (hypertension), excessive thirst, frequent urination and feeding difficulties may also occur. Some affected children may also have distinctive facial features and incomplete development of the lungs (pulmonary hypoplasia) causing breathing (respiratory) difficulties. The severity of the disorder and the specific symptoms that occur can vary greatly from one person to another. Some affected children eventually develop end-stage renal disease sometime during the first decade of life. In some patients, symptoms do not develop until adolescence or even adulthood. ARPKD is caused by changes (mutations) in the PKHD1 gene. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_1 | Symptoms of Autosomal Recessive Polycystic Kidney Disease | The severity and progression of ARPKD can vary greatly from one person to another, even among members of the same family. In severe cases, ARPKD can cause life-threatening complications during infancy. In other cases, affected individuals may not develop symptoms until later during childhood or adolescence. Some children may need a kidney (renal) transplant early in childhood; others may not need a transplant until early adulthood, or not at all. In rare cases, individuals may not develop symptoms until young adulthood. Generally, individuals who develop ARPKD later in life have milder kidney disease, but more severe liver disease.Most of the medical literature on ARPKD, especially those written before the identification of the ARPKD disease gene, disproportionately focused on the most severe cases. Therefore, much of the literature may give the incorrect impression that ARPKD is a uniformly fatal or debilitating disease. Researchers now know that ARPKD can range from mild to severe. Consequently, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.The characteristic finding of ARPKD is the development of fluid-filled sacs (cysts) in the kidneys. All affected individuals develop cysts in the kidneys, but the number, size, progression and severity of cyst development varies greatly from one person to another. In most affected individuals, renal cysts grow and multiply in utero causing abnormal enlargement of the kidneys. Enlarged kidneys may be apparent at birth or during the newborn period. In these infants, the kidneys are firm and can be felt (palpated) in both flanks. Additional symptoms associated with cystic kidneys include high blood pressure (hypertension) and flank pain. High blood pressure is common in children with ARPKD and can be widespread, severe and difficult to manage.In severe cases of ARPKD, affected infants may face life-threatening complications shortly after birth, especially breathing (respiratory) insufficiency or failure. Breathing difficulties usually occur due to deficient levels of amniotic fluid (oligohydramnios) during pregnancy. Massively enlarged kidneys, which prevent the proper development of the lungs, may also contribute to respiratory insufficiency or failure. Although some children do not survive the newborn period (approximately 30 percent by most estimates), the majority of children survive.Children who survive beyond the newborn period usually develop worsening kidney function, although the kidneys may reduce in size. Most children do not develop chronic renal insufficiency until late childhood, adolescence or young adulthood. Renal insufficiency refers to the impaired ability of the kidneys to perform their basic functions. The kidneys are two bean-shaped organs located under the ribcage. The kidneys have several functions including filtering and excreting waste products from the blood and body, creating certain hormones, and helping maintain the balance of certain chemicals in the body such as potassium, sodium, chloride, calcium and other electrolytes. Damage to the kidneys in ARPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, excessive thirst and frequent urination. Eventually, many children progress to end-stage renal disease.In severe cases of ARPKD, affected infants have extremely enlarged kidneys and decreased urine production at birth. Decreased urine production in utero contributes to a deficiency of amniotic fluid (oligohydramnios), the fluid that surrounds a developing fetus. In addition to protecting and cushioning a fetus, amniotic fluid contains growth factors and other substances that are vital to fetal development. Low amniotic fluid levels can impair lung development and, consequently, some affected infants may have underdeveloped lungs (pulmonary hypoplasia). These infants can experience severe, life-threatening breathing (respiratory) complications during the newborn period. Infants with oligohydramnios may also develop distinctive facial features including deep-set eyes, a flattened nose, a small jaw (micrognathia), and abnormal, low-set ears. The physical findings associated with oligohydramnios are sometimes referred to as Potter’s sequence.In addition to the kidneys, the liver is also commonly affected in children and adults with ARPKD. The liver performs many functions in the body including converting food into energy and nutrients, storing vitamins, and filtering toxins from the body. Children with ARPKD develop a liver condition known as congenital hepatic fibrosis, in which excess fiber-like connective tissue spreads throughout the liver. Although all children have congenital hepatic fibrosis, not all children develop liver dysfunction. Liver abnormalities that can occur in ARPKD include enlargement of the liver (hepatomegaly), inflammation and infection of the tubes (bile ducts) that carry bile from the liver to the gallbladder and intestines (cholangitis), and high blood pressure of the main vein of the liver (portal hypertension).Portal hypertension can cause increased pressure and swelling (distention) of veins (varices) of the esophagus, the stomach and intestines. These veins can rupture and potentially cause life-threatening gastrointestinal bleeding (variceal bleeding). Affected children may experience progressive liver dysfunction and scarring (cirrhosis) and ultimately liver failure.Children with ARPKD may also experience feeding difficulties due to poor kidney function or from compression of the stomach by enlarged kidneys, liver and/or spleen. Feeding difficulties and chronic renal failure may contribute to poor growth in affected individuals. Some children may be prone to urinary tract infections and have problems with water and salt balance.Some children with ARPKD may also experience enlargement of the spleen (splenomegaly). Splenomegaly can potentially result in low levels of red blood cells (anemia), platelets (thrombocytopenia) and white blood cells (leukopenia). Anemia can cause fatigue, pale skin, irregular heartbeat, and shortness of breath. Thrombocytopenia can result in easy bruising, prolonged bleeding from cuts, spontaneous nosebleeds, and superficial bleeding in the skin (petechiae). Leukopenia decreases the body’s ability to fight infection and disease. | Symptoms of Autosomal Recessive Polycystic Kidney Disease. The severity and progression of ARPKD can vary greatly from one person to another, even among members of the same family. In severe cases, ARPKD can cause life-threatening complications during infancy. In other cases, affected individuals may not develop symptoms until later during childhood or adolescence. Some children may need a kidney (renal) transplant early in childhood; others may not need a transplant until early adulthood, or not at all. In rare cases, individuals may not develop symptoms until young adulthood. Generally, individuals who develop ARPKD later in life have milder kidney disease, but more severe liver disease.Most of the medical literature on ARPKD, especially those written before the identification of the ARPKD disease gene, disproportionately focused on the most severe cases. Therefore, much of the literature may give the incorrect impression that ARPKD is a uniformly fatal or debilitating disease. Researchers now know that ARPKD can range from mild to severe. Consequently, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.The characteristic finding of ARPKD is the development of fluid-filled sacs (cysts) in the kidneys. All affected individuals develop cysts in the kidneys, but the number, size, progression and severity of cyst development varies greatly from one person to another. In most affected individuals, renal cysts grow and multiply in utero causing abnormal enlargement of the kidneys. Enlarged kidneys may be apparent at birth or during the newborn period. In these infants, the kidneys are firm and can be felt (palpated) in both flanks. Additional symptoms associated with cystic kidneys include high blood pressure (hypertension) and flank pain. High blood pressure is common in children with ARPKD and can be widespread, severe and difficult to manage.In severe cases of ARPKD, affected infants may face life-threatening complications shortly after birth, especially breathing (respiratory) insufficiency or failure. Breathing difficulties usually occur due to deficient levels of amniotic fluid (oligohydramnios) during pregnancy. Massively enlarged kidneys, which prevent the proper development of the lungs, may also contribute to respiratory insufficiency or failure. Although some children do not survive the newborn period (approximately 30 percent by most estimates), the majority of children survive.Children who survive beyond the newborn period usually develop worsening kidney function, although the kidneys may reduce in size. Most children do not develop chronic renal insufficiency until late childhood, adolescence or young adulthood. Renal insufficiency refers to the impaired ability of the kidneys to perform their basic functions. The kidneys are two bean-shaped organs located under the ribcage. The kidneys have several functions including filtering and excreting waste products from the blood and body, creating certain hormones, and helping maintain the balance of certain chemicals in the body such as potassium, sodium, chloride, calcium and other electrolytes. Damage to the kidneys in ARPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, excessive thirst and frequent urination. Eventually, many children progress to end-stage renal disease.In severe cases of ARPKD, affected infants have extremely enlarged kidneys and decreased urine production at birth. Decreased urine production in utero contributes to a deficiency of amniotic fluid (oligohydramnios), the fluid that surrounds a developing fetus. In addition to protecting and cushioning a fetus, amniotic fluid contains growth factors and other substances that are vital to fetal development. Low amniotic fluid levels can impair lung development and, consequently, some affected infants may have underdeveloped lungs (pulmonary hypoplasia). These infants can experience severe, life-threatening breathing (respiratory) complications during the newborn period. Infants with oligohydramnios may also develop distinctive facial features including deep-set eyes, a flattened nose, a small jaw (micrognathia), and abnormal, low-set ears. The physical findings associated with oligohydramnios are sometimes referred to as Potter’s sequence.In addition to the kidneys, the liver is also commonly affected in children and adults with ARPKD. The liver performs many functions in the body including converting food into energy and nutrients, storing vitamins, and filtering toxins from the body. Children with ARPKD develop a liver condition known as congenital hepatic fibrosis, in which excess fiber-like connective tissue spreads throughout the liver. Although all children have congenital hepatic fibrosis, not all children develop liver dysfunction. Liver abnormalities that can occur in ARPKD include enlargement of the liver (hepatomegaly), inflammation and infection of the tubes (bile ducts) that carry bile from the liver to the gallbladder and intestines (cholangitis), and high blood pressure of the main vein of the liver (portal hypertension).Portal hypertension can cause increased pressure and swelling (distention) of veins (varices) of the esophagus, the stomach and intestines. These veins can rupture and potentially cause life-threatening gastrointestinal bleeding (variceal bleeding). Affected children may experience progressive liver dysfunction and scarring (cirrhosis) and ultimately liver failure.Children with ARPKD may also experience feeding difficulties due to poor kidney function or from compression of the stomach by enlarged kidneys, liver and/or spleen. Feeding difficulties and chronic renal failure may contribute to poor growth in affected individuals. Some children may be prone to urinary tract infections and have problems with water and salt balance.Some children with ARPKD may also experience enlargement of the spleen (splenomegaly). Splenomegaly can potentially result in low levels of red blood cells (anemia), platelets (thrombocytopenia) and white blood cells (leukopenia). Anemia can cause fatigue, pale skin, irregular heartbeat, and shortness of breath. Thrombocytopenia can result in easy bruising, prolonged bleeding from cuts, spontaneous nosebleeds, and superficial bleeding in the skin (petechiae). Leukopenia decreases the body’s ability to fight infection and disease. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_2 | Causes of Autosomal Recessive Polycystic Kidney Disease | ARPKD is caused by mutations of the PKHD1 gene and is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. PKHD1 is a large gene and many different mutations to this gene cause ARPKD. The PKHD1 gene contains instructions for creating (encoding) a protein known as fibrocystin (or polyductin). If patients have two mutations that result in no protein being generated, the result is usually lethal. However, in the majority of patients at least one copy of the gene generates some functional protein and these cases are usually viable. The exact role and function of this protein in the body is unknown.The ARPKD protein may be involved in the proper development or function of cilia, a hair-like structure found on most cells in the body. Cilia are classified as motile or immotile. Motile cilia have specific mechanical functions such as to move or propel mucus over the cell in the respiratory tract, while immotile (primary) cilia were believed to play a sensory or mechano-sensory role. Immotile cilia are active structures required for normal health and development that are involved in sensing the environment outside of the cell and sending related signals into the cell. The exact relationship between the ARPKD protein and the cilia and their ultimate roles in proper kidney function and health is not fully understood. More research is necessary to determine the complex, underlying mechanisms that ultimately cause ARPKD.The symptoms of ARPKD result from the development and continued enlargement of cysts in the kidneys and other organ systems of the body. Cysts within the kidneys form within nephrons, which are small tubules that serve as the basic filtering units of the kidneys and help to remove waste from the blood. Cysts form at the tips or ends of the nephrons, a section known as the collecting tubules. Specifically, a cyst is a widened (dilated) collecting tubule that has swollen or ballooned. Because of the numerous cysts that form, the kidneys become enlarged and normal nephrons are destroyed, eventually eliminating kidney function. In a normal kidney, the nephrons and collecting tubules help to regulate the amount of water and acid in the body.The liver symptoms of ARPKD result from the improper development of the network of bile ducts found within the liver. Bile ducts may be widened (dilated) and duplicated and surrounding tissue may become inflamed, ultimately causing scarring in the affected area. This scarring process is known as congenital hepatic fibrosis. All children with ARPKD have congenital hepatic fibrosis, but not all children develop clinically evident liver disease. | Causes of Autosomal Recessive Polycystic Kidney Disease. ARPKD is caused by mutations of the PKHD1 gene and is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females. PKHD1 is a large gene and many different mutations to this gene cause ARPKD. The PKHD1 gene contains instructions for creating (encoding) a protein known as fibrocystin (or polyductin). If patients have two mutations that result in no protein being generated, the result is usually lethal. However, in the majority of patients at least one copy of the gene generates some functional protein and these cases are usually viable. The exact role and function of this protein in the body is unknown.The ARPKD protein may be involved in the proper development or function of cilia, a hair-like structure found on most cells in the body. Cilia are classified as motile or immotile. Motile cilia have specific mechanical functions such as to move or propel mucus over the cell in the respiratory tract, while immotile (primary) cilia were believed to play a sensory or mechano-sensory role. Immotile cilia are active structures required for normal health and development that are involved in sensing the environment outside of the cell and sending related signals into the cell. The exact relationship between the ARPKD protein and the cilia and their ultimate roles in proper kidney function and health is not fully understood. More research is necessary to determine the complex, underlying mechanisms that ultimately cause ARPKD.The symptoms of ARPKD result from the development and continued enlargement of cysts in the kidneys and other organ systems of the body. Cysts within the kidneys form within nephrons, which are small tubules that serve as the basic filtering units of the kidneys and help to remove waste from the blood. Cysts form at the tips or ends of the nephrons, a section known as the collecting tubules. Specifically, a cyst is a widened (dilated) collecting tubule that has swollen or ballooned. Because of the numerous cysts that form, the kidneys become enlarged and normal nephrons are destroyed, eventually eliminating kidney function. In a normal kidney, the nephrons and collecting tubules help to regulate the amount of water and acid in the body.The liver symptoms of ARPKD result from the improper development of the network of bile ducts found within the liver. Bile ducts may be widened (dilated) and duplicated and surrounding tissue may become inflamed, ultimately causing scarring in the affected area. This scarring process is known as congenital hepatic fibrosis. All children with ARPKD have congenital hepatic fibrosis, but not all children develop clinically evident liver disease. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_3 | Affects of Autosomal Recessive Polycystic Kidney Disease | ARPKD affects males and females in equal numbers. The incidence of ARPKD is estimated to occur in approximately 1 in 20,000 individuals in the general population. Approximately ~1/70 people carry a single mutation in the PKHD1 gene. Because some people may go undiagnosed, it is difficult to determine the true frequency of ARPKD in the general population. Although most patients are diagnosed in utero or at birth, mild cases may not become apparent until adolescence or adulthood. ARPKD can affect individuals of any ethnic group. | Affects of Autosomal Recessive Polycystic Kidney Disease. ARPKD affects males and females in equal numbers. The incidence of ARPKD is estimated to occur in approximately 1 in 20,000 individuals in the general population. Approximately ~1/70 people carry a single mutation in the PKHD1 gene. Because some people may go undiagnosed, it is difficult to determine the true frequency of ARPKD in the general population. Although most patients are diagnosed in utero or at birth, mild cases may not become apparent until adolescence or adulthood. ARPKD can affect individuals of any ethnic group. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_4 | Related disorders of Autosomal Recessive Polycystic Kidney Disease | Symptoms of the following disorders can be similar to those of ARPKD. Comparisons may be useful for a differential diagnosis.Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. Since ADPKD is a dominant disease, in most affected individuals have a family history of PKD, unlike ARPKD. Symptoms caused by cyst formation in the kidneys include high blood pressure (hypertension), pain on the sides of the body between the last rib and the hip (flank pain), blood in the urine (hematuria) and progressively poor function of the kidneys (kidney insufficiency). In ~50 percent of patients, ADPKD progresses to end stage renal disease by 60 years of age, requiring renal replacement therapy, either dialysis or renal transplantation. ADPKD is not simply a kidney disorder and other organ systems of the body can potentially be affected (multisystem disorder) by the development of cysts and other disease. The specific symptoms present in each person depend upon the specific organ systems involved. The liver, pancreas, a membrane covering the spinal cord and brain (arachnoid membrane), and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles) may develop cysts. Abnormalities affecting the heart and blood vessels (cardiovascular system) may also occur in individuals with ADPKD. ADPKD usually does not cause renal insufficiency until the fourth or fifth decade and was once known as “adult” polycystic kidney disease. However, it can occur in children and infants. ADPKD is mainly caused by mutations of one of two genes that create certain proteins essential for the proper health of the kidneys and other parts of the body. Rarely, atypical mutation combinations to the ADPKD genes can result in a disease that is similar to ARPKD. (For more information on this disorder, choose “ADPKD” as your search term in the Rare Disease Database.)Recently, two diseases similar to ARPKD due to PKHD1 mutations have been described. Two mutations to the DZIP1L gene can result in enlarged hyperechogenic kidneys and decline in renal function with renal failure in the teens or twenties. Patients do not seem to develop hepatic fibrosis. DZIP1L encodes a cilia related protein. In the second disease, polycystic kidney disease with hyperinsulinemic hypoglycemia (HIPKD) is caused by two mutations to in the PMM2 gene including at least one specific promoter mutation. PMM2 encodes a key enzyme in N-glycosylation, and two PMM2 mutations usually result in the congenital disorder of glycosylation type 1a (CDG1A), a multisystem disorder with prominent neurologic involvement, but the promoter mutation results in problems specific to the kidneys and liver. Kidneys are enlarged, multicystic and can result in renal failure. Cysts can be present in the liver, and as the name suggests, they often have hyperinsulinemic hypoglycemia.A variety of other disorders may have cystic kidneys as a feature. These disorders may sometimes be referred to as syndromic forms of polycystic kidney. These disorders usually have additional neurological, digital, eye and/or other symptoms and physical findings that distinguish them from ARPKD. These disorders include Bardet-Biedl syndrome, Meckel syndrome, Joubert syndrome, Senior-Loken syndrome, nephronophthisis, and oral-facial-digital syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Autosomal Recessive Polycystic Kidney Disease. Symptoms of the following disorders can be similar to those of ARPKD. Comparisons may be useful for a differential diagnosis.Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys. Since ADPKD is a dominant disease, in most affected individuals have a family history of PKD, unlike ARPKD. Symptoms caused by cyst formation in the kidneys include high blood pressure (hypertension), pain on the sides of the body between the last rib and the hip (flank pain), blood in the urine (hematuria) and progressively poor function of the kidneys (kidney insufficiency). In ~50 percent of patients, ADPKD progresses to end stage renal disease by 60 years of age, requiring renal replacement therapy, either dialysis or renal transplantation. ADPKD is not simply a kidney disorder and other organ systems of the body can potentially be affected (multisystem disorder) by the development of cysts and other disease. The specific symptoms present in each person depend upon the specific organ systems involved. The liver, pancreas, a membrane covering the spinal cord and brain (arachnoid membrane), and the glands of the male reproductive tract that produce fluid that is part of semen (seminal vesicles) may develop cysts. Abnormalities affecting the heart and blood vessels (cardiovascular system) may also occur in individuals with ADPKD. ADPKD usually does not cause renal insufficiency until the fourth or fifth decade and was once known as “adult” polycystic kidney disease. However, it can occur in children and infants. ADPKD is mainly caused by mutations of one of two genes that create certain proteins essential for the proper health of the kidneys and other parts of the body. Rarely, atypical mutation combinations to the ADPKD genes can result in a disease that is similar to ARPKD. (For more information on this disorder, choose “ADPKD” as your search term in the Rare Disease Database.)Recently, two diseases similar to ARPKD due to PKHD1 mutations have been described. Two mutations to the DZIP1L gene can result in enlarged hyperechogenic kidneys and decline in renal function with renal failure in the teens or twenties. Patients do not seem to develop hepatic fibrosis. DZIP1L encodes a cilia related protein. In the second disease, polycystic kidney disease with hyperinsulinemic hypoglycemia (HIPKD) is caused by two mutations to in the PMM2 gene including at least one specific promoter mutation. PMM2 encodes a key enzyme in N-glycosylation, and two PMM2 mutations usually result in the congenital disorder of glycosylation type 1a (CDG1A), a multisystem disorder with prominent neurologic involvement, but the promoter mutation results in problems specific to the kidneys and liver. Kidneys are enlarged, multicystic and can result in renal failure. Cysts can be present in the liver, and as the name suggests, they often have hyperinsulinemic hypoglycemia.A variety of other disorders may have cystic kidneys as a feature. These disorders may sometimes be referred to as syndromic forms of polycystic kidney. These disorders usually have additional neurological, digital, eye and/or other symptoms and physical findings that distinguish them from ARPKD. These disorders include Bardet-Biedl syndrome, Meckel syndrome, Joubert syndrome, Senior-Loken syndrome, nephronophthisis, and oral-facial-digital syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_5 | Diagnosis of Autosomal Recessive Polycystic Kidney Disease | ARPKD may be suspected before birth based upon clinical findings (e.g., palpable flank mass, underdeveloped lungs, oligohydramnios, and hypertension). Radiologic imaging including sonograms, ultrasound and magnetic resonance imaging (MRI) can be used to aid in obtaining a diagnosis of ARPKD. In addition to detecting kidney abnormalities, various radiologic imaging techniques can also be used to identify non-obstructive widening (dilatation) of the intraheptic ducts within the liver.A prenatal ultrasound may reveal enlarged kidneys (as early 18 weeks after conception in some cases). An ultrasound may also reveal innumerable small cysts that are actually dilated collecting tubules. True renal cysts may also be present. An ultrasound, however, may fail to detect kidney enlargement or oligohydramnios.Genetic testing for mutations in the PKHD1 genes is available at several different laboratories (see Genetic Testing Registry: https://www.ncbi.nlm.nih.gov/gtr/). Genetic testing may be employed for prenatal or preimplantation genetic diagnostics for some at-risk families who have had at least one pregnancy diagnosed with ARPKD. Given the overlap in symptoms between ARPKD and the diseases listed above, analysis by a next generation sequencing panel of PKD or nephrology genes, or whole exome sequencing, is recommended for diagnostics. | Diagnosis of Autosomal Recessive Polycystic Kidney Disease. ARPKD may be suspected before birth based upon clinical findings (e.g., palpable flank mass, underdeveloped lungs, oligohydramnios, and hypertension). Radiologic imaging including sonograms, ultrasound and magnetic resonance imaging (MRI) can be used to aid in obtaining a diagnosis of ARPKD. In addition to detecting kidney abnormalities, various radiologic imaging techniques can also be used to identify non-obstructive widening (dilatation) of the intraheptic ducts within the liver.A prenatal ultrasound may reveal enlarged kidneys (as early 18 weeks after conception in some cases). An ultrasound may also reveal innumerable small cysts that are actually dilated collecting tubules. True renal cysts may also be present. An ultrasound, however, may fail to detect kidney enlargement or oligohydramnios.Genetic testing for mutations in the PKHD1 genes is available at several different laboratories (see Genetic Testing Registry: https://www.ncbi.nlm.nih.gov/gtr/). Genetic testing may be employed for prenatal or preimplantation genetic diagnostics for some at-risk families who have had at least one pregnancy diagnosed with ARPKD. Given the overlap in symptoms between ARPKD and the diseases listed above, analysis by a next generation sequencing panel of PKD or nephrology genes, or whole exome sequencing, is recommended for diagnostics. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_135_6 | Therapies of Autosomal Recessive Polycystic Kidney Disease | TreatmentThe treatment of ARPKD is directed toward the specific symptoms that are apparent in each individual. Specific treatments are aimed at preserving kidney and liver function. In infancy many children with respiratory difficulties may require mechanical ventilation to assist breathing. Medications such as nitric oxide can help provide oxygen to (oxygenate) the lungs.In severe cases, newborns that experience decreased urine production (oliguria) or no passage of urine (anuria) may require peritoneal dialysis during the first few days of life.Medications can be used to control and manage high blood pressure, specifically angiotensin-converting enzyme (ACE) inhibitors. In some individuals, high blood pressure can be resistant to therapy (refractory) and severe enough to require more than one medication. Antibiotics may be used to treat urinary tract infections or cholangitis.Some children may require nutritional supplements including vitamin D, iron, bicarbonate and citrate. Adequate fluid and salt supplementation may also be necessary. Because of feeding difficulties and growth delays, some children may require the insertion of a tube through a small surgical opening in the stomach (gastrostomy) or a tube through the nose, down the esophagus and into the stomach (nasogastric tube). These tubes are used to directly provide essential nutrients. In severe cases, growth hormone therapy may be necessary.Individuals with end-stage renal disease, in which the kidneys no longer function, require dialysis or kidney transplant. Dialysis is a procedure in which a machine is used to perform some of the functions of the kidney – filtering waste products from the bloodstream, helping to control blood pressure and helping to maintain proper levels of essential chemicals such as potassium. End-stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant. The rate of progression of kidney dysfunction to end-stage renal disease can vary greatly from one person to another. Some individuals require a kidney transplant in childhood; others may not require a transplant until adulthood, or not at all.Progressive portal hypertension may require treatment with a portacaval shunt, in which a connection is made between the portal vein and the inferior vena cava, the main vein that drains blood from the lower two-thirds of the body. A portacaval shunt is designed to relieve high blood pressure of the portal vein.Variceal bleeding is a medical emergency and requires immediate treatment. Variceal bleeding may be treated by sclerotherapy, a procedure in which a solution such as sodium chloride is injected into an affected blood vessel. The solution irritates the blood vessel eventually causing it to scar and the blood to clot. A small percentage of individuals with ARPKD may eventually require liver transplantation.Erythropoietin may be used to stimulate the bone marrow to produce red blood cells in some children with ARPKD who experience anemia. Surgical removal of the spleen (splenectomy) has been used in some cases to treat severe splenomegaly.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Autosomal Recessive Polycystic Kidney Disease. TreatmentThe treatment of ARPKD is directed toward the specific symptoms that are apparent in each individual. Specific treatments are aimed at preserving kidney and liver function. In infancy many children with respiratory difficulties may require mechanical ventilation to assist breathing. Medications such as nitric oxide can help provide oxygen to (oxygenate) the lungs.In severe cases, newborns that experience decreased urine production (oliguria) or no passage of urine (anuria) may require peritoneal dialysis during the first few days of life.Medications can be used to control and manage high blood pressure, specifically angiotensin-converting enzyme (ACE) inhibitors. In some individuals, high blood pressure can be resistant to therapy (refractory) and severe enough to require more than one medication. Antibiotics may be used to treat urinary tract infections or cholangitis.Some children may require nutritional supplements including vitamin D, iron, bicarbonate and citrate. Adequate fluid and salt supplementation may also be necessary. Because of feeding difficulties and growth delays, some children may require the insertion of a tube through a small surgical opening in the stomach (gastrostomy) or a tube through the nose, down the esophagus and into the stomach (nasogastric tube). These tubes are used to directly provide essential nutrients. In severe cases, growth hormone therapy may be necessary.Individuals with end-stage renal disease, in which the kidneys no longer function, require dialysis or kidney transplant. Dialysis is a procedure in which a machine is used to perform some of the functions of the kidney – filtering waste products from the bloodstream, helping to control blood pressure and helping to maintain proper levels of essential chemicals such as potassium. End-stage renal disease is not reversible so individuals will require lifelong dialysis treatment or a kidney transplant. The rate of progression of kidney dysfunction to end-stage renal disease can vary greatly from one person to another. Some individuals require a kidney transplant in childhood; others may not require a transplant until adulthood, or not at all.Progressive portal hypertension may require treatment with a portacaval shunt, in which a connection is made between the portal vein and the inferior vena cava, the main vein that drains blood from the lower two-thirds of the body. A portacaval shunt is designed to relieve high blood pressure of the portal vein.Variceal bleeding is a medical emergency and requires immediate treatment. Variceal bleeding may be treated by sclerotherapy, a procedure in which a solution such as sodium chloride is injected into an affected blood vessel. The solution irritates the blood vessel eventually causing it to scar and the blood to clot. A small percentage of individuals with ARPKD may eventually require liver transplantation.Erythropoietin may be used to stimulate the bone marrow to produce red blood cells in some children with ARPKD who experience anemia. Surgical removal of the spleen (splenectomy) has been used in some cases to treat severe splenomegaly.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | 135 | Autosomal Recessive Polycystic Kidney Disease |
