id
stringlengths 8
11
| title
stringlengths 14
124
| content
stringlengths 0
34k
| contents
stringlengths 20
34k
| nordid
int64 0
1.32k
| rare-disease
stringlengths 4
103
|
|---|---|---|---|---|---|
nord_1100_0
|
Overview of Scott Craniodigital Syndrome
|
Scott craniodigital syndrome is a condition that has only been found in two families. The manifestations include unusual head shape, growth and developmental delay, and mild webbing between the fingers and toes (syndactyly)
|
Overview of Scott Craniodigital Syndrome. Scott craniodigital syndrome is a condition that has only been found in two families. The manifestations include unusual head shape, growth and developmental delay, and mild webbing between the fingers and toes (syndactyly)
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1100_1
|
Symptoms of Scott Craniodigital Syndrome
|
Individuals with Scott craniodigital syndrome have a combination of mental and growth retardation, minor craniofacial anomalies, and mild webbing between the fingers and toes. Birth weight and length are typically within normal limits, but subsequent growth retardation occurs.Affected individuals have a broad, short head (brachycephaly). In addition, they have long eyelashes, a small chin, a small and pointed nose, and a thin upper lip. Partial soft tissue webbing occurs between fingers two and four and between toes two and three. Affected children may also exhibit incomplete closure of bones in the spinal column surrounding the spinal cord (spina bifida occulta). The severity of the condition depends upon whether there is involvement of the spinal cord in the affected area.There is moderate developmental delay, with children generally walking after age two years. Speech occurs, but is also delayed.
|
Symptoms of Scott Craniodigital Syndrome. Individuals with Scott craniodigital syndrome have a combination of mental and growth retardation, minor craniofacial anomalies, and mild webbing between the fingers and toes. Birth weight and length are typically within normal limits, but subsequent growth retardation occurs.Affected individuals have a broad, short head (brachycephaly). In addition, they have long eyelashes, a small chin, a small and pointed nose, and a thin upper lip. Partial soft tissue webbing occurs between fingers two and four and between toes two and three. Affected children may also exhibit incomplete closure of bones in the spinal column surrounding the spinal cord (spina bifida occulta). The severity of the condition depends upon whether there is involvement of the spinal cord in the affected area.There is moderate developmental delay, with children generally walking after age two years. Speech occurs, but is also delayed.
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1100_2
|
Causes of Scott Craniodigital Syndrome
|
Scott craniodigital syndrome is believed to be inherited as an X-linked recessive genetic trait, based on the presence of the condition in males only. Carrier females have very mild manifestations. Only two families have been described with the condition, so the true gene frequency is unknown. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. All individuals carry 4-5 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. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. In females who inherit a single copy of the disease gene for Scott craniodigital syndrome (heterozygotes), disease traits on the X chromosome may not always be masked by the normal gene on the other X chromosome; as a result, these females may exhibit some of the symptoms associated with this disorder. Heterozygous is a condition in which a person has two different genes (alleles) at the same place on matched chromosomes. An individual who is heterozygous for a particular trait has inherited a gene for that trait from one parent and the alternative gene from the other parent. An individual heterozygous for a hereditary disorder produced by a recessive gene will not show the disease or will have a milder form.
|
Causes of Scott Craniodigital Syndrome. Scott craniodigital syndrome is believed to be inherited as an X-linked recessive genetic trait, based on the presence of the condition in males only. Carrier females have very mild manifestations. Only two families have been described with the condition, so the true gene frequency is unknown. 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 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females. All individuals carry 4-5 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. X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son. In females who inherit a single copy of the disease gene for Scott craniodigital syndrome (heterozygotes), disease traits on the X chromosome may not always be masked by the normal gene on the other X chromosome; as a result, these females may exhibit some of the symptoms associated with this disorder. Heterozygous is a condition in which a person has two different genes (alleles) at the same place on matched chromosomes. An individual who is heterozygous for a particular trait has inherited a gene for that trait from one parent and the alternative gene from the other parent. An individual heterozygous for a hereditary disorder produced by a recessive gene will not show the disease or will have a milder form.
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1100_3
|
Affects of Scott Craniodigital Syndrome
|
Scott Craniodigital Syndrome With Mental Retardation is an extremely rare inherited disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder. The disorder has been reported in two separate families (kindreds) in the medical literature. Most of the symptoms are apparent at birth.
|
Affects of Scott Craniodigital Syndrome. Scott Craniodigital Syndrome With Mental Retardation is an extremely rare inherited disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder. The disorder has been reported in two separate families (kindreds) in the medical literature. Most of the symptoms are apparent at birth.
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1100_4
|
Related disorders of Scott Craniodigital Syndrome
|
Chitayat syndrome refers to a birth defect that combines unusual facial features in association with a malformation of the intestine. The head may broad and short with a high forehead and heavy bones over the eyes, which are abnormally widely spaced (telecanthus). Filippi syndrome (also known as syndactyly, type I, with microcephaly and mental retardation) is a very rare disorder characterized by webbing of the fingers and toes; permanent bending of one or more fingers (clinodactyly); an abnormally small head (microcephaly); an unusual facial appearance that may include a wide forehead with excessive hair growth; and/or mild to severe mental and physical retardation. (For more information on this disorder, choose “Filippi” as your search term in the Rare Disease Database.)Woods syndrome involves prenatal growth retardation, an unusually small head (microcephaly), mental retardation and moderate webbing between the fingers of the hands (syndactyly). Minor facial anomalies may include loss of elasticity of the veins of the eye (varicose veins) and, less frequently, optic atrophy. The lips are thin and the tongue moves awkwardly. Accessory nipples may be present. Toes may be long and slender (brachyclinodactyly). In the heart, the wall separating the ventricles (septum) may be defective.Zerres syndrome is a craniodigital anomaly, the cause of which is unknown, but which is characterized by a small head, small jaws, cross-eyedness (strabismus), and upwardly turned nostrils in a pug-face. Webbing may be found between the fingers and toes. A club foot is common as is the ability of the hip to slip out of its joint easily. Muscle weakness (hypotonia) is common and seizures are not uncommon. The wall separating the atria of the heart may be defective with consequent leakage of blood from one to another. In addition to deafness, both of mental and physical growth is retarded.
|
Related disorders of Scott Craniodigital Syndrome. Chitayat syndrome refers to a birth defect that combines unusual facial features in association with a malformation of the intestine. The head may broad and short with a high forehead and heavy bones over the eyes, which are abnormally widely spaced (telecanthus). Filippi syndrome (also known as syndactyly, type I, with microcephaly and mental retardation) is a very rare disorder characterized by webbing of the fingers and toes; permanent bending of one or more fingers (clinodactyly); an abnormally small head (microcephaly); an unusual facial appearance that may include a wide forehead with excessive hair growth; and/or mild to severe mental and physical retardation. (For more information on this disorder, choose “Filippi” as your search term in the Rare Disease Database.)Woods syndrome involves prenatal growth retardation, an unusually small head (microcephaly), mental retardation and moderate webbing between the fingers of the hands (syndactyly). Minor facial anomalies may include loss of elasticity of the veins of the eye (varicose veins) and, less frequently, optic atrophy. The lips are thin and the tongue moves awkwardly. Accessory nipples may be present. Toes may be long and slender (brachyclinodactyly). In the heart, the wall separating the ventricles (septum) may be defective.Zerres syndrome is a craniodigital anomaly, the cause of which is unknown, but which is characterized by a small head, small jaws, cross-eyedness (strabismus), and upwardly turned nostrils in a pug-face. Webbing may be found between the fingers and toes. A club foot is common as is the ability of the hip to slip out of its joint easily. Muscle weakness (hypotonia) is common and seizures are not uncommon. The wall separating the atria of the heart may be defective with consequent leakage of blood from one to another. In addition to deafness, both of mental and physical growth is retarded.
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1100_5
|
Diagnosis of Scott Craniodigital Syndrome
|
Diagnosis of Scott Craniodigital Syndrome.
| 1,100 |
Scott Craniodigital Syndrome
|
|
nord_1100_6
|
Therapies of Scott Craniodigital Syndrome
|
Scott Craniodigital Syndrome With Mental Retardation may be diagnosed at birth, based upon a thorough clinical evaluation and identification of characteristic physical findings.The treatment of this disorder is directed toward the specific symptoms apparent in each individual. Treatment may require the efforts of a team of specialists who will work together to systematically and comprehensively plan an affected child's treatment. Such specialists may include pediatricians, specialists who diagnose and treat skeletal disorders (orthopedists), neurologists, orthopedic and plastic surgeons, physical and occupational therapists, and/or other healthcare professionals.Specific therapies for the treatment of this disorder are symptomatic and supportive. For example, in some cases, surgery may be performed to correct certain craniofacial abnormalities. In addition, various orthopedic techniques may be used to help treat and/or correct the foot deformity (talipes varus) associated with this syndrome.Early intervention is important in ensuring that children with Scott Craniodigital Syndrome With Mental Retardation reach their potential. Services that may be beneficial may include special remedial education, vocational training, and other medical and/or social services.Genetic counseling will also be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
|
Therapies of Scott Craniodigital Syndrome. Scott Craniodigital Syndrome With Mental Retardation may be diagnosed at birth, based upon a thorough clinical evaluation and identification of characteristic physical findings.The treatment of this disorder is directed toward the specific symptoms apparent in each individual. Treatment may require the efforts of a team of specialists who will work together to systematically and comprehensively plan an affected child's treatment. Such specialists may include pediatricians, specialists who diagnose and treat skeletal disorders (orthopedists), neurologists, orthopedic and plastic surgeons, physical and occupational therapists, and/or other healthcare professionals.Specific therapies for the treatment of this disorder are symptomatic and supportive. For example, in some cases, surgery may be performed to correct certain craniofacial abnormalities. In addition, various orthopedic techniques may be used to help treat and/or correct the foot deformity (talipes varus) associated with this syndrome.Early intervention is important in ensuring that children with Scott Craniodigital Syndrome With Mental Retardation reach their potential. Services that may be beneficial may include special remedial education, vocational training, and other medical and/or social services.Genetic counseling will also be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
| 1,100 |
Scott Craniodigital Syndrome
|
nord_1101_0
|
Overview of Seckel Syndrome
|
Seckel syndrome is rare genetic condition with slow growth before birth (intrauterine growth restriction) resulting in low birth weight. Slow growth continues after birth (postnatal), causing short height (dwarfism). Some features of Seckel syndrome are a small head (microcephaly) and intellectual disability. Possible facial features are a sloping forehead and “beak-like” nose. Other features may include large eyes, a narrow face, ears of a different shape and/or a small jaw (micrognathia). In addition, some affected infants may have curving of the pinkie finger (clinodactyly) or unusual development of the hips (hip dysplasia). They may also have dislocation of a bone in the forearm (radial dislocation) and/or other physical features.