nord_136_0 | Overview of Axenfeld-Rieger Syndrome | SummaryAxenfeld-Rieger syndrome (ARS) is a rare genetic disorder that affects the eye as well as other parts of the body. It is estimated to occur in approximately 1 person in 50,000 worldwide. The disorder affects males and females equally and has been observed in patients from various ethnic backgrounds from all over the world. Signs and symptoms of ARS can be divided into ocular and non-ocular (systemic). Ocular features include, among others, an underdeveloped iris (iris hypoplasia), displacement of the pupil of the eye so that it is not centered (corectopia), full thickness tears in the iris of the eyes, an opaque ring around the outer edge of the cornea (posterior embryotoxon) and very rarely a small cornea (microcornea). Non-ocular features include, among others, dental and craniofacial abnormalities, hearing loss, excessive skin around the navel and very rarely a smaller than usual anal opening (refer to the ‘Signs & Symptoms’ section of this report for more information).ARS is the result of abnormal embryonic development, so the condition is usually diagnosed during infancy or childhood. A serious consequence of ARS is glaucoma, which usually develops later in childhood or adulthood. Glaucoma is often due to increased fluid pressure within the eyeball and can lead to complete permanent blindness if left untreated. Thus, the main course of treatment is the effective management of glaucoma, medically or surgically (if medications are not effective).IntroductionThe Axenfeld anomaly is defined as eye peripheral anterior segment defects and was first described in 1920 by the German ophthalmologist Theodor Axenfeld. Later in 1934, Rieger described the Rieger anomaly as central changes in the iris of the eye along with features mentioned in Axenfeld anomaly.Axenfeld syndrome and Rieger syndrome are defined as Axenfeld anomaly and Rieger anomaly accompanied by systemic effects, respectively. Distinction between these four conditions was difficult and clinically irrelevant due to the overlap of clinical features between them as well as the involvement of the same gene changes (mutations). Thus, they are now all grouped under the same condition referred to as Axenfeld-Rieger syndrome. | Overview of Axenfeld-Rieger Syndrome. SummaryAxenfeld-Rieger syndrome (ARS) is a rare genetic disorder that affects the eye as well as other parts of the body. It is estimated to occur in approximately 1 person in 50,000 worldwide. The disorder affects males and females equally and has been observed in patients from various ethnic backgrounds from all over the world. Signs and symptoms of ARS can be divided into ocular and non-ocular (systemic). Ocular features include, among others, an underdeveloped iris (iris hypoplasia), displacement of the pupil of the eye so that it is not centered (corectopia), full thickness tears in the iris of the eyes, an opaque ring around the outer edge of the cornea (posterior embryotoxon) and very rarely a small cornea (microcornea). Non-ocular features include, among others, dental and craniofacial abnormalities, hearing loss, excessive skin around the navel and very rarely a smaller than usual anal opening (refer to the ‘Signs & Symptoms’ section of this report for more information).ARS is the result of abnormal embryonic development, so the condition is usually diagnosed during infancy or childhood. A serious consequence of ARS is glaucoma, which usually develops later in childhood or adulthood. Glaucoma is often due to increased fluid pressure within the eyeball and can lead to complete permanent blindness if left untreated. Thus, the main course of treatment is the effective management of glaucoma, medically or surgically (if medications are not effective).IntroductionThe Axenfeld anomaly is defined as eye peripheral anterior segment defects and was first described in 1920 by the German ophthalmologist Theodor Axenfeld. Later in 1934, Rieger described the Rieger anomaly as central changes in the iris of the eye along with features mentioned in Axenfeld anomaly.Axenfeld syndrome and Rieger syndrome are defined as Axenfeld anomaly and Rieger anomaly accompanied by systemic effects, respectively. Distinction between these four conditions was difficult and clinically irrelevant due to the overlap of clinical features between them as well as the involvement of the same gene changes (mutations). Thus, they are now all grouped under the same condition referred to as Axenfeld-Rieger syndrome. | 136 | Axenfeld-Rieger Syndrome |
nord_136_1 | Symptoms of Axenfeld-Rieger Syndrome | Ocular signs and symptomsOcular features of ARS usually occur in both eyes. The main ocular signs include an underdeveloped iris (iris hypoplasia), displacement of the pupil of the eye so that it is not centered (corectopia), one or more full thickness tears in the iris of the eye and an opaque ring around the outer edge of the cornea (posterior embryotoxon). Other features include adhesions in the front of the eye, between the iris and the edge of the cornea.Glaucoma is a group of diseases in which the eye's optic nerve is damaged. This damage is often secondary to increased pressure within the eyeball. Glaucoma is seen in approximately 50% of patients with ARS and can lead to complete permanent blindness if not treated. Fluid in the eye normally drains out of the eye through the angle formed by the junction of the iris and the cornea. Defects in the formation of the angle of the eye and/or adhesions that block this drainage route that are associated with ARS can lead to glaucoma.Systemic signs and symptomsSystemic signs include dental abnormalities including a congenital condition in which fewer teeth than normal are present (hypodontia), a tooth or teeth that are smaller than normal (microdontia), six or more missing teeth (oligodontia), complete absence of teeth (anodontia) and/or cone-shaped teeth.Other characteristics include craniofacial abnormalities resulting in a prominent forehead, face that appears to be flattened, widely spaced eyes (hypertelorism), broad flat bridge of the nose, under-developed bones of the upper jaw, thin upper lip and/or a protruding lower lip.Some patients with ARS may also present with failure of the skin around the navel to decrease in size after birth (a condition that is sometimes mistaken for an umbilical hernia) and very rarely an unusually small anal opening (anal stenosis). Rarely, a patient may in fact present with umbilical hernia — a protrusion of intestine through a weakness in the abdominal wall around the navel.Other rare manifestations include a congenital abnormality in which the urethra in males opens from a different location than its usual one on the head of the penis (hypospadias), abnormalities of the pituitary gland — an important hormone-producing gland found in the brain, arachnoid cysts — fluid-filled balloons under one of the membranes covering the brain and spinal cord, growth delay, heart defects and hearing abnormalities. | Symptoms of Axenfeld-Rieger Syndrome. Ocular signs and symptomsOcular features of ARS usually occur in both eyes. The main ocular signs include an underdeveloped iris (iris hypoplasia), displacement of the pupil of the eye so that it is not centered (corectopia), one or more full thickness tears in the iris of the eye and an opaque ring around the outer edge of the cornea (posterior embryotoxon). Other features include adhesions in the front of the eye, between the iris and the edge of the cornea.Glaucoma is a group of diseases in which the eye's optic nerve is damaged. This damage is often secondary to increased pressure within the eyeball. Glaucoma is seen in approximately 50% of patients with ARS and can lead to complete permanent blindness if not treated. Fluid in the eye normally drains out of the eye through the angle formed by the junction of the iris and the cornea. Defects in the formation of the angle of the eye and/or adhesions that block this drainage route that are associated with ARS can lead to glaucoma.Systemic signs and symptomsSystemic signs include dental abnormalities including a congenital condition in which fewer teeth than normal are present (hypodontia), a tooth or teeth that are smaller than normal (microdontia), six or more missing teeth (oligodontia), complete absence of teeth (anodontia) and/or cone-shaped teeth.Other characteristics include craniofacial abnormalities resulting in a prominent forehead, face that appears to be flattened, widely spaced eyes (hypertelorism), broad flat bridge of the nose, under-developed bones of the upper jaw, thin upper lip and/or a protruding lower lip.Some patients with ARS may also present with failure of the skin around the navel to decrease in size after birth (a condition that is sometimes mistaken for an umbilical hernia) and very rarely an unusually small anal opening (anal stenosis). Rarely, a patient may in fact present with umbilical hernia — a protrusion of intestine through a weakness in the abdominal wall around the navel.Other rare manifestations include a congenital abnormality in which the urethra in males opens from a different location than its usual one on the head of the penis (hypospadias), abnormalities of the pituitary gland — an important hormone-producing gland found in the brain, arachnoid cysts — fluid-filled balloons under one of the membranes covering the brain and spinal cord, growth delay, heart defects and hearing abnormalities. | 136 | Axenfeld-Rieger Syndrome |
nord_136_2 | Causes of Axenfeld-Rieger Syndrome | ARS is caused by changes (mutations) in several different genes and follows an autosomal dominant pattern of inheritance.Dominant genetic disorders typically occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. The word ”autosomal” means that the genetic disorder is not associated with one of the sex chromosomes, but rather with the non-sex (or autosomal) chromosomes.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 4q25-q26” refers to a region between bands 25 and 26 on the long arm of chromosome 4. Chromosome 13q14 refers to a site at band 14 on the long arm of chromosome 13. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Several genetic studies have found two main genes associated with ARS: FOXC1 and PITX2. A wide spectrum of mutations in these genes contributes to the development of the disease. However, the genetic cause of ARS remains unclear in around 60% of patients.There are three types of ARS. ARS type I is associated with mutations in the PITX2 gene on chromosome 4 (4q25), whereas ARS type III is associated with mutations in the FOXC1 gene on chromosome 6 (6p25). ARS type II has been associated with chromosome 13 (13q14), but a specific gene is not yet identified. Typically, patients who present with associated systemic abnormalities tend to have a PITX2 mutation, whereas patients who only present with ocular features, sometimes alongside heart defects and hearing loss, tend to have a FOXC1 mutation. Other genetic changes are also rarely associated with ARS: deletion of the PAX6 gene on chromosome 11 (11p13) as well as deletion of the chromosome 16q23-q24 region.PTXI2 and FOXC1 are both genes that code for transcription factors that control other genes to regulate steps in embryonic development. The mechanism of ARS is not fully clear, but it is believed that the structural abnormalities seen in ARS originate from defects in the development and functions of cells that form the eye.ARS has also been reported to be associated with of gain of function mutations or extra copies of genes. This might increase the activity of proteins involved in the development of the eyes. | Causes of Axenfeld-Rieger Syndrome. ARS is caused by changes (mutations) in several different genes and follows an autosomal dominant pattern of inheritance.Dominant genetic disorders typically occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a changed (mutated) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. The word ”autosomal” means that the genetic disorder is not associated with one of the sex chromosomes, but rather with the non-sex (or autosomal) chromosomes.Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes.Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 4q25-q26” refers to a region between bands 25 and 26 on the long arm of chromosome 4. Chromosome 13q14 refers to a site at band 14 on the long arm of chromosome 13. The numbered bands specify the location of the thousands of genes that are present on each chromosome.Several genetic studies have found two main genes associated with ARS: FOXC1 and PITX2. A wide spectrum of mutations in these genes contributes to the development of the disease. However, the genetic cause of ARS remains unclear in around 60% of patients.There are three types of ARS. ARS type I is associated with mutations in the PITX2 gene on chromosome 4 (4q25), whereas ARS type III is associated with mutations in the FOXC1 gene on chromosome 6 (6p25). ARS type II has been associated with chromosome 13 (13q14), but a specific gene is not yet identified. Typically, patients who present with associated systemic abnormalities tend to have a PITX2 mutation, whereas patients who only present with ocular features, sometimes alongside heart defects and hearing loss, tend to have a FOXC1 mutation. Other genetic changes are also rarely associated with ARS: deletion of the PAX6 gene on chromosome 11 (11p13) as well as deletion of the chromosome 16q23-q24 region.PTXI2 and FOXC1 are both genes that code for transcription factors that control other genes to regulate steps in embryonic development. The mechanism of ARS is not fully clear, but it is believed that the structural abnormalities seen in ARS originate from defects in the development and functions of cells that form the eye.ARS has also been reported to be associated with of gain of function mutations or extra copies of genes. This might increase the activity of proteins involved in the development of the eyes. | 136 | Axenfeld-Rieger Syndrome |
nord_136_3 | Affects of Axenfeld-Rieger Syndrome | ARS is estimated to occur in about 1 in 1/50,000 newborns worldwide. It has been observed in patients from different ethnic origins including the Middle East as well as European, African, Asian, and South and North American populations. ARS seems to affect males and females in about equal numbers and is usually diagnosed in infants and children. Glaucoma, on the other hand, usually develops later in childhood or in adulthood. | Affects of Axenfeld-Rieger Syndrome. ARS is estimated to occur in about 1 in 1/50,000 newborns worldwide. It has been observed in patients from different ethnic origins including the Middle East as well as European, African, Asian, and South and North American populations. ARS seems to affect males and females in about equal numbers and is usually diagnosed in infants and children. Glaucoma, on the other hand, usually develops later in childhood or in adulthood. | 136 | Axenfeld-Rieger Syndrome |
nord_136_4 | Related disorders of Axenfeld-Rieger Syndrome | The following disorders may share genetic or structural similarities with ARS.Iridocorneal endothelial (ICE) syndrome is a spectrum of disorders that are acquired through age and are characterized by excessive fluid accumulation in the cornea (corneal edema), various abnormalities in the iris that progress over time, as well as an increased pressure inside the eyeball. ICE syndrome resembles ARS in many ways but can easily be distinguished from it. This disorder tends to affect females more than males and usually develops in adulthood. Signs of ICE syndrome tend to occur unilaterally (in only one eye) and often are not accompanied by systemic abnormalities. Aniridia (iris hypoplasia) is a condition in which the iris of the eye is underdeveloped (almost always bilaterally). It is often inherited in an autosomal dominant pattern and has some involvement of the PAX6 gene discussed above for ARS. Several structural features can differentiate it from ARS. (For more information on this disorder, choose “Aniridia” as your search term in the Rare Disease Database.)Peters plus syndrome is a condition in which the cornea of the eye is centrally opacified alongside other ocular changes. Peters plus syndrome affects the eyes and other parts of the body. When it only affects the eyes, it is referred to as Peters congenital glaucoma (or Peters anomaly). However, when Peters anomaly is associated with dwarfism, intellectual disability and abnormalities of the ear and cleft palate, it is known as Peters plus syndrome. Cataracts may also be present as well as other systemic features such as mild facial distortion and/or heart defects. Peters plus syndrome is inherited in an autosomal recessive pattern. It is differentiated from ARS mainly through the ocular changes. | Related disorders of Axenfeld-Rieger Syndrome. The following disorders may share genetic or structural similarities with ARS.Iridocorneal endothelial (ICE) syndrome is a spectrum of disorders that are acquired through age and are characterized by excessive fluid accumulation in the cornea (corneal edema), various abnormalities in the iris that progress over time, as well as an increased pressure inside the eyeball. ICE syndrome resembles ARS in many ways but can easily be distinguished from it. This disorder tends to affect females more than males and usually develops in adulthood. Signs of ICE syndrome tend to occur unilaterally (in only one eye) and often are not accompanied by systemic abnormalities. Aniridia (iris hypoplasia) is a condition in which the iris of the eye is underdeveloped (almost always bilaterally). It is often inherited in an autosomal dominant pattern and has some involvement of the PAX6 gene discussed above for ARS. Several structural features can differentiate it from ARS. (For more information on this disorder, choose “Aniridia” as your search term in the Rare Disease Database.)Peters plus syndrome is a condition in which the cornea of the eye is centrally opacified alongside other ocular changes. Peters plus syndrome affects the eyes and other parts of the body. When it only affects the eyes, it is referred to as Peters congenital glaucoma (or Peters anomaly). However, when Peters anomaly is associated with dwarfism, intellectual disability and abnormalities of the ear and cleft palate, it is known as Peters plus syndrome. Cataracts may also be present as well as other systemic features such as mild facial distortion and/or heart defects. Peters plus syndrome is inherited in an autosomal recessive pattern. It is differentiated from ARS mainly through the ocular changes. | 136 | Axenfeld-Rieger Syndrome |
nord_136_5 | Diagnosis of Axenfeld-Rieger Syndrome | ARS is commonly recognized by the presence of characteristic ocular features that may include non-ocular abnormalities. Depending on the clinical situation, genetic testing can help confirm a suspected diagnosis of ARS.Clinical testing and work-upThe work-up includes an initial examination of the eye to detect ocular abnormalities associated with the disease. Regular eye examinations are also done to monitor possible development of glaucoma. A physical examination for non-ocular features associated with ARS is also done. | Diagnosis of Axenfeld-Rieger Syndrome. ARS is commonly recognized by the presence of characteristic ocular features that may include non-ocular abnormalities. Depending on the clinical situation, genetic testing can help confirm a suspected diagnosis of ARS.Clinical testing and work-upThe work-up includes an initial examination of the eye to detect ocular abnormalities associated with the disease. Regular eye examinations are also done to monitor possible development of glaucoma. A physical examination for non-ocular features associated with ARS is also done. | 136 | Axenfeld-Rieger Syndrome |
nord_136_6 | Therapies of Axenfeld-Rieger Syndrome | TreatmentThe main course of treatment in ARS is the management of glaucoma (if present) with medications, usually consisting of eye drops. These medications are mainly used to lower the pressure inside the eyeball (intra-ocular pressure). If eyedrops are not sufficient to control the glaucoma, surgery could be considered.For the non-ocular features of ARS, effective coordination of care with other healthcare professionals is important for complete evaluation and treatment. With age, certain patients with an uncentered pupil (corectopia) or multiple full thickness holes in the eye may experience an increased intolerance for light (photophobia). For these patients, special eye lenses may be beneficial.Genetic counseling may also be helpful for patients and their families. | Therapies of Axenfeld-Rieger Syndrome. TreatmentThe main course of treatment in ARS is the management of glaucoma (if present) with medications, usually consisting of eye drops. These medications are mainly used to lower the pressure inside the eyeball (intra-ocular pressure). If eyedrops are not sufficient to control the glaucoma, surgery could be considered.For the non-ocular features of ARS, effective coordination of care with other healthcare professionals is important for complete evaluation and treatment. With age, certain patients with an uncentered pupil (corectopia) or multiple full thickness holes in the eye may experience an increased intolerance for light (photophobia). For these patients, special eye lenses may be beneficial.Genetic counseling may also be helpful for patients and their families. | 136 | Axenfeld-Rieger Syndrome |
nord_137_0 | Overview of Babesiosis | Babesiosis is a rare infectious disease caused by single-celled microorganisms (protozoa) belonging to the Babesia family. It is believed that the Babesia protozoa are usually carried and transmitted by ticks (vectors). Babesiosis occurs primarily in animals; however, in rare cases, babesiosis infection may occur in humans. Certain Babesia species are known to cause babesiosis infection in humans (e.g., Babesia microti), and the deer tick is a known vector. Human babesiosis infection may cause fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia). Symptoms may be mild in otherwise healthy people; in addition, some infected individuals may exhibit no symptoms (asymptomatic). However, a severe form of babesiosis, which may be life-threatening if untreated, may occur in individuals who have had their spleens removed (splenectomized) or who have an impaired immune system. A different form of babesiosis has been reported in Europe that is associated with a more severe expression of symptoms. | Overview of Babesiosis. Babesiosis is a rare infectious disease caused by single-celled microorganisms (protozoa) belonging to the Babesia family. It is believed that the Babesia protozoa are usually carried and transmitted by ticks (vectors). Babesiosis occurs primarily in animals; however, in rare cases, babesiosis infection may occur in humans. Certain Babesia species are known to cause babesiosis infection in humans (e.g., Babesia microti), and the deer tick is a known vector. Human babesiosis infection may cause fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia). Symptoms may be mild in otherwise healthy people; in addition, some infected individuals may exhibit no symptoms (asymptomatic). However, a severe form of babesiosis, which may be life-threatening if untreated, may occur in individuals who have had their spleens removed (splenectomized) or who have an impaired immune system. A different form of babesiosis has been reported in Europe that is associated with a more severe expression of symptoms. | 137 | Babesiosis |
nord_137_1 | Symptoms of Babesiosis | Most people with babesiosis do not experience any symptoms (asymptomatic) or experience only mild symptoms. However, in some cases, babesiosis can cause severe complications. These severe cases usually only occur in individuals greater than 50 years of age, individuals who have impaired immune systems (immunocompromised), or individuals who have had their spleen removed (splenectomized).The symptoms associated with babesiosis usually develop approximately one to four weeks (incubation period) after exposure to the parasite. Symptoms vary greatly from case to case. The initial symptoms may include fever, a general feeling of ill health (malaise), fatigue, and loss of appetite. Additional early symptoms include joint pain (arthralgia), muscle pain (myalgia), chills, sweats, and headaches.Affected individuals may also have additional symptoms including nausea, vomiting, and/or abdominal pain. In some cases, an abnormally large liver and or spleen (hepatosplenomegaly) may be present. Immune compromised individuals with severe babesiosis may have impaired kidney function and an abnormal yellow discoloration to their skin, mucous membranes, and whites of the eyes (jaundice).Laboratory examination of blood samples from affected individuals may reveal abnormally low levels of red blood cells (hemolytic anemia) due to their destruction by the parasite. Additional laboratory findings may include abnormally low levels of platelets (thrombocytopenia) and white blood cells (leukopenia).In 20-25 percent of human babesiosis cases, affected individuals also have Lyme disease. Individuals who have simultaneous infection with both diseases usually experience more severe expression of symptoms and a longer duration of those symptoms. Individuals with babesiosis may also have another infectious disease known as ehrlichiosis. In rare cases, an individual can be simultaneously affected by all three diseases.In rare cases, this infection may be responsible for a respiratory condition known as adult respiratory distress syndrome (ARDS). (For more information on this disorder, choose “Adult Respiratory Distress” as your search term in the Rare Disease Database.) | Symptoms of Babesiosis. Most people with babesiosis do not experience any symptoms (asymptomatic) or experience only mild symptoms. However, in some cases, babesiosis can cause severe complications. These severe cases usually only occur in individuals greater than 50 years of age, individuals who have impaired immune systems (immunocompromised), or individuals who have had their spleen removed (splenectomized).The symptoms associated with babesiosis usually develop approximately one to four weeks (incubation period) after exposure to the parasite. Symptoms vary greatly from case to case. The initial symptoms may include fever, a general feeling of ill health (malaise), fatigue, and loss of appetite. Additional early symptoms include joint pain (arthralgia), muscle pain (myalgia), chills, sweats, and headaches.Affected individuals may also have additional symptoms including nausea, vomiting, and/or abdominal pain. In some cases, an abnormally large liver and or spleen (hepatosplenomegaly) may be present. Immune compromised individuals with severe babesiosis may have impaired kidney function and an abnormal yellow discoloration to their skin, mucous membranes, and whites of the eyes (jaundice).Laboratory examination of blood samples from affected individuals may reveal abnormally low levels of red blood cells (hemolytic anemia) due to their destruction by the parasite. Additional laboratory findings may include abnormally low levels of platelets (thrombocytopenia) and white blood cells (leukopenia).In 20-25 percent of human babesiosis cases, affected individuals also have Lyme disease. Individuals who have simultaneous infection with both diseases usually experience more severe expression of symptoms and a longer duration of those symptoms. Individuals with babesiosis may also have another infectious disease known as ehrlichiosis. In rare cases, an individual can be simultaneously affected by all three diseases.In rare cases, this infection may be responsible for a respiratory condition known as adult respiratory distress syndrome (ARDS). (For more information on this disorder, choose “Adult Respiratory Distress” as your search term in the Rare Disease Database.) | 137 | Babesiosis |
nord_137_2 | Causes of Babesiosis | Babesiosis is caused by single-celled microorganisms (protozoa) from the genus Babesia. These microorganisms are parasites that invade red blood cells (erythrocytes).There are more than 100 species of Babesia. In most cases, the two species of Babesia that cause disease in humans (pathogenic) are Babesia microti and Babesia divergens. The species involved varies depending upon specific geographic location.The major cause of babesiosis in the northeastern United States is infection by B. microti. In California and Washington a new Babesia parasite, called WA-1, is believed to be responsible for the disorder. In Europe, B. divergens and B. bovis are usually responsible for babesiosis.Babesia protozoa such as B. microti are transmitted to humans through the bite of infected ticks. The ticks serve as “vectors,” the term for any organism that is infected with and later transmits a particular disease agent (e.g., bacterium or virus) to another organism, which may then become infected. The deer tick (Ixodes dammini or scapularis) is the most common vector that transmits babesiosis.In extremely rare cases, babesiosis may be transmitted following a blood transfusion with blood that is contaminated with the microorganism. | Causes of Babesiosis. Babesiosis is caused by single-celled microorganisms (protozoa) from the genus Babesia. These microorganisms are parasites that invade red blood cells (erythrocytes).There are more than 100 species of Babesia. In most cases, the two species of Babesia that cause disease in humans (pathogenic) are Babesia microti and Babesia divergens. The species involved varies depending upon specific geographic location.The major cause of babesiosis in the northeastern United States is infection by B. microti. In California and Washington a new Babesia parasite, called WA-1, is believed to be responsible for the disorder. In Europe, B. divergens and B. bovis are usually responsible for babesiosis.Babesia protozoa such as B. microti are transmitted to humans through the bite of infected ticks. The ticks serve as “vectors,” the term for any organism that is infected with and later transmits a particular disease agent (e.g., bacterium or virus) to another organism, which may then become infected. The deer tick (Ixodes dammini or scapularis) is the most common vector that transmits babesiosis.In extremely rare cases, babesiosis may be transmitted following a blood transfusion with blood that is contaminated with the microorganism. | 137 | Babesiosis |
nord_137_3 | Affects of Babesiosis | Babesiosis is a rare infectious disease that affects males and females in equal numbers. It can affect individuals of any age although it is more likely to occur in people over 50 years of age, people who have weakened immune systems, and people who have had their spleens removed.In the United States, most cases are confined to the northeastern coast in the states of New York, Massachusetts, and Connecticut. The infected tick is present in greater numbers in these areas (endemic). Islands off the northeastern coast including Long Island, Martha's Vineyard, Nantucket, and Block Island are also areas where the tick may be found. Cases of babesiosis have also been reported in Washington, California, Georgia, New Jersey and Wisconsin. A more serious form of babesiosis occurs in Europe.Approximately 200 cases of babesiosis were reported in the United States during the 1980s. More than 450 cases have been reported in the medical literature. However, because some affected individuals may develop few associated symptoms and findings, the disorder may often remain unrecognized and may therefore be underdiagnosed, making it difficult to determine the true frequency of babesiosis in the general population. The disease has been diagnosed with greater frequency during the 1990s. | Affects of Babesiosis. Babesiosis is a rare infectious disease that affects males and females in equal numbers. It can affect individuals of any age although it is more likely to occur in people over 50 years of age, people who have weakened immune systems, and people who have had their spleens removed.In the United States, most cases are confined to the northeastern coast in the states of New York, Massachusetts, and Connecticut. The infected tick is present in greater numbers in these areas (endemic). Islands off the northeastern coast including Long Island, Martha's Vineyard, Nantucket, and Block Island are also areas where the tick may be found. Cases of babesiosis have also been reported in Washington, California, Georgia, New Jersey and Wisconsin. A more serious form of babesiosis occurs in Europe.Approximately 200 cases of babesiosis were reported in the United States during the 1980s. More than 450 cases have been reported in the medical literature. However, because some affected individuals may develop few associated symptoms and findings, the disorder may often remain unrecognized and may therefore be underdiagnosed, making it difficult to determine the true frequency of babesiosis in the general population. The disease has been diagnosed with greater frequency during the 1990s. | 137 | Babesiosis |
nord_137_4 | Related disorders of Babesiosis | Symptoms of the following disorders can be similar to those of babesiosis. Comparisons may be useful for a differential diagnosis:Malaria is an infectious disease that is caused by single-celled microorganisms (protozoa) of the Plasmodium genus and spread by the bite of an infected mosquito (Anopheles). Major symptoms may include fever, chills, listlessness, loss of appetite, headaches, muscle aches, and other flu-like symptoms. Additional symptoms may include muscle spasms and rigidity, profuse sweating, cold sores, abnormally fast heartbeat, and difficulty breathing. The severity of the symptoms varies greatly from case to case. Low levels of circulating red blood cells (anemia), weight loss, and a mild yellowish discoloration of the skin, mucous membranes, and whites of the eyes (jaundice) may also occur. Four different species of the Plasmodium genus may cause malaria. (For more information on this disorder, choose “Malaria” as your search term in the Rare Disease Database.)Lyme disease is an infectious disease caused by the spirochete bacterium Borrelia burgdorferi. The bacterium is carried and transmitted by deer ticks (Ixodes dammini). In most cases, Lyme disease is first characterized by the appearance of a red skin lesion (erythema chronicum migrans), which begins as a small elevated round spot (papule) that expands to at least five centimeters in diameter. Symptoms may then progress to include low-grade fever, chills, muscle aches (myalgia), headache, a general feeling of weakness and fatigue (malaise), and/or pain and stiffness of the large joints (infectious arthritis), especially in the knees. Such symptoms may tend to occur in recurrent cycles. In severe cases, heart muscle (myocardial) and/or neurological abnormalities may occur. Most cases of Lyme disease occur in the northeastern United States. However, cases have occurred in other areas of the United States as well as other countries including China, Japan, Australia, and several countries in Europe. (For more information on this disease, choose “Lyme” as your search term in the Rare Disease Database.)Toxoplasmosis is an infectious disorder that is caused by a single-celled parasite known as Toxoplasma gondii that often infects cats. This infection is found worldwide and may be acquired or transmitted to a fetus from an infected mother. Individuals may also develop toxoplasmosis by eating partially cooked meat especially pork. Accidental swallowing of Toxoplasma eggs also results in development of toxoplasmosis. This may occur by touching one's mouth after gardening near dirt infected with the eggs or cleaning the litter of an infected cat. Symptoms may include fatigue, rash, high fever, chills, and inflammation of the liver (hepatitis). Lesions may also occur in the lungs, heart, skin, muscle, and/or brain. (For more information on this disorder, choose “Toxoplasmosis” as your search term in the Rare Disease Database.)Human monocytic ehrlichiosis (HME), a rare infectious disease, is caused by a bacterium from the “Ehrlichia” family known as Ehrlichia chaffeensis. The invading bacteria spread through blood and lymphatic vessels and invade certain cells that play an essential role in the body's immune system (monocytes and macrophages). In individuals with HME, the onset of symptoms usually occurs about three weeks after an individual has been bitten by a tick carrying the E. chaffeensis bacterium. Symptoms may initially include fever, chills, headaches, muscle pain (myalgia), and a general feeling of weakness and fatigue (malaise). Symptoms may then progress to include nausea, vomiting, loss of appetite (anorexia), and/or weight loss. Some affected individuals may also experience coughing, diarrhea, sore throat (pharyngitis), pain in the abdominal area, and/or confusion. Most cases have occurred in the mid-Atlantic and southeastern states in the United States. (For more information on this disease, choose “Human Monocytic Ehrlichiosis” as your search term in the Rare Disease Database.)Human granulocytic ehrlichiosis (HGE), a rare infectious disease, is caused by a bacterium from the “Ehrlichia” family that has not yet been named. The bacterium, which is carried and transmitted by ticks (vectors), invades certain granular white blood cells (neutrophils) that play a role in engulfing bacteria, removing them from the blood, and destroying them (phagocytosis). In individuals with HGE, the onset of symptoms usually occurs approximately one week after an individual has been