|
Overview of Seckel Syndrome. Seckel syndrome is rare genetic condition with slow growth before birth (intrauterine growth restriction) resulting in low birth weight. Slow growth continues after birth (postnatal), causing short height (dwarfism). Some features of Seckel syndrome are a small head (microcephaly) and intellectual disability. Possible facial features are a sloping forehead and “beak-like” nose. Other features may include large eyes, a narrow face, ears of a different shape and/or a small jaw (micrognathia). In addition, some affected infants may have curving of the pinkie finger (clinodactyly) or unusual development of the hips (hip dysplasia). They may also have dislocation of a bone in the forearm (radial dislocation) and/or other physical features.
| 1,101 |
Seckel Syndrome
|
nord_1101_1
|
Symptoms of Seckel Syndrome
|
Seckel syndrome presents with slow growth during fetal development (intrauterine growth restriction). This results in low birth weight. Slow growth (growth retardation and delayed bone maturation) continues after birth (postnatal). This can lead to short height (dwarfism) with arms and legs that are proportionate to height. (This is different than short height with small arms and legs). Moderate to severe intellectual disability mayalso be present at birth, but may not be obvious until the child is older. Some individuals with Seckel syndrome have kidneys in the wrong place (ectopic kidneys).In addition, infants with Seckel syndrome have differences of the head and face (craniofacial). Most affected infants have small heads (microcepahly) for their age, sex, and body size. Individuals can also have a forehead that slopes backward (receding) and a small jaw (micrognathia) that is farther back than usual (retrognathia). They may also have a curved, triangular “beak-like” nose. Due to these differences, the middle portion of the face may appear to stick out more. In some children, spaces between the bones of the skull (cranial sutures) may close earlier than they should (craniosynostosis). As a result, the head may look long or shortened, depending on which part of the skull is affected.Some infants with Seckel syndrome have other features including large eyes with downward slanting eyelid folds (palpebral fissures). They may have crossed eyes (strabismus). They can also have low-set, differently shaped (dysplastic) ears without ear lobes, and/or a high-arched roof of the mouth (palate) that may be not be formed completely (cleft palate). In some patients, one side of the face may look larger than the other (facial asymmetry). Some affected infants and children may have weak tooth enamel, and differences in the number, and/or positioning of the teeth.Children with Seckel syndrome may have skeletal changes like the lower end of the bone on the thumb side of the hand being out of place (radial dislocation). They may also have elbows or hips that pop out of place, and/or unusual development (dysplasia) of the hips. Some children are not able to fully extend their knees. They may also have cone-shaped ends of bones. Some affected children may develop front-to-back and/or side-to-side curvature of the spine (kyphoscoliosis). An additional skeletal feature may be permanent curving of the pinkie finger stuck in place (clinodactyly). Children can have a twisted position of the foot (clubfoot), flat feet (pes planus) and/or be missing a pair of ribs (11 pairs instead of 12).Males with Seckel syndrome may have testes that do not lower properly (cryptorchidism). Affected females may have a large clitoris (clitoromegaly). In addition, affected children may have increased body hair (hirsutism). Another possible feature is a single, deep crease across the palms of the hands (single palmar crease).Some people with Seckel syndrome may have blood (hematological) problems. These include a reduced amount of all parts of bone marrow including red blood cells, white blood cells, and platelets (pancytopenia). A low level of red blood cells is known as anemia.
|
Symptoms of Seckel Syndrome. Seckel syndrome presents with slow growth during fetal development (intrauterine growth restriction). This results in low birth weight. Slow growth (growth retardation and delayed bone maturation) continues after birth (postnatal). This can lead to short height (dwarfism) with arms and legs that are proportionate to height. (This is different than short height with small arms and legs). Moderate to severe intellectual disability mayalso be present at birth, but may not be obvious until the child is older. Some individuals with Seckel syndrome have kidneys in the wrong place (ectopic kidneys).In addition, infants with Seckel syndrome have differences of the head and face (craniofacial). Most affected infants have small heads (microcepahly) for their age, sex, and body size. Individuals can also have a forehead that slopes backward (receding) and a small jaw (micrognathia) that is farther back than usual (retrognathia). They may also have a curved, triangular “beak-like” nose. Due to these differences, the middle portion of the face may appear to stick out more. In some children, spaces between the bones of the skull (cranial sutures) may close earlier than they should (craniosynostosis). As a result, the head may look long or shortened, depending on which part of the skull is affected.Some infants with Seckel syndrome have other features including large eyes with downward slanting eyelid folds (palpebral fissures). They may have crossed eyes (strabismus). They can also have low-set, differently shaped (dysplastic) ears without ear lobes, and/or a high-arched roof of the mouth (palate) that may be not be formed completely (cleft palate). In some patients, one side of the face may look larger than the other (facial asymmetry). Some affected infants and children may have weak tooth enamel, and differences in the number, and/or positioning of the teeth.Children with Seckel syndrome may have skeletal changes like the lower end of the bone on the thumb side of the hand being out of place (radial dislocation). They may also have elbows or hips that pop out of place, and/or unusual development (dysplasia) of the hips. Some children are not able to fully extend their knees. They may also have cone-shaped ends of bones. Some affected children may develop front-to-back and/or side-to-side curvature of the spine (kyphoscoliosis). An additional skeletal feature may be permanent curving of the pinkie finger stuck in place (clinodactyly). Children can have a twisted position of the foot (clubfoot), flat feet (pes planus) and/or be missing a pair of ribs (11 pairs instead of 12).Males with Seckel syndrome may have testes that do not lower properly (cryptorchidism). Affected females may have a large clitoris (clitoromegaly). In addition, affected children may have increased body hair (hirsutism). Another possible feature is a single, deep crease across the palms of the hands (single palmar crease).Some people with Seckel syndrome may have blood (hematological) problems. These include a reduced amount of all parts of bone marrow including red blood cells, white blood cells, and platelets (pancytopenia). A low level of red blood cells is known as anemia.
| 1,101 |
Seckel Syndrome
|
nord_1101_2
|
Causes of Seckel Syndrome
|
Seckel syndrome is rare genetic disorder that is inherited in an autosomal recessive pattern. There are multiple types of Seckel syndrome caused by harmful changes in genes (mutations) on multiple chromosomes. The types and gene names are:· Seckel syndrome 1: ataxia-telangiectasia and Rad3-related protein (ATR) gene· Seckel syndrome 2: RB binding protein 8 (RBBP8) gene· Seckel syndrome 4: centromere protein J (CENPJ) gene· Seckel syndrome 5: centrosomal protein 152 (CEP152) gene· Seckel syndrome 6: centrosomal protein 63 (CEP63) gene· Seckel syndrome 7: ninein (NIN) gene· Seckel syndrome 8: DNA 2 protein (DNA2) gene· Seckel syndrome 9: ATR interacting protein (ATRIP) gene· Seckel syndrome 10: SMC5-SMC6 complex SUMO ligase (NSMCE2) gene Chromosomes are present in every human cell. Human cells have 23 pairs of chromosomes for a total of 46. One of each pair comes from the father and the other of the pair from the mother. The chromosomes carry our genetic information (genes).The genes provide instructions to make the proteins used by the body. If there is a harmful change (mutation) in the gene, then the protein may not work correctly, or be made in the wrong amount. These changes affect how the body develops and functions.Recessive genetic disorders occur when an individual inherits two non-working genes for the same trait, one from each parent. If an individual receives one working gene and one non-working gene, the person will be a carrier for the disease, but will usually not show symptoms. The risk for two carrier parents to both pass on the non-working gene and 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.All individuals carry a few non-working genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same harmful gene change, which increases the risk to have children with a recessive genetic disorder.
|
Causes of Seckel Syndrome. Seckel syndrome is rare genetic disorder that is inherited in an autosomal recessive pattern. There are multiple types of Seckel syndrome caused by harmful changes in genes (mutations) on multiple chromosomes. The types and gene names are:· Seckel syndrome 1: ataxia-telangiectasia and Rad3-related protein (ATR) gene· Seckel syndrome 2: RB binding protein 8 (RBBP8) gene· Seckel syndrome 4: centromere protein J (CENPJ) gene· Seckel syndrome 5: centrosomal protein 152 (CEP152) gene· Seckel syndrome 6: centrosomal protein 63 (CEP63) gene· Seckel syndrome 7: ninein (NIN) gene· Seckel syndrome 8: DNA 2 protein (DNA2) gene· Seckel syndrome 9: ATR interacting protein (ATRIP) gene· Seckel syndrome 10: SMC5-SMC6 complex SUMO ligase (NSMCE2) gene Chromosomes are present in every human cell. Human cells have 23 pairs of chromosomes for a total of 46. One of each pair comes from the father and the other of the pair from the mother. The chromosomes carry our genetic information (genes).The genes provide instructions to make the proteins used by the body. If there is a harmful change (mutation) in the gene, then the protein may not work correctly, or be made in the wrong amount. These changes affect how the body develops and functions.Recessive genetic disorders occur when an individual inherits two non-working genes for the same trait, one from each parent. If an individual receives one working gene and one non-working gene, the person will be a carrier for the disease, but will usually not show symptoms. The risk for two carrier parents to both pass on the non-working gene and 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.All individuals carry a few non-working genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same harmful gene change, which increases the risk to have children with a recessive genetic disorder.
| 1,101 |
Seckel Syndrome
|
nord_1101_3
|
Affects of Seckel Syndrome
|
Seckel syndrome is a rare genetic disorder that affects males and females in equal numbers. About 1 in 10,000 individuals have Seckel syndrome.
|
Affects of Seckel Syndrome. Seckel syndrome is a rare genetic disorder that affects males and females in equal numbers. About 1 in 10,000 individuals have Seckel syndrome.