bitten by a tick carrying the Ehrlichia bacterium. In almost all cases, symptoms include fever, chills, muscle pain (myalgia), a general feeling of weakness and fatigue (malaise), and/or headaches. Some affected individuals may also experience coughing, nausea, vomiting, and/or confusion. Most cases have affected individuals in the Northeastern and Midwestern United States. (For more information on this disorder, choose “Human Granulocytic Ehrlichiosis” as your search term in the Rare Disease Database.) | Related disorders of Babesiosis. Symptoms of the following disorders can be similar to those of babesiosis. Comparisons may be useful for a differential diagnosis:Malaria is an infectious disease that is caused by single-celled microorganisms (protozoa) of the Plasmodium genus and spread by the bite of an infected mosquito (Anopheles). Major symptoms may include fever, chills, listlessness, loss of appetite, headaches, muscle aches, and other flu-like symptoms. Additional symptoms may include muscle spasms and rigidity, profuse sweating, cold sores, abnormally fast heartbeat, and difficulty breathing. The severity of the symptoms varies greatly from case to case. Low levels of circulating red blood cells (anemia), weight loss, and a mild yellowish discoloration of the skin, mucous membranes, and whites of the eyes (jaundice) may also occur. Four different species of the Plasmodium genus may cause malaria. (For more information on this disorder, choose “Malaria” as your search term in the Rare Disease Database.)Lyme disease is an infectious disease caused by the spirochete bacterium Borrelia burgdorferi. The bacterium is carried and transmitted by deer ticks (Ixodes dammini). In most cases, Lyme disease is first characterized by the appearance of a red skin lesion (erythema chronicum migrans), which begins as a small elevated round spot (papule) that expands to at least five centimeters in diameter. Symptoms may then progress to include low-grade fever, chills, muscle aches (myalgia), headache, a general feeling of weakness and fatigue (malaise), and/or pain and stiffness of the large joints (infectious arthritis), especially in the knees. Such symptoms may tend to occur in recurrent cycles. In severe cases, heart muscle (myocardial) and/or neurological abnormalities may occur. Most cases of Lyme disease occur in the northeastern United States. However, cases have occurred in other areas of the United States as well as other countries including China, Japan, Australia, and several countries in Europe. (For more information on this disease, choose “Lyme” as your search term in the Rare Disease Database.)Toxoplasmosis is an infectious disorder that is caused by a single-celled parasite known as Toxoplasma gondii that often infects cats. This infection is found worldwide and may be acquired or transmitted to a fetus from an infected mother. Individuals may also develop toxoplasmosis by eating partially cooked meat especially pork. Accidental swallowing of Toxoplasma eggs also results in development of toxoplasmosis. This may occur by touching one's mouth after gardening near dirt infected with the eggs or cleaning the litter of an infected cat. Symptoms may include fatigue, rash, high fever, chills, and inflammation of the liver (hepatitis). Lesions may also occur in the lungs, heart, skin, muscle, and/or brain. (For more information on this disorder, choose “Toxoplasmosis” as your search term in the Rare Disease Database.)Human monocytic ehrlichiosis (HME), a rare infectious disease, is caused by a bacterium from the “Ehrlichia” family known as Ehrlichia chaffeensis. The invading bacteria spread through blood and lymphatic vessels and invade certain cells that play an essential role in the body's immune system (monocytes and macrophages). In individuals with HME, the onset of symptoms usually occurs about three weeks after an individual has been bitten by a tick carrying the E. chaffeensis bacterium. Symptoms may initially include fever, chills, headaches, muscle pain (myalgia), and a general feeling of weakness and fatigue (malaise). Symptoms may then progress to include nausea, vomiting, loss of appetite (anorexia), and/or weight loss. Some affected individuals may also experience coughing, diarrhea, sore throat (pharyngitis), pain in the abdominal area, and/or confusion. Most cases have occurred in the mid-Atlantic and southeastern states in the United States. (For more information on this disease, choose “Human Monocytic Ehrlichiosis” as your search term in the Rare Disease Database.)Human granulocytic ehrlichiosis (HGE), a rare infectious disease, is caused by a bacterium from the “Ehrlichia” family that has not yet been named. The bacterium, which is carried and transmitted by ticks (vectors), invades certain granular white blood cells (neutrophils) that play a role in engulfing bacteria, removing them from the blood, and destroying them (phagocytosis). In individuals with HGE, the onset of symptoms usually occurs approximately one week after an individual has been bitten by a tick carrying the Ehrlichia bacterium. In almost all cases, symptoms include fever, chills, muscle pain (myalgia), a general feeling of weakness and fatigue (malaise), and/or headaches. Some affected individuals may also experience coughing, nausea, vomiting, and/or confusion. Most cases have affected individuals in the Northeastern and Midwestern United States. (For more information on this disorder, choose “Human Granulocytic Ehrlichiosis” as your search term in the Rare Disease Database.) | 137 | Babesiosis |
nord_137_5 | Diagnosis of Babesiosis | The diagnosis of babesiosis is made based upon a thorough clinical evaluation, a detailed patient history (e.g., recent tick bite), characteristic findings, and specialized tests such as the examination of blood smears that screen for the parasite inside red blood cells (erythrocytes). The diagnosis may also be confirmed by antibody testing (indirect immunofluorescent assay). | Diagnosis of Babesiosis. The diagnosis of babesiosis is made based upon a thorough clinical evaluation, a detailed patient history (e.g., recent tick bite), characteristic findings, and specialized tests such as the examination of blood smears that screen for the parasite inside red blood cells (erythrocytes). The diagnosis may also be confirmed by antibody testing (indirect immunofluorescent assay). | 137 | Babesiosis |
nord_137_6 | Therapies of Babesiosis | TreatmentIn most healthy people, babesiosis usually resolves spontaneously and causes few or no symptoms. People with an impaired immune system may require treatment with drugs such as clindamycin, quinine, and/or other antiparasitic or antibiotic drugs. Clindamycin and quinine are the drugs most commonly used to treat individuals with severe symptoms of babesiosis.Treatment with two different drugs, atovaquone and azithromycin, has been used in cases where clindamycin and quinine were ineffective. Individuals who have had their spleens removed who have severe cases of babesiosis may be treated with blood transfusions.PreventionIndividuals who will be exposed to areas with high numbers of tick vectors for the Babesia parasites (e.g., fields, wooded or marsh areas, etc.) should consider taking certain steps to prevent infection. Such steps should include wearing long-sleeved shirts, long pants, and hats; wearing light-colored clothing to make ticks more visible; using appropriate tick repellents; and carefully checking clothing and skin (particularly the scalp and the back of the neck) after being in such locations. | Therapies of Babesiosis. TreatmentIn most healthy people, babesiosis usually resolves spontaneously and causes few or no symptoms. People with an impaired immune system may require treatment with drugs such as clindamycin, quinine, and/or other antiparasitic or antibiotic drugs. Clindamycin and quinine are the drugs most commonly used to treat individuals with severe symptoms of babesiosis.Treatment with two different drugs, atovaquone and azithromycin, has been used in cases where clindamycin and quinine were ineffective. Individuals who have had their spleens removed who have severe cases of babesiosis may be treated with blood transfusions.PreventionIndividuals who will be exposed to areas with high numbers of tick vectors for the Babesia parasites (e.g., fields, wooded or marsh areas, etc.) should consider taking certain steps to prevent infection. Such steps should include wearing long-sleeved shirts, long pants, and hats; wearing light-colored clothing to make ticks more visible; using appropriate tick repellents; and carefully checking clothing and skin (particularly the scalp and the back of the neck) after being in such locations. | 137 | Babesiosis |
nord_138_0 | Overview of Bachmann-Bupp Syndrome | Bachmann-Bupp syndrome (BABS) is a rare genetic disorder caused by gain-of-function changes (pathogenic variants or mutations) in the ODC1 gene. Affected individuals have a distinctive type of hair loss (alopecia), global developmental delay, low muscle tone (hypotonia), nonspecific abnormal physical characteristics (dysmorphic features) and behavioral abnormalities. There is no cure for the disorder, but research is underway to better understand and treat this disease. Current treatment is aimed at the specific symptoms present in each individual. | Overview of Bachmann-Bupp Syndrome. Bachmann-Bupp syndrome (BABS) is a rare genetic disorder caused by gain-of-function changes (pathogenic variants or mutations) in the ODC1 gene. Affected individuals have a distinctive type of hair loss (alopecia), global developmental delay, low muscle tone (hypotonia), nonspecific abnormal physical characteristics (dysmorphic features) and behavioral abnormalities. There is no cure for the disorder, but research is underway to better understand and treat this disease. Current treatment is aimed at the specific symptoms present in each individual. | 138 | Bachmann-Bupp Syndrome |
nord_138_1 | Symptoms of Bachmann-Bupp Syndrome | There are 9 patients reported in the medical literature with BABS. From their histories, pathogenic variants in the ODC1 gene are thought to be responsible for the following:Other findings reported have been quite variable. One patient has been reported with a history of seizures starting at 14 years of age. One individual has been reported with congenital sensorineural hearing loss in one ear. Two individuals with congenital heart disease – one with mild pulmonary stenosis and the other with self-resolved ventricular septal defect – have been reported. Two individuals with brittle nails and one with underdeveloped (hypoplastic) toenails have been reported. One individual with an inward turned eye (esotropia), eyes that appear to be misaligned (pseudostrabismus) and a vision abnormality related to an overly curved cornea (myopic astigmatism) has been reported.Due to the small number of identified cases, the young age of reported patients and recent discovery of the condition, there is much yet to learn about the natural history of the disease. | Symptoms of Bachmann-Bupp Syndrome. There are 9 patients reported in the medical literature with BABS. From their histories, pathogenic variants in the ODC1 gene are thought to be responsible for the following:Other findings reported have been quite variable. One patient has been reported with a history of seizures starting at 14 years of age. One individual has been reported with congenital sensorineural hearing loss in one ear. Two individuals with congenital heart disease – one with mild pulmonary stenosis and the other with self-resolved ventricular septal defect – have been reported. Two individuals with brittle nails and one with underdeveloped (hypoplastic) toenails have been reported. One individual with an inward turned eye (esotropia), eyes that appear to be misaligned (pseudostrabismus) and a vision abnormality related to an overly curved cornea (myopic astigmatism) has been reported.Due to the small number of identified cases, the young age of reported patients and recent discovery of the condition, there is much yet to learn about the natural history of the disease. | 138 | Bachmann-Bupp Syndrome |
nord_138_2 | Causes of Bachmann-Bupp Syndrome | BABS is caused by changes (pathogenic variants or mutations) in the ornithine decarboxylase (ODC1) gene that are located at one end of the gene, the C terminus. Genes provide instructions for creating proteins which play a critical role in many bodily functions. Pathogenic variants in the ODC1 gene that cause BABS result in an elevated level of ODC protein followed by an increased conversion of ornithine to putrescine and increased accumulation of putrescine in the cells. These are called gain-of-function pathogenic variants.The penetrance of pathogenic variants in the ODC1 gene is believed to be 100%, meaning that any person who has a pathogenic change in one copy of their ODC1 gene is expected to develop the associated signs and symptoms. It is unclear whether variations in different portions of the gene or variants resulting in loss-of-function of specific proteins may cause other symptoms.BABS is inherited in an autosomal dominant pattern. Genetic conditions inherited in a dominant pattern occur when an individual has a pathogenic variant in one of their copies of a particular gene. Thus far, all reported patients whose parents have undergone molecular genetic testing have BABS as the result of a de novo, or new pathogenic variant that was not inherited. Each child of an individual with BABS has a 50% chance of inheriting the ODC1 pathogenic variant. To date, no individuals with BABS have reproduced and many are not yet of reproductive age. | Causes of Bachmann-Bupp Syndrome. BABS is caused by changes (pathogenic variants or mutations) in the ornithine decarboxylase (ODC1) gene that are located at one end of the gene, the C terminus. Genes provide instructions for creating proteins which play a critical role in many bodily functions. Pathogenic variants in the ODC1 gene that cause BABS result in an elevated level of ODC protein followed by an increased conversion of ornithine to putrescine and increased accumulation of putrescine in the cells. These are called gain-of-function pathogenic variants.The penetrance of pathogenic variants in the ODC1 gene is believed to be 100%, meaning that any person who has a pathogenic change in one copy of their ODC1 gene is expected to develop the associated signs and symptoms. It is unclear whether variations in different portions of the gene or variants resulting in loss-of-function of specific proteins may cause other symptoms.BABS is inherited in an autosomal dominant pattern. Genetic conditions inherited in a dominant pattern occur when an individual has a pathogenic variant in one of their copies of a particular gene. Thus far, all reported patients whose parents have undergone molecular genetic testing have BABS as the result of a de novo, or new pathogenic variant that was not inherited. Each child of an individual with BABS has a 50% chance of inheriting the ODC1 pathogenic variant. To date, no individuals with BABS have reproduced and many are not yet of reproductive age. | 138 | Bachmann-Bupp Syndrome |
nord_138_3 | Affects of Bachmann-Bupp Syndrome | BABS is a rare disorder that was first reported in the medical literature in 2018. As of November 2022, fewer than 30 affected individuals have been identified with the disorder worldwide. Rare diseases often go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. | Affects of Bachmann-Bupp Syndrome. BABS is a rare disorder that was first reported in the medical literature in 2018. As of November 2022, fewer than 30 affected individuals have been identified with the disorder worldwide. Rare diseases often go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. | 138 | Bachmann-Bupp Syndrome |
nord_138_4 | Related disorders of Bachmann-Bupp Syndrome | Symptoms of the following disorders can be similar to those of BABS. Comparisons may be useful for a differential diagnosis.Snijders Blok-Campeau syndrome (SNIBCPS) is an autosomal dominant neurodevelopmental genetic disorder caused by pathogenic variants in the CHD3 gene. SNIBCPS is characterized by developmental delay, macrocephaly, ventriculomegaly, hypotonia and joint laxity.Woodhouse-Sakati syndrome (WDSKS) is an autosomal recessive genetic condition caused by pathogenic variants in the DCAF17 gene. WDSKS is characterized by alopecia totalis, dystonia, hypogonadism and diabetes mellitus.Alopecia-intellectual disability syndrome 4 (APMR4) is an autosomal recessive genetic condition cause by pathogenic variants in the LSS gene. APMR4 is characterized by congenital alopecia, developmental delay and epilepsy.Intellectual developmental disorder with macrocephaly, seizures and speech delay (IDDMSSD) is an autosomal dominant condition caused by pathogenic variants in the PAK1 gene. IDDMSSD is characterized by developmental delay, macrocephaly, seizures and ataxia. There is also absence of hair and skin abnormalities as seen in BABS.Cowden syndrome is an autosomal dominant genetic condition caused by pathogenic variants in the PTEN gene. Cowden syndrome is characterized by developmental delay, macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules and increased risk for breast, thyroid and endometrial cancers.Additional disorders that can be mistaken for BABS include ectodermal dysplasias, but these are not typically associated with developmental delay or hypotonia and alopecia is present at birth (congenital) in most ectodermal dysplasias. | Related disorders of Bachmann-Bupp Syndrome. Symptoms of the following disorders can be similar to those of BABS. Comparisons may be useful for a differential diagnosis.Snijders Blok-Campeau syndrome (SNIBCPS) is an autosomal dominant neurodevelopmental genetic disorder caused by pathogenic variants in the CHD3 gene. SNIBCPS is characterized by developmental delay, macrocephaly, ventriculomegaly, hypotonia and joint laxity.Woodhouse-Sakati syndrome (WDSKS) is an autosomal recessive genetic condition caused by pathogenic variants in the DCAF17 gene. WDSKS is characterized by alopecia totalis, dystonia, hypogonadism and diabetes mellitus.Alopecia-intellectual disability syndrome 4 (APMR4) is an autosomal recessive genetic condition cause by pathogenic variants in the LSS gene. APMR4 is characterized by congenital alopecia, developmental delay and epilepsy.Intellectual developmental disorder with macrocephaly, seizures and speech delay (IDDMSSD) is an autosomal dominant condition caused by pathogenic variants in the PAK1 gene. IDDMSSD is characterized by developmental delay, macrocephaly, seizures and ataxia. There is also absence of hair and skin abnormalities as seen in BABS.Cowden syndrome is an autosomal dominant genetic condition caused by pathogenic variants in the PTEN gene. Cowden syndrome is characterized by developmental delay, macrocephaly, facial trichilemmomas, acral keratoses, papillomatous papules and increased risk for breast, thyroid and endometrial cancers.Additional disorders that can be mistaken for BABS include ectodermal dysplasias, but these are not typically associated with developmental delay or hypotonia and alopecia is present at birth (congenital) in most ectodermal dysplasias. | 138 | Bachmann-Bupp Syndrome |