| 1,101 |
Seckel Syndrome
|
nord_1101_4
|
Related disorders of Seckel Syndrome
|
Symptoms of the following conditions can be similar to those of Seckel syndrome. Comparisons may be useful to make the correct diagnosis:Seckel syndrome is one of six disorders in the class of dwarfism known as the “primordial dwarfism”. These disorders share similar features. They include skeletal differences (dysplasia) and slow growth before birth (intrauterine growth retardation) and after. This results in varying levels of short height. This group of conditions currently includes five major subtypes: Seckel syndrome, ear-patella-short stature (Meier-Gorlin) syndrome; Russell-Silver syndrome; osteodysplastic primordial dwarfism type I/III; osteodysplastic primordial dwarfism type II.Osteodysplastic primordial dwarfism type II, also known as MOPD II or Majewski osteodysplastic bird-headed dwarfism type II, is a rare genetic condition with shortstature, low birth weight, a small head (microcephaly) and/or skeletal features. Other physical findings may include large eyes, a “beak-like” nose, a pushed back jaw, and/or a narrow face. Slow growth or lack of growth before birth (intrauterine growth deficiency) occurs. Intellectual disability may be present in some patients. Additional symptoms may also occur. Specific symptoms and severity vary from person to person. Osteodysplastic primordial dwarfism type II is inherited in a recessive pattern.
|
Related disorders of Seckel Syndrome. Symptoms of the following conditions can be similar to those of Seckel syndrome. Comparisons may be useful to make the correct diagnosis:Seckel syndrome is one of six disorders in the class of dwarfism known as the “primordial dwarfism”. These disorders share similar features. They include skeletal differences (dysplasia) and slow growth before birth (intrauterine growth retardation) and after. This results in varying levels of short height. This group of conditions currently includes five major subtypes: Seckel syndrome, ear-patella-short stature (Meier-Gorlin) syndrome; Russell-Silver syndrome; osteodysplastic primordial dwarfism type I/III; osteodysplastic primordial dwarfism type II.Osteodysplastic primordial dwarfism type II, also known as MOPD II or Majewski osteodysplastic bird-headed dwarfism type II, is a rare genetic condition with shortstature, low birth weight, a small head (microcephaly) and/or skeletal features. Other physical findings may include large eyes, a “beak-like” nose, a pushed back jaw, and/or a narrow face. Slow growth or lack of growth before birth (intrauterine growth deficiency) occurs. Intellectual disability may be present in some patients. Additional symptoms may also occur. Specific symptoms and severity vary from person to person. Osteodysplastic primordial dwarfism type II is inherited in a recessive pattern.
| 1,101 |
Seckel Syndrome
|
nord_1101_5
|
Diagnosis of Seckel Syndrome
|
Seckel syndrome may be diagnosed before birth (prenatally). Ultrasound can be done to create an image of the developing fetus. Seckel syndrome may be suspected if a fetus has a small head (microcephaly), slow growth or features of the head and face (craniofacial) associated with Seckel syndrome. Sometimes, a diagnosis of Seckel syndrome may not be confirmed until an affected child gets older. More features may be seen with age like intellectual disability or short height.Genetic testing can be done to confirm the diagnosis, either prior to birth or after. If Seckel syndrome is suspected, all of the genes associates with the syndrome should be tested at once (gene panel).Short height associated with Seckel syndrome involves proportional growth of the arms and legs. This allows for differential diagnosis from syndromes that involve short stature and small arms and legs (short-limbed dwarfism).
|
Diagnosis of Seckel Syndrome. Seckel syndrome may be diagnosed before birth (prenatally). Ultrasound can be done to create an image of the developing fetus. Seckel syndrome may be suspected if a fetus has a small head (microcephaly), slow growth or features of the head and face (craniofacial) associated with Seckel syndrome. Sometimes, a diagnosis of Seckel syndrome may not be confirmed until an affected child gets older. More features may be seen with age like intellectual disability or short height.Genetic testing can be done to confirm the diagnosis, either prior to birth or after. If Seckel syndrome is suspected, all of the genes associates with the syndrome should be tested at once (gene panel).Short height associated with Seckel syndrome involves proportional growth of the arms and legs. This allows for differential diagnosis from syndromes that involve short stature and small arms and legs (short-limbed dwarfism).
| 1,101 |
Seckel Syndrome
|
nord_1101_6
|
Therapies of Seckel Syndrome
|
TreatmentMedical treatment for Seckel syndrome is based on the specific problems that are present in the affected child. The child should be treated for the range of features associated with Seckel syndrome, including tooth crowding or position issues, bone dislocations, genital differences and anemia.
|
Therapies of Seckel Syndrome. TreatmentMedical treatment for Seckel syndrome is based on the specific problems that are present in the affected child. The child should be treated for the range of features associated with Seckel syndrome, including tooth crowding or position issues, bone dislocations, genital differences and anemia.
| 1,101 |
Seckel Syndrome
|
nord_1102_0
|
Overview of Segawa Syndrome
|
Segawa syndrome is a rare genetic disorder characterized by an uncoordinated or clumsy manner of walking (abnormal gait) and dystonia. Dystonia is a general term for a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). Dystonia in Segawa syndrome usually affects the legs, but some children may first develop dystonia in the arms. In some cases, usually in adolescents and adults, the symptoms of Segawa syndrome may become noticeably worse or more pronounced in the afternoon and evening than in the morning (marked diurnal fluctuation). The symptoms of Segawa syndrome usually become apparent by around six years of age. Intelligence is not affected. Children with Segawa syndrome usually show a dramatic and sustained improvement when treated with levodopa. Levodopa is an amino acid that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Dopamine is deficient in children with Segawa syndrome. The disorder is caused by mutations of the GCH-1 gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait.
|
Overview of Segawa Syndrome. Segawa syndrome is a rare genetic disorder characterized by an uncoordinated or clumsy manner of walking (abnormal gait) and dystonia. Dystonia is a general term for a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). Dystonia in Segawa syndrome usually affects the legs, but some children may first develop dystonia in the arms. In some cases, usually in adolescents and adults, the symptoms of Segawa syndrome may become noticeably worse or more pronounced in the afternoon and evening than in the morning (marked diurnal fluctuation). The symptoms of Segawa syndrome usually become apparent by around six years of age. Intelligence is not affected. Children with Segawa syndrome usually show a dramatic and sustained improvement when treated with levodopa. Levodopa is an amino acid that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Dopamine is deficient in children with Segawa syndrome. The disorder is caused by mutations of the GCH-1 gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait.
| 1,102 |
Segawa Syndrome
|
nord_1102_1
|
Symptoms of Segawa Syndrome
|
The symptoms and severity of Segawa syndrome can vary greatly from one person to another, even among members of the same family. Symptoms usually become apparent by around six years of age. In some cases, symptoms may not become apparent until later in childhood or even as late as adulthood.The initial symptom of Segawa syndrome is usually an uncoordinated or clumsy manner of walking (abnormal gait) that develops during early childhood because of involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (dystonia). The legs are usually affected first, typically one foot. Dystonia of the foot may force the foot into a twisted posture that resembles clubfoot. Children with Segawa syndrome may fall frequently and display exaggerated reflexes (hyperreflexia) as well.When dystonia affects only one part of the body (e.g., a foot), it is referred to as focal dystonia. Dystonia in Segawa syndrome eventually progresses to legs and then the arms (multifocal dystonia), although it usually remains worse in the legs. In some cases, as a result of dystonia, abnormal curvature of the spine (lordosis) may occur. Without treatment, dystonia gradually progresses over time (approximately 10-15 years) and may eventually affect most of the body (generalized dystonia).The dystonia and associated gait disturbances are usually worse during the afternoon, evening and at night than in the morning, a characteristic finding associated with Segawa syndrome called diurnal fluctuation. In some individuals the symptoms may be less severe in the morning than in the evening; in others the symptoms may be absent in morning and only present during the evening or at night. Although a key finding of Segawa syndrome, diurnal fluctuation does not occur in all cases. It is more lilely to occur in older individuals (adolescents and adults) than in young children. Dystonia and gait disturbances may also worsen following exercise or exertion.Some affected children also develop stiffness (rigidity) and abnormal slowness of movement of the muscles of the arms and legs. The degree of stiffness and slowness of movement may vary greatly. Affected individuals may rapidly fatigue or require abnormal effort when attempting to perform certain tasks. During adolescence, some affected individuals develop a tremor that occurs when attempting to hold a certain position against gravity (postural tremor). Postural tremor usually affects one hand, although it may spread to all the arms and legs and even the neck. The progression of Segawa syndrome usually stops around the fourth decade.When the onset of Segawa syndrome is during adolescence rather than childhood, the symptoms tend to be less severe. Generalized dystonia usually does not develop. When the onset of Segawa syndrome is during adulthood, the symptoms may resemble those found in Parkinson’s disease, which is sometimes referred to as parkinsonism. These symptoms include tremors, abnormal slowness of movement and an inability to remain in a stable or balanced position.In some cases, individuals with Segawa syndrome may develop other forms of dystonia including those affecting the wrist (writer’s cramp), the neck (spasmodic torticollis) or the face and jaw (oromandibular dystonia). Some individuals may develop progressive weakness and increased muscle tone and stiffness (spastic paraplegia) or the spontaneous appearance and disappearance of dystonia and parkinsonism. In rare cases, mood or behavioral symptoms may occur including sleep problems, depression, anxiety or obsessive-compulsive disorder. Some researchers believe that mood and behavioral problems associated with Segawa syndrome are underreported.
|
Symptoms of Segawa Syndrome. The symptoms and severity of Segawa syndrome can vary greatly from one person to another, even among members of the same family. Symptoms usually become apparent by around six years of age. In some cases, symptoms may not become apparent until later in childhood or even as late as adulthood.The initial symptom of Segawa syndrome is usually an uncoordinated or clumsy manner of walking (abnormal gait) that develops during early childhood because of involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (dystonia). The legs are usually affected first, typically one foot. Dystonia of the foot may force the foot into a twisted posture that resembles clubfoot. Children with Segawa syndrome may fall frequently and display exaggerated reflexes (hyperreflexia) as well.When dystonia affects only one part of the body (e.g., a foot), it is referred to as focal dystonia. Dystonia in Segawa syndrome eventually progresses to legs and then the arms (multifocal dystonia), although it usually remains worse in the legs. In some cases, as a result of dystonia, abnormal curvature of the spine (lordosis) may occur. Without treatment, dystonia gradually progresses over time (approximately 10-15 years) and may eventually affect most of the body (generalized dystonia).The dystonia and associated gait disturbances are usually worse during the afternoon, evening and at night than in the morning, a characteristic finding associated with Segawa syndrome called diurnal fluctuation. In some individuals the symptoms may be less severe in the morning than in the evening; in others the symptoms may be absent in morning and only present during the evening or at night. Although a key finding of Segawa syndrome, diurnal fluctuation does not occur in all cases. It is more lilely to occur in older individuals (adolescents and adults) than in young children. Dystonia and gait disturbances may also worsen following exercise or exertion.Some affected children also develop stiffness (rigidity) and abnormal slowness of movement of the muscles of the arms and legs. The degree of stiffness and slowness of movement may vary greatly. Affected individuals may rapidly fatigue or require abnormal effort when attempting to perform certain tasks. During adolescence, some affected individuals develop a tremor that occurs when attempting to hold a certain position against gravity (postural tremor). Postural tremor usually affects one hand, although it may spread to all the arms and legs and even the neck. The progression of Segawa syndrome usually stops around the fourth decade.When the onset of Segawa syndrome is during adolescence rather than childhood, the symptoms tend to be less severe. Generalized dystonia usually does not develop. When the onset of Segawa syndrome is during adulthood, the symptoms may resemble those found in Parkinson’s disease, which is sometimes referred to as parkinsonism. These symptoms include tremors, abnormal slowness of movement and an inability to remain in a stable or balanced position.In some cases, individuals with Segawa syndrome may develop other forms of dystonia including those affecting the wrist (writer’s cramp), the neck (spasmodic torticollis) or the face and jaw (oromandibular dystonia). Some individuals may develop progressive weakness and increased muscle tone and stiffness (spastic paraplegia) or the spontaneous appearance and disappearance of dystonia and parkinsonism. In rare cases, mood or behavioral symptoms may occur including sleep problems, depression, anxiety or obsessive-compulsive disorder. Some researchers believe that mood and behavioral problems associated with Segawa syndrome are underreported.
| 1,102 |
Segawa Syndrome
|
nord_1102_2
|
Causes of Segawa Syndrome
|
Segawa syndrome is caused by mutations of the guanosine triphosphate cyclohydrolase I (GCH-1) gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait or occurs as a spontaneous genetic change (i.e., new mutation) that occurs sporadically for no apparent reason.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.Investigators have determined that the GCH-1 gene is located on the long arm (q) of chromosome 14 (14q22.1-q22.2. 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 14q22.1-22.2″ refers to band 22.1-22.2 on the long arm of chromosome 14. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The GCH-1 gene contains instructions for creating (encoding) an enzyme called guanosine triphosphate cyclohydrolase 1 (GTPCH1). This enzyme is an essential part of the chemical processes that contribute to the development of dopamine in the body. Dopamine is a neurotransmitter, a chemical that modifies, amplifies or transmits nerve impulses from one nerve cell (neuron) to another, enabling nerve cells to communicate. Dopamine is also converted into two additional neurotransmitters called norepinephrine and epinephrine (adrenaline). Dopamine is critical for the proper function of certain processes of the brain especially those that control movement. Mutation of the GCH-1 gene results in deficient levels of the GTPCH1 enzyme, which ultimately results in a deficiency of dopamine.Segawa syndrome is also characterized by variable expressivity and incomplete penetrance. Variable expressivity is when individuals with the same genetic mutation have different symptoms or different severity of symptoms. Incomplete penetrance refers to how some individuals who inherited a mutated gene for a dominant disorder are not affected or are only mildly affected, while others develop the disorder.Segawa syndrome may be classified as a form of dystonia, an inherited neurotransmitter disorder, and a metabolic disorder. Dystonia is a group neuromuscular disorders in which involuntary muscle contractions force the body into abnormal, sometimes painful, movements and positions (postures).Pediatric inherited neurotransmitter disorders are an emerging group of rare disorders characterized by defects in the creation (synthesis) and metabolism of one or more neurotransmitters and result in a variety of neurological and neuromuscular symptoms. The disorders are differentiated by the specific neurotransmitter involved.Segawa syndrome is also be classified as an inborn error of metabolism (metabolic disorder). “Metabolism” refers to all the chemical processes in the body, including the breakdown of complex substances into simpler ones (catabolism), usually with the release of energy, and processes in which complex substances are built up from simpler ones (anabolism), usually resulting in energy consumption. Inborn errors of metabolism result from abnormal functioning of a specific protein or enzyme that accelerates particular chemical activities in the body.
|
Causes of Segawa Syndrome. Segawa syndrome is caused by mutations of the guanosine triphosphate cyclohydrolase I (GCH-1) gene. The GCH-1 gene mutation is inherited as an autosomal dominant trait or occurs as a spontaneous genetic change (i.e., new mutation) that occurs sporadically for no apparent reason.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.Investigators have determined that the GCH-1 gene is located on the long arm (q) of chromosome 14 (14q22.1-q22.2. 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 14q22.1-22.2″ refers to band 22.1-22.2 on the long arm of chromosome 14. The numbered bands specify the location of the thousands of genes that are present on each chromosome.The GCH-1 gene contains instructions for creating (encoding) an enzyme called guanosine triphosphate cyclohydrolase 1 (GTPCH1). This enzyme is an essential part of the chemical processes that contribute to the development of dopamine in the body. Dopamine is a neurotransmitter, a chemical that modifies, amplifies or transmits nerve impulses from one nerve cell (neuron) to another, enabling nerve cells to communicate. Dopamine is also converted into two additional neurotransmitters called norepinephrine and epinephrine (adrenaline). Dopamine is critical for the proper function of certain processes of the brain especially those that control movement. Mutation of the GCH-1 gene results in deficient levels of the GTPCH1 enzyme, which ultimately results in a deficiency of dopamine.Segawa syndrome is also characterized by variable expressivity and incomplete penetrance. Variable expressivity is when individuals with the same genetic mutation have different symptoms or different severity of symptoms. Incomplete penetrance refers to how some individuals who inherited a mutated gene for a dominant disorder are not affected or are only mildly affected, while others develop the disorder.Segawa syndrome may be classified as a form of dystonia, an inherited neurotransmitter disorder, and a metabolic disorder. Dystonia is a group neuromuscular disorders in which involuntary muscle contractions force the body into abnormal, sometimes painful, movements and positions (postures).Pediatric inherited neurotransmitter disorders are an emerging group of rare disorders characterized by defects in the creation (synthesis) and metabolism of one or more neurotransmitters and result in a variety of neurological and neuromuscular symptoms. The disorders are differentiated by the specific neurotransmitter involved.Segawa syndrome is also be classified as an inborn error of metabolism (metabolic disorder). “Metabolism” refers to all the chemical processes in the body, including the breakdown of complex substances into simpler ones (catabolism), usually with the release of energy, and processes in which complex substances are built up from simpler ones (anabolism), usually resulting in energy consumption. Inborn errors of metabolism result from abnormal functioning of a specific protein or enzyme that accelerates particular chemical activities in the body.
| 1,102 |
Segawa Syndrome
|
nord_1102_3
|
Affects of Segawa Syndrome
|
Segawa syndrome affects girls and women more often than boys and men. In sporadic cases (i.e., new mutations), women are affected four times more often than men. Women are also more likely to have severe symptoms than men are. The exact incidence of Segawa syndrome in the general population is unknown. Researchers believe that the disorder is often misdiagnosed or goes undiagnosed, making it difficult to determine its true frequency in the general population. Segawa syndrome and tyrosine hydroxylase deficiency, which is also known as autosomal recessive dopa-responsive dystonia, account for approximately 5-10 percent of all cases of primary dystonia in childhood. Segawa syndrome was first described in the medical literature in 1971. It was originally called hereditary progressive dystonia with marked diurnal fluctuation.
|
Affects of Segawa Syndrome. Segawa syndrome affects girls and women more often than boys and men. In sporadic cases (i.e., new mutations), women are affected four times more often than men. Women are also more likely to have severe symptoms than men are. The exact incidence of Segawa syndrome in the general population is unknown. Researchers believe that the disorder is often misdiagnosed or goes undiagnosed, making it difficult to determine its true frequency in the general population. Segawa syndrome and tyrosine hydroxylase deficiency, which is also known as autosomal recessive dopa-responsive dystonia, account for approximately 5-10 percent of all cases of primary dystonia in childhood. Segawa syndrome was first described in the medical literature in 1971. It was originally called hereditary progressive dystonia with marked diurnal fluctuation.
| 1,102 |
Segawa Syndrome
|
nord_1102_4
|
Related disorders of Segawa Syndrome
|
Symptoms of the following disorders can be similar to those of Segawa syndrome. Comparisons may be useful for a differential diagnosis.Cerebral palsy is a general term that covers a group of disorders that involve impairment of muscle control or coordination resulting from injury to the brain during its early stages of development (the fetal, perinatal or early childhood stages). There may be problems associated with involuntary movements, vision, hearing, communication skills, perception levels, intellect and seizures. Individuals with cerebral palsy often experience delays in reaching developmental milestones. The specific symptoms associated with cerebral palsy vary greatly from case to case. (For more information on this disorder, choose “Cerebral Palsy” as your search term in the Rare Disease Database.)Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by progressive weakness (paraplegia) and increased muscle tone and stiffness (spasticity) of leg muscles. HSP is also sometimes referred to as familial spastic paraplegia (FSP) or Strumpell-Lorraine syndrome. The age at symptom onset and the degree of muscle weakness and spasticity may be extremely variable from case to case, including among individuals within the same family (kindred). Initial findings typically include stiffness and mild weakness of leg muscles, balance difficulties, unexplained tripping and falls, and an unusually “clumsy” manner of walking (gait). As the disorder progresses, walking may become increasingly difficult. However, complete loss of the ability to walk is relatively rare. HSP may be classified into two major subtypes: “uncomplicated” or “complicated” HSP. In individuals with uncomplicated (or “pure”) HSP, progressive spastic paraplegia occurs as an isolated, primary finding. In those with complicated HSP, additional neurologic abnormalities are present. Some individuals with uncomplicated HSP may develop muscle spasms and difficulties with bladder control. In those with complicated HSP, associated symptoms and findings may include visual and/or hearing impairment, mental retardation, impaired control of voluntary movements (ataxia), and/or other abnormalities. According to researchers, changes (mutations) of many different genes may cause HSP. In most cases, such mutations appear to be transmitted as an autosomal dominant trait. (For more information on this disorder, choose “hereditary spastic paraplegia” as your search term in the Rare Disease Database.)Autosomal recessive GTPCH1 deficiency refers to rare cases of GTPCH1 deficiency in which affected individuals inherit the mutated gene from both parents. The recessive form of GTPCH1 deficiency is generally more severe than the dominant form. Affected individuals also have a deficiency of tetrahydrobiopterin, a natural substance (coenzyme) that enhances the action of other enzymes. Tetrahydrobiopterin deficiency results in abnormally high levels of the amino acid phenylalanine in the blood. Associated symptoms include an uncoordinated or clumsy manner of walking (abnormal gait) due to involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (dystonia). Affected individuals may also develop severe neurological dysfunction including seizures, cognitive impairment, swallowing difficulties, diminished muscle tone and delays in the attaining developmental milestones (developmental delays).There are additional metabolic disorders that have been identified in which certain enzyme deficiencies result in disrupted metabolism of a neurotransmitter or neurotransmitters. These disorders include tyrosine hydroxylase deficiency (autosomal recessive dopa-responsive dystonia), aromatic L-amino acid decarboxylase deficiency, sepiapterin reductase deficiency, and succinic semialdehyde dehydrogenase (SSADH). Although associated neurological and neuromuscular symptoms may vary, these disorders may have certain features that are similar to those associated with Segawa syndrome. Such abnormalities may include limb dystonia, mood alterations, and the early onset of Parkinson-like symptoms. Additional findings may include involuntary, rhythmic, quivering movements (tremors) and abnormal slowness of movement (bradykinesia). Evidence suggests that there may be other currently unidentified metabolic disorders resulting in disrupted metabolism of neurotransmitters. (For more information on these disordes, choose the specific disorder name as your search term in the Rare Disease Database.)