nord_138_5 | Diagnosis of Bachmann-Bupp Syndrome | A diagnosis of BABS is based upon identification of characteristic symptoms and molecular genetic testing that reveals a pathogenic variant in the ODC1 gene. Consensus clinical diagnostic criteria have not been established.Clinical Testing and WorkupOther tests may be performed to assess specific symptoms. For example, if seizure activity is seen or suspected based on body shaking or staring spells, physicians may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and help to detect seizures. Several patients with BABS have had changes noted on brain MRI, but not with a recurrent pattern of abnormalities. | Diagnosis of Bachmann-Bupp Syndrome. A diagnosis of BABS is based upon identification of characteristic symptoms and molecular genetic testing that reveals a pathogenic variant in the ODC1 gene. Consensus clinical diagnostic criteria have not been established.Clinical Testing and WorkupOther tests may be performed to assess specific symptoms. For example, if seizure activity is seen or suspected based on body shaking or staring spells, physicians may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and help to detect seizures. Several patients with BABS have had changes noted on brain MRI, but not with a recurrent pattern of abnormalities. | 138 | Bachmann-Bupp Syndrome |
nord_138_6 | Therapies of Bachmann-Bupp Syndrome | Treatment
Following initial diagnosis, there are a variety of recommended evaluations. Evaluation with a gastroenterology/nutrition/feeding therapy team helps to investigate aspiration risk, nutritional status and signs of constipation. Developmental assessment is important to determine if early intervention services are needed. Neuropsychiatric evaluation is done to screen for behavior concerns. Ophthalmologic and audiology referrals are done to evaluate for vision or hearing concerns. A referral to a dermatologist is indicated if follicular cysts are present. A referral to a cardiologist is indicated if a heart murmur is present. If there is a concern for seizures, a neurologic evaluation with consideration of EEG might be recommended.The treatment of BABS is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Primary care physicians, geneticists, neurologists and other healthcare professionals may need to systematically and comprehensively plan treatment.Genetic counseling is recommended for families who have a child with BABS.Psychosocial support for the entire family is essential as well.Individuals with BABS are recommended to receive the following surveillance at each visit:Additionally, annual behavioral assessments, ophthalmology and audiology evaluations and skin checks for follicular cysts are recommended.Affected children may benefit from occupational, physical and speech therapy. Additional medical, social and/or vocational services including specialized learning programs may be necessary. | Therapies of Bachmann-Bupp Syndrome. Treatment
Following initial diagnosis, there are a variety of recommended evaluations. Evaluation with a gastroenterology/nutrition/feeding therapy team helps to investigate aspiration risk, nutritional status and signs of constipation. Developmental assessment is important to determine if early intervention services are needed. Neuropsychiatric evaluation is done to screen for behavior concerns. Ophthalmologic and audiology referrals are done to evaluate for vision or hearing concerns. A referral to a dermatologist is indicated if follicular cysts are present. A referral to a cardiologist is indicated if a heart murmur is present. If there is a concern for seizures, a neurologic evaluation with consideration of EEG might be recommended.The treatment of BABS is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Primary care physicians, geneticists, neurologists and other healthcare professionals may need to systematically and comprehensively plan treatment.Genetic counseling is recommended for families who have a child with BABS.Psychosocial support for the entire family is essential as well.Individuals with BABS are recommended to receive the following surveillance at each visit:Additionally, annual behavioral assessments, ophthalmology and audiology evaluations and skin checks for follicular cysts are recommended.Affected children may benefit from occupational, physical and speech therapy. Additional medical, social and/or vocational services including specialized learning programs may be necessary. | 138 | Bachmann-Bupp Syndrome |
nord_139_0 | Overview of Balantidiasis | Balantidiasis is a rare intestinal infection caused by the bacterium, Balantidium coli, a single celled parasite (ciliate protozoan) that frequently infects pigs but on occasion (rarely) infects humans. Some infected people may have no symptoms or only mild diarrhea and abdominal discomfort but others may experience more severe symptoms reminiscent of an acute inflammation of the intestines. Symptoms of Balantidiasis may be similar to those of other infections that cause intestinal inflammation, for example, amoebic dysentery. | Overview of Balantidiasis. Balantidiasis is a rare intestinal infection caused by the bacterium, Balantidium coli, a single celled parasite (ciliate protozoan) that frequently infects pigs but on occasion (rarely) infects humans. Some infected people may have no symptoms or only mild diarrhea and abdominal discomfort but others may experience more severe symptoms reminiscent of an acute inflammation of the intestines. Symptoms of Balantidiasis may be similar to those of other infections that cause intestinal inflammation, for example, amoebic dysentery. | 139 | Balantidiasis |
nord_139_1 | Symptoms of Balantidiasis | Most people with Balantidiasis are asymptomatic or present mild symptoms. Some individuals may become acutely ill with abnormally high temperatures, nausea, vomiting, abdominal pain, and bloody diarrhea. Such conditions may result in the excessive loss of water from the body (dehydration) and extreme exhaustion (prostration), especially if B. coli attacks the intestinal lining causing inflammation and possibly “crater-like” areas of damage (ulceration). In very severe cases, the ulcers may be deep enough to puncture the intestinal wall (perforation) resulting in acute inflammation of the peritoneum, the membrane that lines the abdomen (peritonitis). Occasionally, the ulcer may diminish lung function. | Symptoms of Balantidiasis. Most people with Balantidiasis are asymptomatic or present mild symptoms. Some individuals may become acutely ill with abnormally high temperatures, nausea, vomiting, abdominal pain, and bloody diarrhea. Such conditions may result in the excessive loss of water from the body (dehydration) and extreme exhaustion (prostration), especially if B. coli attacks the intestinal lining causing inflammation and possibly “crater-like” areas of damage (ulceration). In very severe cases, the ulcers may be deep enough to puncture the intestinal wall (perforation) resulting in acute inflammation of the peritoneum, the membrane that lines the abdomen (peritonitis). Occasionally, the ulcer may diminish lung function. | 139 | Balantidiasis |
nord_139_2 | Causes of Balantidiasis | Balantidiasis is a rare infectious disease caused by the single celled (protozoan) parasite Balantidium coli. This parasite may be passed directly to humans by contact with pig feces or indirectly by drinking contaminated water. Poor nutrition, a compromised immune system, or other illnesses may make a person vulnerable to more severe symptoms of this disease. | Causes of Balantidiasis. Balantidiasis is a rare infectious disease caused by the single celled (protozoan) parasite Balantidium coli. This parasite may be passed directly to humans by contact with pig feces or indirectly by drinking contaminated water. Poor nutrition, a compromised immune system, or other illnesses may make a person vulnerable to more severe symptoms of this disease. | 139 | Balantidiasis |
nord_139_3 | Affects of Balantidiasis | Balantidiasis is a rare infection that affects males and females in equal numbers. It typically occurs in tropical regions such as Brazil, New Guinea, and southern Iran. | Affects of Balantidiasis. Balantidiasis is a rare infection that affects males and females in equal numbers. It typically occurs in tropical regions such as Brazil, New Guinea, and southern Iran. | 139 | Balantidiasis |
nord_139_4 | Related disorders of Balantidiasis | Symptoms of the following disorders can be similar to those of Balantidiasis. Comparisons may be useful for a differential diagnosis:Ulcerative Colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and the urgent need to have a bowel movement (tenesmus). Weight loss and a decrease in appetite are also associated with Ulcerative Colitis. (For more information on this disorder, choose “Ulcerative Colitis” as your search term in the Rare Disease Database.)Crohn's Disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. Symptoms of this disorder include nausea, vomiting, fever, night sweats, loss of appetite, a general feeling of weakness, waves of abdominal pain and discomfort, diarrhea and rectal bleeding. (For more information on this disorder, choose “Crohn's” as your search term in the Rare Disease Database.)Irritable Bowel Syndrome, also known as Spastic Colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with Irritable Bowel Syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose “Irritable Bowel Syndrome” as your search term in the Rare Disease Database.)Chronic Erosive Gastritis is an inflammatory disorder characterized by multiple lesions in the mucosal lining of the stomach. Symptoms of this disorder may include a burning or heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of Chronic Erosive Gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose “Chronic Erosive Gastritis” as your search term in the Rare Disease Database.)Other infectious diseases have symptoms that are similar to those of Balantidiasis including amoebic dysentery, shigella dysentery, Yersinia enterocolitica infection, amebiasis, chronic fungal bowel infections, intestinal tuberculosis, and pseudomembranous colitis that is caused by excessive use of antibiotics. Ischemic Colitis and certain cancers such as abdominal lymphoma may also cause symptoms that are similar to those of Balantidiasis. | Related disorders of Balantidiasis. Symptoms of the following disorders can be similar to those of Balantidiasis. Comparisons may be useful for a differential diagnosis:Ulcerative Colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and the urgent need to have a bowel movement (tenesmus). Weight loss and a decrease in appetite are also associated with Ulcerative Colitis. (For more information on this disorder, choose “Ulcerative Colitis” as your search term in the Rare Disease Database.)Crohn's Disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. Symptoms of this disorder include nausea, vomiting, fever, night sweats, loss of appetite, a general feeling of weakness, waves of abdominal pain and discomfort, diarrhea and rectal bleeding. (For more information on this disorder, choose “Crohn's” as your search term in the Rare Disease Database.)Irritable Bowel Syndrome, also known as Spastic Colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with Irritable Bowel Syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose “Irritable Bowel Syndrome” as your search term in the Rare Disease Database.)Chronic Erosive Gastritis is an inflammatory disorder characterized by multiple lesions in the mucosal lining of the stomach. Symptoms of this disorder may include a burning or heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of Chronic Erosive Gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose “Chronic Erosive Gastritis” as your search term in the Rare Disease Database.)Other infectious diseases have symptoms that are similar to those of Balantidiasis including amoebic dysentery, shigella dysentery, Yersinia enterocolitica infection, amebiasis, chronic fungal bowel infections, intestinal tuberculosis, and pseudomembranous colitis that is caused by excessive use of antibiotics. Ischemic Colitis and certain cancers such as abdominal lymphoma may also cause symptoms that are similar to those of Balantidiasis. | 139 | Balantidiasis |
nord_139_5 | Diagnosis of Balantidiasis | Diagnosis of Balantidiasis. | 139 | Balantidiasis |
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nord_139_6 | Therapies of Balantidiasis | Balantidiasis can be diagnosed by laboratory testing of the stool. Immature B. coli parasites (trophozoites) are usually recoverable from the stool. A more complex and more invasive diagnostic method involves scraping the ulcer and examining the tissue for trophozoites.The antibiotic drug most frequently used to treat Balantidiasis is tetracycline. When tetracycline cannot be given (i.e., allergy), replacement drug therapy may include the drugs iodoquinol or metronidazole. It is not necessary to isolate (quarantine) a person who has Balantidiasis. However, the feces of infected individuals must be disposed of so that they do not come into contact with drinking water or food supplies. | Therapies of Balantidiasis. Balantidiasis can be diagnosed by laboratory testing of the stool. Immature B. coli parasites (trophozoites) are usually recoverable from the stool. A more complex and more invasive diagnostic method involves scraping the ulcer and examining the tissue for trophozoites.The antibiotic drug most frequently used to treat Balantidiasis is tetracycline. When tetracycline cannot be given (i.e., allergy), replacement drug therapy may include the drugs iodoquinol or metronidazole. It is not necessary to isolate (quarantine) a person who has Balantidiasis. However, the feces of infected individuals must be disposed of so that they do not come into contact with drinking water or food supplies. | 139 | Balantidiasis |
nord_140_0 | Overview of Balo Disease | Balo Disease is a rare and progressive variant of multiple sclerosis. It usually first appears in adulthood, but childhood cases have also been reported. While multiple sclerosis typically is a disease that waxes and wanes, Balo Disease is different in that it tends to be rapidly progressive. Symptoms may include headache, seizures, gradual paralysis, involuntary muscle spasms, and cognitive loss. The alternative names for Balo Disease, concentric sclerosis or Balo concentric sclerosis, refer to the fact that Balo Disease is characterized by bands of intact myelin (the sheath of fatty substances surrounding nerve fibers), alternating with rings of loss of myelin (demyelination), in various parts of the brain and brain stem. The symptoms of Balo Disease vary, according to the areas of the brain that are affected. Symptoms may progress rapidly over several weeks or more slowly over two to three years. | Overview of Balo Disease. Balo Disease is a rare and progressive variant of multiple sclerosis. It usually first appears in adulthood, but childhood cases have also been reported. While multiple sclerosis typically is a disease that waxes and wanes, Balo Disease is different in that it tends to be rapidly progressive. Symptoms may include headache, seizures, gradual paralysis, involuntary muscle spasms, and cognitive loss. The alternative names for Balo Disease, concentric sclerosis or Balo concentric sclerosis, refer to the fact that Balo Disease is characterized by bands of intact myelin (the sheath of fatty substances surrounding nerve fibers), alternating with rings of loss of myelin (demyelination), in various parts of the brain and brain stem. The symptoms of Balo Disease vary, according to the areas of the brain that are affected. Symptoms may progress rapidly over several weeks or more slowly over two to three years. | 140 | Balo Disease |
nord_140_1 | Symptoms of Balo Disease | Most cases are characterized by the gradual onset of symptoms that might be found in the more common type of MS, including muscle spasms and paralysis. Other neurological symptoms develop depending on the areas of the brain that are affected and may include intellectual impairment and/or physiological abnormalities. However, in its most serious form, Balo Disease may also suggest the presence of an infectious disease, starting with a high fever and painful headaches. | Symptoms of Balo Disease. Most cases are characterized by the gradual onset of symptoms that might be found in the more common type of MS, including muscle spasms and paralysis. Other neurological symptoms develop depending on the areas of the brain that are affected and may include intellectual impairment and/or physiological abnormalities. However, in its most serious form, Balo Disease may also suggest the presence of an infectious disease, starting with a high fever and painful headaches. | 140 | Balo Disease |
nord_140_2 | Causes of Balo Disease | The cause of MS and its variants remains unknown. However, some studies indicate that autoimmune factors may play a role in the development of Balo Disease. Autoimmune disorders are caused when the body's natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. | Causes of Balo Disease. The cause of MS and its variants remains unknown. However, some studies indicate that autoimmune factors may play a role in the development of Balo Disease. Autoimmune disorders are caused when the body's natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. | 140 | Balo Disease |