|
Related disorders of Segawa Syndrome. Symptoms of the following disorders can be similar to those of Segawa syndrome. Comparisons may be useful for a differential diagnosis.Cerebral palsy is a general term that covers a group of disorders that involve impairment of muscle control or coordination resulting from injury to the brain during its early stages of development (the fetal, perinatal or early childhood stages). There may be problems associated with involuntary movements, vision, hearing, communication skills, perception levels, intellect and seizures. Individuals with cerebral palsy often experience delays in reaching developmental milestones. The specific symptoms associated with cerebral palsy vary greatly from case to case. (For more information on this disorder, choose “Cerebral Palsy” as your search term in the Rare Disease Database.)Hereditary spastic paraplegia (HSP) is a group of inherited neurological disorders characterized by progressive weakness (paraplegia) and increased muscle tone and stiffness (spasticity) of leg muscles. HSP is also sometimes referred to as familial spastic paraplegia (FSP) or Strumpell-Lorraine syndrome. The age at symptom onset and the degree of muscle weakness and spasticity may be extremely variable from case to case, including among individuals within the same family (kindred). Initial findings typically include stiffness and mild weakness of leg muscles, balance difficulties, unexplained tripping and falls, and an unusually “clumsy” manner of walking (gait). As the disorder progresses, walking may become increasingly difficult. However, complete loss of the ability to walk is relatively rare. HSP may be classified into two major subtypes: “uncomplicated” or “complicated” HSP. In individuals with uncomplicated (or “pure”) HSP, progressive spastic paraplegia occurs as an isolated, primary finding. In those with complicated HSP, additional neurologic abnormalities are present. Some individuals with uncomplicated HSP may develop muscle spasms and difficulties with bladder control. In those with complicated HSP, associated symptoms and findings may include visual and/or hearing impairment, mental retardation, impaired control of voluntary movements (ataxia), and/or other abnormalities. According to researchers, changes (mutations) of many different genes may cause HSP. In most cases, such mutations appear to be transmitted as an autosomal dominant trait. (For more information on this disorder, choose “hereditary spastic paraplegia” as your search term in the Rare Disease Database.)Autosomal recessive GTPCH1 deficiency refers to rare cases of GTPCH1 deficiency in which affected individuals inherit the mutated gene from both parents. The recessive form of GTPCH1 deficiency is generally more severe than the dominant form. Affected individuals also have a deficiency of tetrahydrobiopterin, a natural substance (coenzyme) that enhances the action of other enzymes. Tetrahydrobiopterin deficiency results in abnormally high levels of the amino acid phenylalanine in the blood. Associated symptoms include an uncoordinated or clumsy manner of walking (abnormal gait) due to involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (dystonia). Affected individuals may also develop severe neurological dysfunction including seizures, cognitive impairment, swallowing difficulties, diminished muscle tone and delays in the attaining developmental milestones (developmental delays).There are additional metabolic disorders that have been identified in which certain enzyme deficiencies result in disrupted metabolism of a neurotransmitter or neurotransmitters. These disorders include tyrosine hydroxylase deficiency (autosomal recessive dopa-responsive dystonia), aromatic L-amino acid decarboxylase deficiency, sepiapterin reductase deficiency, and succinic semialdehyde dehydrogenase (SSADH). Although associated neurological and neuromuscular symptoms may vary, these disorders may have certain features that are similar to those associated with Segawa syndrome. Such abnormalities may include limb dystonia, mood alterations, and the early onset of Parkinson-like symptoms. Additional findings may include involuntary, rhythmic, quivering movements (tremors) and abnormal slowness of movement (bradykinesia). Evidence suggests that there may be other currently unidentified metabolic disorders resulting in disrupted metabolism of neurotransmitters. (For more information on these disordes, choose the specific disorder name as your search term in the Rare Disease Database.)
| 1,102 |
Segawa Syndrome
|
nord_1102_5
|
Diagnosis of Segawa Syndrome
|
A diagnosis of Segawa syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and a response to therapy with low doses of levodopa. An examination of cerebrospinal fluid (CSF) can detect certain substances that are byproducts of metabolism (metabolites) specifically pterins. Identification of reduced levels of pterins in CSF can help to confirm a diagnosis of Segawa syndrome and distinguish the disorder from related neurotransmitter disorders. A sample of CSF is obtained through a procedure called a spinal tap (lumbar puncture), in which a needle is inserted into the spinal canal in the lower back.A diagnosis of Segawa syndrome can be confirmed through molecular genetic testing, which can reveal the characteristic mutation of the GCH-1gene that causes the disorder. Molecular genetic testing is available on a clinical basis.
|
Diagnosis of Segawa Syndrome. A diagnosis of Segawa syndrome is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings, and a response to therapy with low doses of levodopa. An examination of cerebrospinal fluid (CSF) can detect certain substances that are byproducts of metabolism (metabolites) specifically pterins. Identification of reduced levels of pterins in CSF can help to confirm a diagnosis of Segawa syndrome and distinguish the disorder from related neurotransmitter disorders. A sample of CSF is obtained through a procedure called a spinal tap (lumbar puncture), in which a needle is inserted into the spinal canal in the lower back.A diagnosis of Segawa syndrome can be confirmed through molecular genetic testing, which can reveal the characteristic mutation of the GCH-1gene that causes the disorder. Molecular genetic testing is available on a clinical basis.
| 1,102 |
Segawa Syndrome
|
nord_1102_6
|
Therapies of Segawa Syndrome
|
TreatmentSegawa syndrome is treated with medications to restore normal dopamine levels in the brain. Affected individuals are initially treated with low levels of an amino acid called levodopa (L-dopa) that is converted to dopamine by enzymes in the blood and brain. Dopamine cannot cross the blood-brain barrier, so affected individuals also receive a second medication (usually carbidopa) to prevent conversion of L-dopa to dopamine before it ca. cross the blood-brain barrier. The blood-brain barrier is a protective network of blood vessels and cells that allow some materials to enter the brain, while keeping other materials out.The response to L-dopa therapy varies among affected individuals. Some people respond quickly and completely to L-dopa therapy seeing a full reversal of symptoms. In others, the response may take time and improvement is seen gradually over a few months. In some cases, the dosage of L-dopa used to treat an affected individual may need to be adjusted until a dosage can be achieved that effectively treat the disorder.A small number of individuals with Segawa syndrome may develop a side effect of L-dopa therapy called dyskinesia, which refers to abnormal involuntary movements when performing voluntary movements (dyskinesia). Dyskinesia goes away if the dose of L-dopa is lowered; when the dose is gradually increased later on, dyskinesia usually does not reappear.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
|
Therapies of Segawa Syndrome. TreatmentSegawa syndrome is treated with medications to restore normal dopamine levels in the brain. Affected individuals are initially treated with low levels of an amino acid called levodopa (L-dopa) that is converted to dopamine by enzymes in the blood and brain. Dopamine cannot cross the blood-brain barrier, so affected individuals also receive a second medication (usually carbidopa) to prevent conversion of L-dopa to dopamine before it ca. cross the blood-brain barrier. The blood-brain barrier is a protective network of blood vessels and cells that allow some materials to enter the brain, while keeping other materials out.The response to L-dopa therapy varies among affected individuals. Some people respond quickly and completely to L-dopa therapy seeing a full reversal of symptoms. In others, the response may take time and improvement is seen gradually over a few months. In some cases, the dosage of L-dopa used to treat an affected individual may need to be adjusted until a dosage can be achieved that effectively treat the disorder.A small number of individuals with Segawa syndrome may develop a side effect of L-dopa therapy called dyskinesia, which refers to abnormal involuntary movements when performing voluntary movements (dyskinesia). Dyskinesia goes away if the dose of L-dopa is lowered; when the dose is gradually increased later on, dyskinesia usually does not reappear.Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
| 1,102 |
Segawa Syndrome
|
nord_1103_0
|
Overview of Senior-Løken Syndrome
|
Senior-Løken syndrome (SLS) is a rare disorder belonging to the general group of rare diseases called ciliopathies that result in nephronophthisis and Leber congenital amaurosis. Nephronophthisis is the progressive wasting of the filtering unit of the kidney; it is characterized by cysts that develop in the kidneys during infancy or early childhood. Individuals will also develop symptoms of early-onset retinal dystrophy, a progressive retina disease that damages vision, within the first few years of life. Eventually the individual may experience renal failure and vision loss.SLS is inherited in an autosomal recessive pattern. Currently, ten genes have been linked to the disorder.