nord_140_3 | Affects of Balo Disease | Balo Disease is a rare disorder that affects males and females in equal numbers. More cases have been reported from China and the Philippines than elsewhere. | Affects of Balo Disease. Balo Disease is a rare disorder that affects males and females in equal numbers. More cases have been reported from China and the Philippines than elsewhere. | 140 | Balo Disease |
nord_140_4 | Related disorders of Balo Disease | Symptoms of the following disorders can be similar to those of Balo Disease. Comparisons may be useful for a differential diagnosis:Adrenoleukodystrophy is a rare inherited metabolic disorder characterized by the loss of the fatty covering (myelin sheath) around nerve fibers in the brain (cerebral demyelination) and the progressive degeneration of the adrenal gland. The symptoms of this disorder may include generalized muscle weakness (hypotonia), exaggerated reflex responses (hyperreflexia), impaired ability to coordinate movement (ataxia), spastic partial paralysis, and/or tingling or burning sensations in the arms or legs. (For more information on this disorder, choose “Adrenoleukodystrophy” as your search term in the Rare Disease Database.)Multiple Sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering that surrounds nerve fibers (myelin sheath). The course of the disease is variable. It may advance, relapse, remit, and/or stabilize. Symptoms may include double vision (diplopia), involuntary rhythmic movements of the eyes (nystagmus), speech impairment, numbness in the arms and legs, and/or difficulty walking. Impaired function of the bowel and bladder may also be present. (For more information on this disorder, choose “Multiple Sclerosis” as your search term in the Rare Disease Database.)Canavan's Leukodystrophy is a rare inherited type of leukodystrophy characterized by the progressive degeneration of the central nervous system. Symptoms may include progressive mental deterioration accompanied by increased muscle tone (hypertonia), poor head control, an enlargement of the brain (megalocephaly), and/or blindness. Symptoms typically begin during infancy. Early symptoms of Canavan's Leukodystrophy may include general lack of interest in daily living (apathy), muscle weakness and floppiness (hypotonia), and the loss of previously acquired mental and motor skills. As the disease progresses, there may be spastic muscle contractions of the arms and legs, lack of muscle strength in the neck, swelling of the brain (megalocephaly), and paralysis. (For more information on this disorder, choose “Canavan” as your search term in the Rare Disease Database.)Metachromatic Leukodystrophy (MLD) is a rare inherited leukodystrophy characterized by the abnormal accumulation of a fatty-like substance known as sulfatide in the tissues of the nervous system and other organs. This results in the loss of the coverings on nerve fibers (myelin sheath). Symptoms may include blindness, convulsions, muscle rigidity hypertonia) and/or motor disturbances that may lead to paralysis and dementia. (For more information on this disorder, choose “Metachromatic Leukodystrophy” as your search term in the Rare Disease Database.)Krabbe's Leukodystrophy is a rare inherited metabolic disorder characterized by the abnormal accumulation of a fatty substance (ceremide galactoside) in the brain. Symptoms develop due to a deficiency of the enzyme galactoside beta-galactosidase. These may include irritability, vomiting, episodes of partial unconsciousness, and/or seizures. There may also be spastic contractions of the legs, difficulty swallowing, and mental deterioration. (For more information on this disorder, choose “Krabbe” as your search term in the Rare Disease Database.)Alexander's Disease is an extremely rare, progressive metabolic disorder which is frequently inherited. It is one of the sub-types of Leukodystrophy. Alexander's Disease is characterized by the loss of fatty layers that cover nerve fibers (demyelination) and the formation of abnormal fibers (Rosenthal) in the brain. The symptoms may include muscle spasms, mental impairment, and/or growth delays. Most infants with Alexander's Disease have an abnormally large head (megalencephaly), failure to thrive, and seizures. (For more information on this disorder, choose “Alexander” as your search term in the Rare Disease Database.) | Related disorders of Balo Disease. Symptoms of the following disorders can be similar to those of Balo Disease. Comparisons may be useful for a differential diagnosis:Adrenoleukodystrophy is a rare inherited metabolic disorder characterized by the loss of the fatty covering (myelin sheath) around nerve fibers in the brain (cerebral demyelination) and the progressive degeneration of the adrenal gland. The symptoms of this disorder may include generalized muscle weakness (hypotonia), exaggerated reflex responses (hyperreflexia), impaired ability to coordinate movement (ataxia), spastic partial paralysis, and/or tingling or burning sensations in the arms or legs. (For more information on this disorder, choose “Adrenoleukodystrophy” as your search term in the Rare Disease Database.)Multiple Sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the covering that surrounds nerve fibers (myelin sheath). The course of the disease is variable. It may advance, relapse, remit, and/or stabilize. Symptoms may include double vision (diplopia), involuntary rhythmic movements of the eyes (nystagmus), speech impairment, numbness in the arms and legs, and/or difficulty walking. Impaired function of the bowel and bladder may also be present. (For more information on this disorder, choose “Multiple Sclerosis” as your search term in the Rare Disease Database.)Canavan's Leukodystrophy is a rare inherited type of leukodystrophy characterized by the progressive degeneration of the central nervous system. Symptoms may include progressive mental deterioration accompanied by increased muscle tone (hypertonia), poor head control, an enlargement of the brain (megalocephaly), and/or blindness. Symptoms typically begin during infancy. Early symptoms of Canavan's Leukodystrophy may include general lack of interest in daily living (apathy), muscle weakness and floppiness (hypotonia), and the loss of previously acquired mental and motor skills. As the disease progresses, there may be spastic muscle contractions of the arms and legs, lack of muscle strength in the neck, swelling of the brain (megalocephaly), and paralysis. (For more information on this disorder, choose “Canavan” as your search term in the Rare Disease Database.)Metachromatic Leukodystrophy (MLD) is a rare inherited leukodystrophy characterized by the abnormal accumulation of a fatty-like substance known as sulfatide in the tissues of the nervous system and other organs. This results in the loss of the coverings on nerve fibers (myelin sheath). Symptoms may include blindness, convulsions, muscle rigidity hypertonia) and/or motor disturbances that may lead to paralysis and dementia. (For more information on this disorder, choose “Metachromatic Leukodystrophy” as your search term in the Rare Disease Database.)Krabbe's Leukodystrophy is a rare inherited metabolic disorder characterized by the abnormal accumulation of a fatty substance (ceremide galactoside) in the brain. Symptoms develop due to a deficiency of the enzyme galactoside beta-galactosidase. These may include irritability, vomiting, episodes of partial unconsciousness, and/or seizures. There may also be spastic contractions of the legs, difficulty swallowing, and mental deterioration. (For more information on this disorder, choose “Krabbe” as your search term in the Rare Disease Database.)Alexander's Disease is an extremely rare, progressive metabolic disorder which is frequently inherited. It is one of the sub-types of Leukodystrophy. Alexander's Disease is characterized by the loss of fatty layers that cover nerve fibers (demyelination) and the formation of abnormal fibers (Rosenthal) in the brain. The symptoms may include muscle spasms, mental impairment, and/or growth delays. Most infants with Alexander's Disease have an abnormally large head (megalencephaly), failure to thrive, and seizures. (For more information on this disorder, choose “Alexander” as your search term in the Rare Disease Database.) | 140 | Balo Disease |
nord_140_5 | Diagnosis of Balo Disease | Diagnosis of Balo Disease. | 140 | Balo Disease |
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nord_140_6 | Therapies of Balo Disease | Treatment is symptomatic and supportive. Corticosteroids are usually useful in decreasing severity of acute presentations through their anti-inflammatory actions. Treatment to relieve symptoms, such as spasticity, weakness, pain, or ataxia, includes pharmacologic and rehabilitative modalities. | Therapies of Balo Disease. Treatment is symptomatic and supportive. Corticosteroids are usually useful in decreasing severity of acute presentations through their anti-inflammatory actions. Treatment to relieve symptoms, such as spasticity, weakness, pain, or ataxia, includes pharmacologic and rehabilitative modalities. | 140 | Balo Disease |
nord_141_0 | Overview of Bannayan-Riley-Ruvalcaba Syndrome | SummaryBannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder that is present at birth and is characterized by a large head size (macrocephaly), pigmented spots (maculae) on the penis and benign tumors and tumor-like growths in the intestine called hamartomas. Other possible features include multiple vascular malformations, skeletal abnormalities, as well as developmental delay, autism spectrum disorder, and/or intellectual disability. BRRS is inherited in an autosomal dominant pattern.IntroductionBRRS was previously described as three separate conditions: Riley-Smith syndrome, Bannayan-Zonana syndrome and Ruvalcaba-Myhre-Smith syndrome. BRRS is now known to be a component of PTEN hamartoma tumor syndrome when a germline PTEN mutation is also present: https://rarediseases.org/rare-diseases/pten-hamartoma-tumor-syndrome/Approximately 60% of patients with BRRS have an inborn change (mutation) in the PTEN tumor suppressor gene in all cells of their bodies (germline). These patients can be given the diagnosis of PTEN hamartoma tumor syndrome. | Overview of Bannayan-Riley-Ruvalcaba Syndrome. SummaryBannayan-Riley-Ruvalcaba syndrome (BRRS) is a rare genetic disorder that is present at birth and is characterized by a large head size (macrocephaly), pigmented spots (maculae) on the penis and benign tumors and tumor-like growths in the intestine called hamartomas. Other possible features include multiple vascular malformations, skeletal abnormalities, as well as developmental delay, autism spectrum disorder, and/or intellectual disability. BRRS is inherited in an autosomal dominant pattern.IntroductionBRRS was previously described as three separate conditions: Riley-Smith syndrome, Bannayan-Zonana syndrome and Ruvalcaba-Myhre-Smith syndrome. BRRS is now known to be a component of PTEN hamartoma tumor syndrome when a germline PTEN mutation is also present: https://rarediseases.org/rare-diseases/pten-hamartoma-tumor-syndrome/Approximately 60% of patients with BRRS have an inborn change (mutation) in the PTEN tumor suppressor gene in all cells of their bodies (germline). These patients can be given the diagnosis of PTEN hamartoma tumor syndrome. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_1 | Symptoms of Bannayan-Riley-Ruvalcaba Syndrome | Individuals with BRRS have clinical findings that vary from one person to another. They can be separated into different categories: skin, facial differences, skeletal abnormalities, thyroid gland tumors, gastrointestinal tract, central nervous system, ocular abnormalities, muscular system and other findings. Children with BRRS also tend to be bigger and longer at birth and can have blood vessel changes (hemangiomas) which are seen as raised red birthmarks. Growth slows down with age and patients tend to have normal size and height as adults. This is not a complete list of possible findings. Some are found in case reports and are added to the list of possible findings.Macrocephaly is a hallmark for the diagnosis of BRRS (head circumference greater than or equal to the 97th percentile). Hamartomatous polyposis in the gastrointestinal tract (in the colon and rectum) is seen in 35-45% of patients. Hamartomatous polyposis is defined as a disorganized accumulation of cells and their components from the region where they are located.Skin features are extensive in BRRS. Patients may have multiple subcutaneous or visceral (related to the internal organs) lipomas. Spots (hyperpigmented macules) on the skin of the penis are a very characteristic feature (penile lentigines). Other skin features are dark discoloration of the body folds and creases (acanthosis nigricans) and overgrowths of cells on the face called papillomatous papules. Neuromuscular and neurodevelopmental abnormalities are common and can include low muscle tone (hypotonia), delayed psychomotor development, seizures (less commonly), developmental delay, autism spectrum disorder, and/or intellectual disability. Children with BRRS may also have skeletal malformations such as a funnel chest (pectus excavatum) and abnormal side-to-side and/or front-to-back curvature of the spine (scoliosis, kyphosis or kyphoscoliosis if both). They can also have joint hypermobility.Muscular system abnormalities include an abnormal mixture of fat tissue, fibrous tissue and abnormal vessels found inside the muscle (intramuscular lesions). | Symptoms of Bannayan-Riley-Ruvalcaba Syndrome. Individuals with BRRS have clinical findings that vary from one person to another. They can be separated into different categories: skin, facial differences, skeletal abnormalities, thyroid gland tumors, gastrointestinal tract, central nervous system, ocular abnormalities, muscular system and other findings. Children with BRRS also tend to be bigger and longer at birth and can have blood vessel changes (hemangiomas) which are seen as raised red birthmarks. Growth slows down with age and patients tend to have normal size and height as adults. This is not a complete list of possible findings. Some are found in case reports and are added to the list of possible findings.Macrocephaly is a hallmark for the diagnosis of BRRS (head circumference greater than or equal to the 97th percentile). Hamartomatous polyposis in the gastrointestinal tract (in the colon and rectum) is seen in 35-45% of patients. Hamartomatous polyposis is defined as a disorganized accumulation of cells and their components from the region where they are located.Skin features are extensive in BRRS. Patients may have multiple subcutaneous or visceral (related to the internal organs) lipomas. Spots (hyperpigmented macules) on the skin of the penis are a very characteristic feature (penile lentigines). Other skin features are dark discoloration of the body folds and creases (acanthosis nigricans) and overgrowths of cells on the face called papillomatous papules. Neuromuscular and neurodevelopmental abnormalities are common and can include low muscle tone (hypotonia), delayed psychomotor development, seizures (less commonly), developmental delay, autism spectrum disorder, and/or intellectual disability. Children with BRRS may also have skeletal malformations such as a funnel chest (pectus excavatum) and abnormal side-to-side and/or front-to-back curvature of the spine (scoliosis, kyphosis or kyphoscoliosis if both). They can also have joint hypermobility.Muscular system abnormalities include an abnormal mixture of fat tissue, fibrous tissue and abnormal vessels found inside the muscle (intramuscular lesions). | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_2 | Causes of Bannayan-Riley-Ruvalcaba Syndrome | Approximately 60% of patients with BRRS have an inborn change (mutation) in the PTEN tumor suppressor gene in all cells of their bodies. A tumor suppressor is a gene that slows down cell division, repairs damage to the DNA of cells, and tells cells when to die, a normal process called apoptosis. Mutations in a tumor suppressor gene often lead to overgrowth and/or cancer. The PTEN gene results in the production of an enzyme called phosphatase and tensin homolog (from which the name ‘PTEN’ is derived). PTEN is important for stopping cell growth and starting apoptosis. Researchers believe that the PTEN gene plays a broad role in the development of human cancers. BRRS is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene that first occurs in the affected individual (known as de novo). The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Bannayan-Riley-Ruvalcaba Syndrome. Approximately 60% of patients with BRRS have an inborn change (mutation) in the PTEN tumor suppressor gene in all cells of their bodies. A tumor suppressor is a gene that slows down cell division, repairs damage to the DNA of cells, and tells cells when to die, a normal process called apoptosis. Mutations in a tumor suppressor gene often lead to overgrowth and/or cancer. The PTEN gene results in the production of an enzyme called phosphatase and tensin homolog (from which the name ‘PTEN’ is derived). PTEN is important for stopping cell growth and starting apoptosis. Researchers believe that the PTEN gene plays a broad role in the development of human cancers. BRRS is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene that first occurs in the affected individual (known as de novo). The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_3 | Affects of Bannayan-Riley-Ruvalcaba Syndrome | BRRS was previously reported as three different conditions: Riley-Smith, Bannayan-Zonana and Ruvalcaba-Myhre-Smith syndromes. To facilitate diagnosis and medical care, BRRS is considered to be a component of PTEN hamartoma tumor syndrome (PHTS) for all patients having a germline PTEN mutation. Males and females are affected equally and PHTS is found in all racial and ethnic groups.It is likely that some patients with BRRS remain undiagnosed, making it difficult to determine its true frequency in the general population. | Affects of Bannayan-Riley-Ruvalcaba Syndrome. BRRS was previously reported as three different conditions: Riley-Smith, Bannayan-Zonana and Ruvalcaba-Myhre-Smith syndromes. To facilitate diagnosis and medical care, BRRS is considered to be a component of PTEN hamartoma tumor syndrome (PHTS) for all patients having a germline PTEN mutation. Males and females are affected equally and PHTS is found in all racial and ethnic groups.It is likely that some patients with BRRS remain undiagnosed, making it difficult to determine its true frequency in the general population. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_4 | Related disorders of Bannayan-Riley-Ruvalcaba Syndrome | Symptoms of the following disorders can be similar to those of BRRS. Comparisons may be useful for purposes of formulating a genetic differential diagnosis.There are similarities between BRRS and Cowden syndrome (CS), which is another component of PTEN hamartoma tumor syndrome. One main difference may be an earlier age of diagnosis for BRRS.Juvenile polyposis syndrome (JPS) is characterized by small multiple growths (polyps) within the gastrointestinal system. Symptoms may include gastrointestinal bleeding, abdominal pain, diarrhea, rectal prolapse, collapse of a portion of the bowel into itself and/or gastrointestinal obstruction. Some affected individuals may experience protein loss, malnutrition, and a feeling of general ill health (cachexia). Affected Individuals may have an increased risk of colon cancer. Other symptoms may include clubbing of the finger and toes, failure to thrive and low levels of circulating red blood cells (anemia). JPS is inherited in an autosomal dominant pattern and caused by inborn (germline) mutations in the BMPR1A and SMAD4 genes. Other conditions that are similar to BRRS include Lhermitte-Duclos disease; Peutz-Jeghers syndrome (PJS); Birt-Hogg-Dube syndrome; Proteus syndrome; Gorlin syndrome and neurofibromatosis type 1. | Related disorders of Bannayan-Riley-Ruvalcaba Syndrome. Symptoms of the following disorders can be similar to those of BRRS. Comparisons may be useful for purposes of formulating a genetic differential diagnosis.There are similarities between BRRS and Cowden syndrome (CS), which is another component of PTEN hamartoma tumor syndrome. One main difference may be an earlier age of diagnosis for BRRS.Juvenile polyposis syndrome (JPS) is characterized by small multiple growths (polyps) within the gastrointestinal system. Symptoms may include gastrointestinal bleeding, abdominal pain, diarrhea, rectal prolapse, collapse of a portion of the bowel into itself and/or gastrointestinal obstruction. Some affected individuals may experience protein loss, malnutrition, and a feeling of general ill health (cachexia). Affected Individuals may have an increased risk of colon cancer. Other symptoms may include clubbing of the finger and toes, failure to thrive and low levels of circulating red blood cells (anemia). JPS is inherited in an autosomal dominant pattern and caused by inborn (germline) mutations in the BMPR1A and SMAD4 genes. Other conditions that are similar to BRRS include Lhermitte-Duclos disease; Peutz-Jeghers syndrome (PJS); Birt-Hogg-Dube syndrome; Proteus syndrome; Gorlin syndrome and neurofibromatosis type 1. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_5 | Diagnosis of Bannayan-Riley-Ruvalcaba Syndrome | BRRS may be suspected based upon identification of characteristic physical features (e.g., macrocephaly, penile lentigines, hamartomatous polyposis, characteristic facial abnormalities, skeletal malformations, etc.). The diagnosis may be confirmed by a thorough clinical evaluation and detailed patient and family histories. The diagnosis can also be confirmed when a germline mutation in the PTEN gene is identified. | Diagnosis of Bannayan-Riley-Ruvalcaba Syndrome. BRRS may be suspected based upon identification of characteristic physical features (e.g., macrocephaly, penile lentigines, hamartomatous polyposis, characteristic facial abnormalities, skeletal malformations, etc.). The diagnosis may be confirmed by a thorough clinical evaluation and detailed patient and family histories. The diagnosis can also be confirmed when a germline mutation in the PTEN gene is identified. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_141_6 | Therapies of Bannayan-Riley-Ruvalcaba Syndrome | TreatmentDue to the effects on various organ systems in BRRS, it is important to involve a multidisciplinary team and offer genetic counselling to the patient and their family.Individuals with germline PTEN mutations should undergo cancer surveillance and screening following the National Comprehensive Cancer Network (NCCN) practice guidelines to enable healthcare providers to detect any tumors at the earliest, most treatable stages. For each cancer type, there are specific surveillance guidelines, including when to start screening. Screening does not start at the time of diagnosis for all cancers and depends on the patient’s age at diagnosisPediatric (under age 18)The same surveillance protocol for (malignant) tumors as is currently recommended for Cowden syndrome is also recommended for BRRS. Guidelines are available from the NCCN. This protocol includes hamartoma surveillance from early infancy through yearly hemoglobin tests, yearly surveillance for thyroid cancer from age 7 years, which consists of an ultrasound of thyroid gland as well as annual thyroid palpitation performed by a physician for detection of thyroid nodules. Breast cancer surveillance starts at age of 25 for both males and females, with monthly self-examination as well as a breast exam performed every 6 months with a physician. Urinalysis is also recommended yearly for early detection of kidney cancer (renal carcinoma). However, it is unclear if patients with BRRS without a germline PTEN mutation have the same cancer risks as those who have a germline PTEN mutation. | Therapies of Bannayan-Riley-Ruvalcaba Syndrome. TreatmentDue to the effects on various organ systems in BRRS, it is important to involve a multidisciplinary team and offer genetic counselling to the patient and their family.Individuals with germline PTEN mutations should undergo cancer surveillance and screening following the National Comprehensive Cancer Network (NCCN) practice guidelines to enable healthcare providers to detect any tumors at the earliest, most treatable stages. For each cancer type, there are specific surveillance guidelines, including when to start screening. Screening does not start at the time of diagnosis for all cancers and depends on the patient’s age at diagnosisPediatric (under age 18)The same surveillance protocol for (malignant) tumors as is currently recommended for Cowden syndrome is also recommended for BRRS. Guidelines are available from the NCCN. This protocol includes hamartoma surveillance from early infancy through yearly hemoglobin tests, yearly surveillance for thyroid cancer from age 7 years, which consists of an ultrasound of thyroid gland as well as annual thyroid palpitation performed by a physician for detection of thyroid nodules. Breast cancer surveillance starts at age of 25 for both males and females, with monthly self-examination as well as a breast exam performed every 6 months with a physician. Urinalysis is also recommended yearly for early detection of kidney cancer (renal carcinoma). However, it is unclear if patients with BRRS without a germline PTEN mutation have the same cancer risks as those who have a germline PTEN mutation. | 141 | Bannayan-Riley-Ruvalcaba Syndrome |
nord_142_0 | Overview of Banti’s Syndrome | Banti syndrome is a disorder of the spleen, the large, gland-like organ in the upper left side of the abdomen that produces red blood cells before birth and, in newborns, removes and destroys aged red blood cells, and plays a role in fighting infection. In the case of Banti syndrome, the spleen rapidly but prematurely destroys blood cells.This syndrome is characterized by abnormal enlargement of the spleen (splenomegaly) due to obstruction of blood flow in some veins and abnormally increased blood pressure (hypertension) within the veins of the liver (e.g., hepatic or portal veins), or the spleen (splenic veins). The disorder may be due to any number of different factors causing obstruction of portal, hepatic, or splenic veins including abnormalities present at birth (congenital) of such veins, blood clots, or various underlying disorders causing inflammation and obstruction of veins (vascular obstruction) of the liver. | Overview of Banti’s Syndrome. Banti syndrome is a disorder of the spleen, the large, gland-like organ in the upper left side of the abdomen that produces red blood cells before birth and, in newborns, removes and destroys aged red blood cells, and plays a role in fighting infection. In the case of Banti syndrome, the spleen rapidly but prematurely destroys blood cells.This syndrome is characterized by abnormal enlargement of the spleen (splenomegaly) due to obstruction of blood flow in some veins and abnormally increased blood pressure (hypertension) within the veins of the liver (e.g., hepatic or portal veins), or the spleen (splenic veins). The disorder may be due to any number of different factors causing obstruction of portal, hepatic, or splenic veins including abnormalities present at birth (congenital) of such veins, blood clots, or various underlying disorders causing inflammation and obstruction of veins (vascular obstruction) of the liver. | 142 | Banti’s Syndrome |
nord_142_1 | Symptoms of Banti’s Syndrome | In early stages, symptoms of Banti syndrome include weakness, fatigue, anemia , and abnormal enlargement of the spleen. As the disorder progresses, the anemia becomes more severe. The anemia may be aggravated by a bleeding esophagus that may cause vomiting of blood and the passage of dark stools composed of decomposing blood. Ultimately, in some cases, the liver itself becomes enlarged and subdivided by fibrous tissue (cirrhosis). However, the spleen enlargement in Banti syndrome is the primary symptom.Patients with Banti syndrome bruise easily, are more likely to contract bacterial infections and carry a fever for longer periods of time.Symptoms may also include abnormal accumulation of fluid in the abdominal cavity (ascites), weakness, fatigue; abnormally low levels of circulating red blood cells (anemia), white blood cells (leukopenia), and/or platelets (thrombocytopenia), and/or episodes of bleeding (hemorrhage) from the gastrointestinal tract. | Symptoms of Banti’s Syndrome. In early stages, symptoms of Banti syndrome include weakness, fatigue, anemia , and abnormal enlargement of the spleen. As the disorder progresses, the anemia becomes more severe. The anemia may be aggravated by a bleeding esophagus that may cause vomiting of blood and the passage of dark stools composed of decomposing blood. Ultimately, in some cases, the liver itself becomes enlarged and subdivided by fibrous tissue (cirrhosis). However, the spleen enlargement in Banti syndrome is the primary symptom.Patients with Banti syndrome bruise easily, are more likely to contract bacterial infections and carry a fever for longer periods of time.Symptoms may also include abnormal accumulation of fluid in the abdominal cavity (ascites), weakness, fatigue; abnormally low levels of circulating red blood cells (anemia), white blood cells (leukopenia), and/or platelets (thrombocytopenia), and/or episodes of bleeding (hemorrhage) from the gastrointestinal tract. | 142 | Banti’s Syndrome |
nord_142_2 | Causes of Banti’s Syndrome | Banti syndrome may occur due to a number of different factors causing obstruction of, and abnormally increased blood pressure (hypertension) within, certain veins of the spleen (splenic veins) or the liver (e.g., hepatic or portal veins). These may include abnormalities present at birth (congenital) of such veins, blood clots, or various underlying disorders causing inflammation and obstruction of veins (vascular obstruction) of the liver, such as cirrhosis. Increased arsenic intake has also been implicated in some cases. Also, cases have occurred in patients taking long-term azathioprine, particularly after kidney transplantation. | Causes of Banti’s Syndrome. Banti syndrome may occur due to a number of different factors causing obstruction of, and abnormally increased blood pressure (hypertension) within, certain veins of the spleen (splenic veins) or the liver (e.g., hepatic or portal veins). These may include abnormalities present at birth (congenital) of such veins, blood clots, or various underlying disorders causing inflammation and obstruction of veins (vascular obstruction) of the liver, such as cirrhosis. Increased arsenic intake has also been implicated in some cases. Also, cases have occurred in patients taking long-term azathioprine, particularly after kidney transplantation. | 142 | Banti’s Syndrome |
nord_142_3 | Affects of Banti’s Syndrome | Banti syndrome affects males and females equally. It is relatively common in parts of India and Japan, but rare in Western countries. Increased arsenic levels are present in drinking water in some countries and may contribute to regional differences in incidence. | Affects of Banti’s Syndrome. Banti syndrome affects males and females equally. It is relatively common in parts of India and Japan, but rare in Western countries. Increased arsenic levels are present in drinking water in some countries and may contribute to regional differences in incidence. | 142 | Banti’s Syndrome |
nord_142_4 | Related disorders of Banti’s Syndrome | Symptoms of the following disorders can be similar to those of Banti syndrome. Comparisons may be useful for a differential diagnosis:Primary biliary cirrhosis is a chronic, progressive liver disorder that primarily affects females and typically becomes apparent during middle age. Obstruction of the small bile ducts is accompanied by yellow discoloration of the skin (jaundice). Excessive amounts of copper accumulate in the liver, and fibrous or granular hardening (induration) of the soft liver tissue develops. Although the exact cause of primary biliary cirrhosis is unknown, possible immunological, autoimmune, genetic, and/or environmental factors are under investigation as potential causes of the disorder. (For more information on this disorder, choose “Cirrhosis, Primary Biliary” as your search term in the Rare Disease Database.)Gaucher disease is a rare, inherited metabolic disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids) throughout the body, especially within the bone marrow, spleen and liver. The symptoms and physical findings associated with Gaucher disease vary greatly from case to case, but may include: an abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of circulating red blood cells (anemia), low levels of platelets (thrombocytopenia), and skeletal abnormalities. (For more information on this disorder, choose “Gaucher Disease” as your search term in the Rare Disease Database.)Felty syndrome is a rare form of rheumatoid arthritis, a disorder characterized by painful, stiff, and swollen joints. Major symptoms and physical findings of Felty syndrome include an unusually large spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutophils [neutropenia]). As a result of neutropenia, affected individuals may have an increased susceptibility to certain infections. Other symptoms associated with Felty syndrome may include fatigue, fever, weight loss, and/or discoloration of patches of skin (brown pigmentation). The exact cause of Felty syndrome is unknown. It is believed to be an autoimmune disorder. (For more information on this disorder, choose “Felty Syndrome” as your search term in the Rare Disease Database.) | Related disorders of Banti’s Syndrome. Symptoms of the following disorders can be similar to those of Banti syndrome. Comparisons may be useful for a differential diagnosis:Primary biliary cirrhosis is a chronic, progressive liver disorder that primarily affects females and typically becomes apparent during middle age. Obstruction of the small bile ducts is accompanied by yellow discoloration of the skin (jaundice). Excessive amounts of copper accumulate in the liver, and fibrous or granular hardening (induration) of the soft liver tissue develops. Although the exact cause of primary biliary cirrhosis is unknown, possible immunological, autoimmune, genetic, and/or environmental factors are under investigation as potential causes of the disorder. (For more information on this disorder, choose “Cirrhosis, Primary Biliary” as your search term in the Rare Disease Database.)Gaucher disease is a rare, inherited metabolic disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids) throughout the body, especially within the bone marrow, spleen and liver. The symptoms and physical findings associated with Gaucher disease vary greatly from case to case, but may include: an abnormally enlarged liver and/or spleen (hepatosplenomegaly), low levels of circulating red blood cells (anemia), low levels of platelets (thrombocytopenia), and skeletal abnormalities. (For more information on this disorder, choose “Gaucher Disease” as your search term in the Rare Disease Database.)Felty syndrome is a rare form of rheumatoid arthritis, a disorder characterized by painful, stiff, and swollen joints. Major symptoms and physical findings of Felty syndrome include an unusually large spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutophils [neutropenia]). As a result of neutropenia, affected individuals may have an increased susceptibility to certain infections. Other symptoms associated with Felty syndrome may include fatigue, fever, weight loss, and/or discoloration of patches of skin (brown pigmentation). The exact cause of Felty syndrome is unknown. It is believed to be an autoimmune disorder. (For more information on this disorder, choose “Felty Syndrome” as your search term in the Rare Disease Database.) | 142 | Banti’s Syndrome |
nord_142_5 | Diagnosis of Banti’s Syndrome | The diagnosis of Banti syndrome my be confirmed by a thorough clinical evaluation and a variety of specialized tests, particularly advanced imaging techniques such as a splenic venography and magnetic resonance imaging (MRI). During MRI, a magnetic field and radio waves are used to create cross-sectional images of targeted parts of the body. | Diagnosis of Banti’s Syndrome. The diagnosis of Banti syndrome my be confirmed by a thorough clinical evaluation and a variety of specialized tests, particularly advanced imaging techniques such as a splenic venography and magnetic resonance imaging (MRI). During MRI, a magnetic field and radio waves are used to create cross-sectional images of targeted parts of the body. | 142 | Banti’s Syndrome |
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