|
Overview of Senior-Løken Syndrome. Senior-Løken syndrome (SLS) is a rare disorder belonging to the general group of rare diseases called ciliopathies that result in nephronophthisis and Leber congenital amaurosis. Nephronophthisis is the progressive wasting of the filtering unit of the kidney; it is characterized by cysts that develop in the kidneys during infancy or early childhood. Individuals will also develop symptoms of early-onset retinal dystrophy, a progressive retina disease that damages vision, within the first few years of life. Eventually the individual may experience renal failure and vision loss.SLS is inherited in an autosomal recessive pattern. Currently, ten genes have been linked to the disorder.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_1
|
Symptoms of Senior-Løken Syndrome
|
Senior-Løken syndrome is a rare inherited disorder characterized by progressive kidney and eye problems.NephronophthisisThe onset of nephronophthisis usually occurs within the first year of life or early childhood; it is characterized by fluid-filled cysts that form in the kidneys and progressively worsen. The cysts can damage the kidneys and cause increased urine production (polyuria), weakness and fatigue, and excessive thirst (polydipsia). The kidney problems are present at birth in some families, but for other families, symptoms will develop very gradually before becoming apparent.Renal ultrasound scans may help in the diagnosis showing kidneys of normal size, with increased echogenicity and corticomedullary cysts. As the disease progresses, kidneys become atrophic, and the cysts become more prominent. Progressive failure of kidney function occurs because of degeneration or loss of function of the small collecting tubes (tubules) in the kidney. This can cause chronic interstitial nephritis and uremia.Chronic interstitial nephritis is a kidney syndrome in which the spaces between the tissue of the kidney (interstitial) become inflamed and structural changes occur. Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure.Uremia is a condition that is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood, causing a severe toxic condition. Normally, these by-products of protein breakdown would be passed in the urine.Early-onset retinal dystrophiesEarly-onset retinal dystrophies are a group of disorders characterized by the progressive atrophy of the retina, which is a tissue at the back of the eye that detects color and light. The most severe form is Leber congenital amaurosis (LCA). LCA causes vision problems such as sensitivity to light (photophobia), involuntary movements (nystagmus) and severe farsightedness (hyperopia). A decrease in visual responsiveness at birth is the first sign of this disorder with roving eye movements being apparent in the first few years of life.In some patients with Senior-Løken syndrome the progressive atrophy of the retina of the eye may take a course similar to retinitis pigmentosa. This condition typically becomes apparent later in life with the earliest symptom being difficulty seeing in dimly lit places (night blindness). This is slowly followed by tunnel vision. The rate of progression can vary.Other symptoms have been noted in some families such as diabetes insipidus, neurosensory hearing loss, muscular incoordination caused by disease of the cerebellum in the brain (cerebellar ataxia), abnormal formation of fibrous tissue in the liver (hepatic fibrosis) and skeletal abnormalities.
|
Symptoms of Senior-Løken Syndrome. Senior-Løken syndrome is a rare inherited disorder characterized by progressive kidney and eye problems.NephronophthisisThe onset of nephronophthisis usually occurs within the first year of life or early childhood; it is characterized by fluid-filled cysts that form in the kidneys and progressively worsen. The cysts can damage the kidneys and cause increased urine production (polyuria), weakness and fatigue, and excessive thirst (polydipsia). The kidney problems are present at birth in some families, but for other families, symptoms will develop very gradually before becoming apparent.Renal ultrasound scans may help in the diagnosis showing kidneys of normal size, with increased echogenicity and corticomedullary cysts. As the disease progresses, kidneys become atrophic, and the cysts become more prominent. Progressive failure of kidney function occurs because of degeneration or loss of function of the small collecting tubes (tubules) in the kidney. This can cause chronic interstitial nephritis and uremia.Chronic interstitial nephritis is a kidney syndrome in which the spaces between the tissue of the kidney (interstitial) become inflamed and structural changes occur. Eventually the patient may have symptoms such as nausea, vomiting, weight loss, fatigue, anemia and ultimately kidney failure.Uremia is a condition that is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood, causing a severe toxic condition. Normally, these by-products of protein breakdown would be passed in the urine.Early-onset retinal dystrophiesEarly-onset retinal dystrophies are a group of disorders characterized by the progressive atrophy of the retina, which is a tissue at the back of the eye that detects color and light. The most severe form is Leber congenital amaurosis (LCA). LCA causes vision problems such as sensitivity to light (photophobia), involuntary movements (nystagmus) and severe farsightedness (hyperopia). A decrease in visual responsiveness at birth is the first sign of this disorder with roving eye movements being apparent in the first few years of life.In some patients with Senior-Løken syndrome the progressive atrophy of the retina of the eye may take a course similar to retinitis pigmentosa. This condition typically becomes apparent later in life with the earliest symptom being difficulty seeing in dimly lit places (night blindness). This is slowly followed by tunnel vision. The rate of progression can vary.Other symptoms have been noted in some families such as diabetes insipidus, neurosensory hearing loss, muscular incoordination caused by disease of the cerebellum in the brain (cerebellar ataxia), abnormal formation of fibrous tissue in the liver (hepatic fibrosis) and skeletal abnormalities.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_2
|
Causes of Senior-Løken Syndrome
|
Senior-Løken syndrome is currently known to be caused by changes (pathogenic variants or mutations) in at least 10 genes: NPHP1, INVS /NPHP2, NPHP3, NPHP4, IQCB1/NPHP5, CEP290/NPHP6, SDCCAG8/NPHP10, WDR19/NPHP13, CEP164 and TRAF3IP1.The proteins encoded by these genes play a large role in cell structures called cilia. Cilia are microscopic hair-like structures that stick out from the surface of a cell and are responsible for transmitting information between cells. Cilia are essential for sensory input, since retinal photoreceptors have a cilium connecting outer and inner segments of the cell and there are also cilia in the developing inner ear but are also important for the structure and function of the cells in the kidneys.Variants in one of the above referred genes can lead to problems with the function of cilia, causing disruption of important signaling within cells. Therefore, the damaged cilia are responsible for Senior-Løken syndrome, which is considered as a “ciliopathy “, a heterogeneous group of genetic disorders which affect to 1% of all the rare disease patients and occur due to primary ciliary dysfunction, affecting many parts of the body, including the kidney, eye, liver and brain. However, it is still unclear how they specifically lead to Leber congenital amaurosis and nephronophthisis, and some overlapping between conditions caused by the large group of genes involved in ciliopathies can occur. Other ciliopathies are Bardet Biedl syndrome, Joubert syndrome, Laurence Moon syndrome, McKusick Kaufman syndrome, autosomal dominant and autosomal recessive polycystic kidney disease and Biemond syndrome, among others.Senior-Løken syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated 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 mutated gene and 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 normal genes from both parents is 25%. The risk is the same for males and females.
|
Causes of Senior-Løken Syndrome. Senior-Løken syndrome is currently known to be caused by changes (pathogenic variants or mutations) in at least 10 genes: NPHP1, INVS /NPHP2, NPHP3, NPHP4, IQCB1/NPHP5, CEP290/NPHP6, SDCCAG8/NPHP10, WDR19/NPHP13, CEP164 and TRAF3IP1.The proteins encoded by these genes play a large role in cell structures called cilia. Cilia are microscopic hair-like structures that stick out from the surface of a cell and are responsible for transmitting information between cells. Cilia are essential for sensory input, since retinal photoreceptors have a cilium connecting outer and inner segments of the cell and there are also cilia in the developing inner ear but are also important for the structure and function of the cells in the kidneys.Variants in one of the above referred genes can lead to problems with the function of cilia, causing disruption of important signaling within cells. Therefore, the damaged cilia are responsible for Senior-Løken syndrome, which is considered as a “ciliopathy “, a heterogeneous group of genetic disorders which affect to 1% of all the rare disease patients and occur due to primary ciliary dysfunction, affecting many parts of the body, including the kidney, eye, liver and brain. However, it is still unclear how they specifically lead to Leber congenital amaurosis and nephronophthisis, and some overlapping between conditions caused by the large group of genes involved in ciliopathies can occur. Other ciliopathies are Bardet Biedl syndrome, Joubert syndrome, Laurence Moon syndrome, McKusick Kaufman syndrome, autosomal dominant and autosomal recessive polycystic kidney disease and Biemond syndrome, among others.Senior-Løken syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated 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 mutated gene and 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 normal genes from both parents is 25%. The risk is the same for males and females.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_3
|
Affects of Senior-Løken Syndrome
|
Senio-Løken syndrome is a very rare disorder affects males and females in equal numbers. It is estimated that the prevalence is 1/1 million people worldwide. Only a few families with the condition have been described in the medical literature.
|
Affects of Senior-Løken Syndrome. Senio-Løken syndrome is a very rare disorder affects males and females in equal numbers. It is estimated that the prevalence is 1/1 million people worldwide. Only a few families with the condition have been described in the medical literature.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_4
|
Related disorders of Senior-Løken Syndrome
|
Early onset retinal dystrophy is part of Senior-Løken syndrome, so symptoms can be similar to other non-syndromic retinal dystrophies.Leber congenital amaurosis is a retinal hereditary disorder of the eye. It is characterized by blindness at birth, roving eye movements, pressing and rubbing the eyes with a knuckle or finger (Franceschetti’s oculo-digital sign), pupils that react poorly to light and dilate widely in the dark. However, this disorder does not affect the kidneys. (For more information on this disorder, choose “Leber” as your search term in the Rare Disease Database.)Retinitis pigmentosa is one of a group of inherited retinal dystrophies causing degeneration of the retina. When the retina degenerates, the vision decreases from night blindness to tunnel vision, and vision usually leads to legal blindness. Retinitis pigmentosa may occur in association with other disorders such as deafness (Usher’s syndrome), central nervous system disorders, metabolic disorders, and chromosomal abnormalities. (For more information on this disorder, choose “Retinitis Pigmentosa” as your search term in the Rare Disease Database.).Nephronophthisis is also part of Senior-Løken syndrome, as well as other syndromes. Nephronophthisis is a rare disorder characterized by anemia, excessive urination (polyuria), excessive thirst (polydipsia) and toxic accumulation of the products of protein breakdown in the blood (uremia).Symptoms of the following disorders can be similar to those of Senior-Løken syndrome. Comparisons may be useful for a differential diagnosis:Juvenile nephronophthisis-medullary cystic disease is a diffuse kidney disease, either genetic or congenital in origin, which usually appears in children or young adults (juvenile nephronophthisis). It is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood (uremia) due to progressive failure of kidney function. (For more information on this disorder, choose “Medullary Cystic Disease” as your search term in the Rare Disease Database.)Polycystic kidney diseases are inherited disorders that are characterized by many cysts in both kidneys. This causes enlargement of the total kidney size, while reducing the functional kidney tissue by compression. (For more information on this disorder, choose “Polycystic Kidney Diseases” as your search term in the Rare Disease Database.)Rhyns syndrome is an extremely rare disorder characterized by retinitis pigmentosa, nephronophthisis, low functioning pituitary gland (hypopituitarism), skeletal abnormalities, drooping eyelids and liver disease. It is a recessive genetic disorder caused by variants in the TMEM67 gene.Mainzer-Saldino syndrome or Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a rare disorder characterized by chronic kidney failure, skeletal abnormalities of the hands, retinitis pigmentosa and muscular incoordination (ataxia). It is a recessive genetic disorder caused by variants in IFT140 gene.
|
Related disorders of Senior-Løken Syndrome. Early onset retinal dystrophy is part of Senior-Løken syndrome, so symptoms can be similar to other non-syndromic retinal dystrophies.Leber congenital amaurosis is a retinal hereditary disorder of the eye. It is characterized by blindness at birth, roving eye movements, pressing and rubbing the eyes with a knuckle or finger (Franceschetti’s oculo-digital sign), pupils that react poorly to light and dilate widely in the dark. However, this disorder does not affect the kidneys. (For more information on this disorder, choose “Leber” as your search term in the Rare Disease Database.)Retinitis pigmentosa is one of a group of inherited retinal dystrophies causing degeneration of the retina. When the retina degenerates, the vision decreases from night blindness to tunnel vision, and vision usually leads to legal blindness. Retinitis pigmentosa may occur in association with other disorders such as deafness (Usher’s syndrome), central nervous system disorders, metabolic disorders, and chromosomal abnormalities. (For more information on this disorder, choose “Retinitis Pigmentosa” as your search term in the Rare Disease Database.).Nephronophthisis is also part of Senior-Løken syndrome, as well as other syndromes. Nephronophthisis is a rare disorder characterized by anemia, excessive urination (polyuria), excessive thirst (polydipsia) and toxic accumulation of the products of protein breakdown in the blood (uremia).Symptoms of the following disorders can be similar to those of Senior-Løken syndrome. Comparisons may be useful for a differential diagnosis:Juvenile nephronophthisis-medullary cystic disease is a diffuse kidney disease, either genetic or congenital in origin, which usually appears in children or young adults (juvenile nephronophthisis). It is characterized by a gradual increase of urea and other by-products of protein breakdown in the blood (uremia) due to progressive failure of kidney function. (For more information on this disorder, choose “Medullary Cystic Disease” as your search term in the Rare Disease Database.)Polycystic kidney diseases are inherited disorders that are characterized by many cysts in both kidneys. This causes enlargement of the total kidney size, while reducing the functional kidney tissue by compression. (For more information on this disorder, choose “Polycystic Kidney Diseases” as your search term in the Rare Disease Database.)Rhyns syndrome is an extremely rare disorder characterized by retinitis pigmentosa, nephronophthisis, low functioning pituitary gland (hypopituitarism), skeletal abnormalities, drooping eyelids and liver disease. It is a recessive genetic disorder caused by variants in the TMEM67 gene.Mainzer-Saldino syndrome or Short-rib thoracic dysplasia (SRTD) with or without polydactyly is a rare disorder characterized by chronic kidney failure, skeletal abnormalities of the hands, retinitis pigmentosa and muscular incoordination (ataxia). It is a recessive genetic disorder caused by variants in IFT140 gene.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_5
|
Diagnosis of Senior-Løken Syndrome
|
Senior-Løken syndrome can be diagnosed through genetic testing and clinical examinations. A complete kidney and ophthalmologic evaluation should be performed, as well as hepatic and neurological exams. Genetic diagnosis will require testing for variants in the 10 genes; given that the most common variant is the deletion of NPHP1 gene, the genetic testing should include a method able to detect deletions in that gene.
|
Diagnosis of Senior-Løken Syndrome. Senior-Løken syndrome can be diagnosed through genetic testing and clinical examinations. A complete kidney and ophthalmologic evaluation should be performed, as well as hepatic and neurological exams. Genetic diagnosis will require testing for variants in the 10 genes; given that the most common variant is the deletion of NPHP1 gene, the genetic testing should include a method able to detect deletions in that gene.
| 1,103 |
Senior-Løken Syndrome
|
nord_1103_6
|
Therapies of Senior-Løken Syndrome
|
Children affected with Senior-Løken syndrome should be monitored regularly by a pediatric nephrologist. The child’s weight and height, kidney function, urinary concentration and blood pressure should be monitored. An early diagnosis of nephronophthisis can be managed and delay the progression of kidney failure; however, once end-stage kidney disease develops patients will require dialysis or a kidney transplant.Currently, there is no treatment to prevent the progression of vision loss.Patients with medullary cystic disease need careful management of uremia when it occurs. Diet must be carefully monitored. An increase of calories in the diet should be coupled with a reduction in the total content of dietary protein. Sufficient carbohydrates and fats should be consumed to provide energy and prevent the body from metabolizing its own proteins.When the retinal atrophy in Senior-Løken syndrome resembles retinitis pigmentosa, the patient may benefit from various visual aids. The aids may be 1) optical aids, such as Corning and NOIR glasses, the Fresnel Prising telescopes, microscopes and night vision aids; 2) non-optical aids, such as the wide-angle mobility light, paper guides, large print typewriters and adjustable stands; and 3) electronic aids such as Apollo Laser and Visualtek closed-circuit TV, reading machines and talking computers.Genetic counseling is recommended for patients and their families.
|
Therapies of Senior-Løken Syndrome. Children affected with Senior-Løken syndrome should be monitored regularly by a pediatric nephrologist. The child’s weight and height, kidney function, urinary concentration and blood pressure should be monitored. An early diagnosis of nephronophthisis can be managed and delay the progression of kidney failure; however, once end-stage kidney disease develops patients will require dialysis or a kidney transplant.Currently, there is no treatment to prevent the progression of vision loss.Patients with medullary cystic disease need careful management of uremia when it occurs. Diet must be carefully monitored. An increase of calories in the diet should be coupled with a reduction in the total content of dietary protein. Sufficient carbohydrates and fats should be consumed to provide energy and prevent the body from metabolizing its own proteins.When the retinal atrophy in Senior-Løken syndrome resembles retinitis pigmentosa, the patient may benefit from various visual aids. The aids may be 1) optical aids, such as Corning and NOIR glasses, the Fresnel Prising telescopes, microscopes and night vision aids; 2) non-optical aids, such as the wide-angle mobility light, paper guides, large print typewriters and adjustable stands; and 3) electronic aids such as Apollo Laser and Visualtek closed-circuit TV, reading machines and talking computers.Genetic counseling is recommended for patients and their families.
| 1,103 |
Senior-Løken Syndrome
|
nord_1104_0
|
Overview of Sennetsu Fever
|
Sennetsu Fever is a rare infectious disease belonging to a group of diseases known as the Human Ehrlichioses. These diseases are caused by bacteria belonging to the “Ehrlichia” family. Several forms of Human Ehrlichial infection have been identified including Sennetsu Fever, Human Monocytic Ehrlichiosis (HME), and Human Granulocytic Ehrlichiosis (HGE). Though caused by different strains of Ehrlichia bacteria, the disorders are all characterized by similar symptoms.The symptoms of Sennetsu Fever may include a sudden high fever, headache, and muscle aches (myalgia) within a few weeks after initial infection. In some cases, affected individuals may also experience nausea, vomiting, and/or loss of appetite (anorexia). In addition, in many cases, abnormal laboratory findings may include a decrease in white blood cells (leukopenia) and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Sennetsu Fever is caused by the bacterium Ehrlichia sennetsu. The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish.
|
Overview of Sennetsu Fever. Sennetsu Fever is a rare infectious disease belonging to a group of diseases known as the Human Ehrlichioses. These diseases are caused by bacteria belonging to the “Ehrlichia” family. Several forms of Human Ehrlichial infection have been identified including Sennetsu Fever, Human Monocytic Ehrlichiosis (HME), and Human Granulocytic Ehrlichiosis (HGE). Though caused by different strains of Ehrlichia bacteria, the disorders are all characterized by similar symptoms.The symptoms of Sennetsu Fever may include a sudden high fever, headache, and muscle aches (myalgia) within a few weeks after initial infection. In some cases, affected individuals may also experience nausea, vomiting, and/or loss of appetite (anorexia). In addition, in many cases, abnormal laboratory findings may include a decrease in white blood cells (leukopenia) and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Sennetsu Fever is caused by the bacterium Ehrlichia sennetsu. The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish.
| 1,104 |
Sennetsu Fever
|
nord_1104_1
|
Symptoms of Sennetsu Fever
|
The symptoms of Sennetsu Fever, the first recognized form of Human Ehrlichiosis, tend to begin approximately two weeks after an individual has been infected with the bacterium Ehrlichia sennetsu. Affected individuals may then experience severe headaches, muscle aches (myalgia), sudden fever, chills, swollen lymph nodes (lymphadenopathy), nausea, vomiting, and/or loss of appetite (anorexia). In very rare cases, a rash may appear on the skin.In the beginning of the illness, affected individuals may exhibit an abnormal decrease in the number of circulating white blood cells (leukopenia); later in the course of the infection, there may be an abnormal increase in the production of certain white blood cells (lymphocytosis) as the body's immune system works to fight the infection. Individuals with Sennetsu Fever may also exhibit an abnormally enlarged liver and spleen (hepatosplenomegaly) and a mild to moderate increase in the level of certain liver enzymes (hepatic transaminases).
|
Symptoms of Sennetsu Fever. The symptoms of Sennetsu Fever, the first recognized form of Human Ehrlichiosis, tend to begin approximately two weeks after an individual has been infected with the bacterium Ehrlichia sennetsu. Affected individuals may then experience severe headaches, muscle aches (myalgia), sudden fever, chills, swollen lymph nodes (lymphadenopathy), nausea, vomiting, and/or loss of appetite (anorexia). In very rare cases, a rash may appear on the skin.In the beginning of the illness, affected individuals may exhibit an abnormal decrease in the number of circulating white blood cells (leukopenia); later in the course of the infection, there may be an abnormal increase in the production of certain white blood cells (lymphocytosis) as the body's immune system works to fight the infection. Individuals with Sennetsu Fever may also exhibit an abnormally enlarged liver and spleen (hepatosplenomegaly) and a mild to moderate increase in the level of certain liver enzymes (hepatic transaminases).
| 1,104 |
Sennetsu Fever
|
nord_1104_2
|
Causes of Sennetsu Fever
|
The Human Ehrlichioses, including Sennetsu Fever, are caused by bacteria belonging to the “Ehrlichia” family. They are considered “gram-negative” bacteria. Bacteria may be classified as “gram negative” or “gram positive,” depending upon the results of “Gram's stain,” a testing method in which bacteria are stained with various solutions to help identify and classify the bacteria. Such staining may be essential in identifying a specific bacterium responsible for an infectious disorder and determining appropriate, effective treatments.Sennetsu Fever is caused by a bacterium called Ehrlichia sennetsu (or E. sennetsu). The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish. A vector is any organism that is infected with a particular disease agent (e.g., bacterium or virus), carries it, and later transmits it to another organism, which may then become infected by the disease agent in question. The genetic makeup of the bacterium E. sennetsu is closely related to that of a bacterium called Ehrlichia risticii, which causes an Ehrlichial infection in horses (Potomac Horse Fever).In Sennetsu Fever, the Ehrlichial bacterium (E. sennetsu) spreads through blood and lymphatic vessels. Lymph, a body fluid, carries cells that help fight infection. E. sennetsu then invades certain cells (monocytes and macrophages). These are large cells (mononuclear phagocytes) that play an essential role in the body's immune system by engulfing and digesting microorganisms (phagocytosis), such as bacteria and other foreign materials. The invading Ehrlichial bacteria grow within membrane-bound cavities (vacuoles) in monocytes and macrophages in the blood and certain body tissues (e.g., bone marrow, lymph nodes, liver, spleen, kidneys, lungs, and the fluid that surrounds the brain and spinal cord [cerebrospinal fluid]).
|
Causes of Sennetsu Fever. The Human Ehrlichioses, including Sennetsu Fever, are caused by bacteria belonging to the “Ehrlichia” family. They are considered “gram-negative” bacteria. Bacteria may be classified as “gram negative” or “gram positive,” depending upon the results of “Gram's stain,” a testing method in which bacteria are stained with various solutions to help identify and classify the bacteria. Such staining may be essential in identifying a specific bacterium responsible for an infectious disorder and determining appropriate, effective treatments.Sennetsu Fever is caused by a bacterium called Ehrlichia sennetsu (or E. sennetsu). The vector (or carrier) for this bacterium has not yet been determined; however, some researchers believe that infection may result from the ingestion of raw fish. A vector is any organism that is infected with a particular disease agent (e.g., bacterium or virus), carries it, and later transmits it to another organism, which may then become infected by the disease agent in question. The genetic makeup of the bacterium E. sennetsu is closely related to that of a bacterium called Ehrlichia risticii, which causes an Ehrlichial infection in horses (Potomac Horse Fever).In Sennetsu Fever, the Ehrlichial bacterium (E. sennetsu) spreads through blood and lymphatic vessels. Lymph, a body fluid, carries cells that help fight infection. E. sennetsu then invades certain cells (monocytes and macrophages). These are large cells (mononuclear phagocytes) that play an essential role in the body's immune system by engulfing and digesting microorganisms (phagocytosis), such as bacteria and other foreign materials. The invading Ehrlichial bacteria grow within membrane-bound cavities (vacuoles) in monocytes and macrophages in the blood and certain body tissues (e.g., bone marrow, lymph nodes, liver, spleen, kidneys, lungs, and the fluid that surrounds the brain and spinal cord [cerebrospinal fluid]).
| 1,104 |
Sennetsu Fever
|
nord_1104_3
|
Affects of Sennetsu Fever
|
The Ehrlichioses are a group of rare infectious diseases caused by members of the “Ehrlichia” bacteria family. Until recently, the Ehrlichioses were known primarily as veterinary disorders. Since the early 1900s, several forms of veterinary Ehrlichioses have been identified, each caused by a different strain of Ehrlichia; in most cases, the bacteria are transmitted by ticks (vectors). Veterinary Ehrlichial infections have been identified that cause disease in horses, sheep, deer, cattle, rodents, and/or dogs. For example, a form of Ehrlichial infection in dogs was first identified in Algeria in 1935 (Canine Ehrlichiosis). The disorder is now a well-recognized canine disease across the world; it is most common in subtropical and tropical areas. In rare cases, Ehrlichiosis may affect humans. The first recognized form of Human Ehrlichial infection, Sennetsu Fever, was identified in Japan in 1954. Reported cases of Sennetsu Fever appear to be limited to Western Japan and Malaysia. Researchers believe that the distinct geographic distributions of the Human Ehrlichioses may result from differences in the distribution of the various vectors (e.g., raw fish, Lone Star tick, American dog tick, deer tick) carrying and transmitting the different Ehrlichia bacterial strains.
|
Affects of Sennetsu Fever. The Ehrlichioses are a group of rare infectious diseases caused by members of the “Ehrlichia” bacteria family. Until recently, the Ehrlichioses were known primarily as veterinary disorders. Since the early 1900s, several forms of veterinary Ehrlichioses have been identified, each caused by a different strain of Ehrlichia; in most cases, the bacteria are transmitted by ticks (vectors). Veterinary Ehrlichial infections have been identified that cause disease in horses, sheep, deer, cattle, rodents, and/or dogs. For example, a form of Ehrlichial infection in dogs was first identified in Algeria in 1935 (Canine Ehrlichiosis). The disorder is now a well-recognized canine disease across the world; it is most common in subtropical and tropical areas. In rare cases, Ehrlichiosis may affect humans. The first recognized form of Human Ehrlichial infection, Sennetsu Fever, was identified in Japan in 1954. Reported cases of Sennetsu Fever appear to be limited to Western Japan and Malaysia. Researchers believe that the distinct geographic distributions of the Human Ehrlichioses may result from differences in the distribution of the various vectors (e.g., raw fish, Lone Star tick, American dog tick, deer tick) carrying and transmitting the different Ehrlichia bacterial strains.
| 1,104 |
Sennetsu Fever
|
nord_1104_4
|
Related disorders of Sennetsu Fever
|
Symptoms of the following disorders may be similar to those of Sennetsu Fever. Comparisons may be useful for a differential diagnosis: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). The invading bacteria grow within membrane-bound cavities (vacuoles) in the neutrophils in circulating blood. 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), and/or headaches. Some affected individuals may also experience coughing, nausea, vomiting, and/or confusion. In addition, in many cases, certain abnormal laboratory findings may occur including an increase in the level of certain liver enzymes (hepatic transaminases), low levels of circulating blood platelets (thrombocytopenia), anemia, and/or a decrease in certain white blood cells (granulocytopenia). In some severe cases, if Human Granulocytic Ehrlichiosis is left untreated, life-threatening symptoms, such as kidney failure and respiratory insufficiency, may result. 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.)Human Monocytic Ehrlichiosis (HME) is a rare infectious disease 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). In some cases, a rash may appear on the skin. 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. In many cases of HME, there is also an abnormal decrease in white blood cells (leukopenia), a low number of circulating blood platelets (thrombocytopenia), and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Some affected individuals may also exhibit inflammation of the liver (hepatitis). Most cases have occurred in the mid-Atlantic and southeastern states in the United States. (For more information on this disorder, choose “Human Monocytic Ehrlichiosis” as your search term in the Rare Disease Database.)The most recently identified form of Human Ehrlichiosis has been reported in four individuals in Missouri, all of whom experienced tick exposure several days prior to symptom onset. Based upon certain specialized laboratory tests, the four individuals tested positive for Ehrlichial infection yet negative for all known human forms of the disease. Further tests revealed that the infection was caused by Ehrlichia ewingii, a bacterium that was previously thought only to cause Ehrlichial infection in dogs (Canine Granulocytic Ehrlichiosis). The researchers indicated that there is no evidence of direct disease transmission from dogs to humans. Rather, humans and dogs both appear to be hosts to the same tick vectors. Associated symptoms typically include fever, headache, joint and muscle pain, and a general feeling of ill health (malaise). In addition, as with other forms of Human Ehrlichiosis, abnormal laboratory findings may also be present, such as abnormally low levels of circulating platelets (thrombocytopenia) and a decrease in white blood cells (leukopenia). Three of the four individuals with this form of Ehrlichiosis had been receiving therapy with medications that suppress the activities of the immune system (immunosuppressants). It is unclear whether infection with the E. ewingii bacterium usually does not affect individuals with sufficient immune system functioning (immunocompetence) or results in mild or no apparent symptoms (asymptomatic) in such cases. Therefore, the implications of such findings are not yet understood. All individuals with this form of Human Ehrlichiosis responded to treatment with the antibiotic doxycycline. (For more information on Human Ehrlichiosis treatment, please see the “Standard Therapies” section of this report below.)Lyme Disease is an infectious disorder 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 stiffness and pain of the large joints (infectious arthritis), especially 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 U.S. as well as other countries including China, Japan, Australia, and several countries in Europe. (For more information on this disorder, choose “Lyme” as your search term in the Rare Disease Database.)Babesiosis is a group of infectious diseases 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 (i.e., Babesia microti), and the deer tick (Ixodes dammini) is a known vector. Human Babesiosis infection may cause fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia). Additional features may include premature destruction of red blood cells (hemolytic anemia), an abnormal decrease in circulating blood platelets (thrombocytopenia) and white blood cells (leukopenia), and/or an enlarged spleen (splenomegaly). Symptoms may be mild in otherwise healthy people; some infected individuals may exhibit no symptoms (asymptomatic). A severe form of Babesiosis, which can be life-threatening if untreated, can occur in people who have had their spleens removed (splenectomized) or who have an impaired immune system. In the United States, Babesiosis is most common in the northeastern states. In rare cases, Babesiosis may occur in Europe. (For more information on this disorder, choose “Babesiosis” as your search term in the Rare Disease Database.)Rocky Mountain Spotted Fever is a rare infectious disorder caused by the bacterium Rickettsia rickettsii. The bacterium is carried and transmitted by tick vectors, such as the Lone Star tick (Amblyomma americanum) and the American dog tick (Dermacentor variabilis). Rocky Mountain Spotted Fever is characterized by severe headache, high fever, chills, muscle aches (myalgia), and/or confusion. In most cases, a skin rash may appear approximately two to six days after tick exposure; the rash may first appear on the palms, wrists, soles, ankles, and forearms, later spreading to the face, trunk, and lower arms and legs. Some affected individuals may also experience nausea, vomiting, and/or abdominal pain. In some cases, without early diagnosis and appropriate treatment, symptoms may become life-threatening. Rocky Mountain Spotted Fever characteristically occurs in outbreaks in various areas of the Midwestern, Eastern, and Southeastern United States. (For more information on this disorder, choose “Rocky Mountain Spotted Fever” as your search term in the Rare Disease Database.)Toxic Shock Syndrome is a rare infectious disorder caused by the bacterium Staphylococcus aureus, which produces and secretes a poison (toxin [enterotoxin F]). The initial symptoms of Toxic Shock Syndrome may include a sudden high fever, nausea, vomiting, diarrhea, headache, sore throat (pharyngitis), and/or a characteristic skin rash that resembles a bad sunburn. Later symptoms may include confusion, abnormally low blood pressure (hypotension), and/or abnormal liver function. Without early diagnosis and appropriate treatment, life-threatening symptoms may result. Most cases of Toxic Shock Syndrome occur in menstruating females, possibly in association with the prolonged use of high-absorbency tampons. However, some females who have not used tampons and some males have been affected by the disorder. (For more information on this disorder, choose “Toxic Shock” as your search term in the Rare Disease Database.)There are other infectious disorders that may be characterized by sudden high fever (febrile disorders), headache, myalgia, nausea, vomiting, thrombocytopenia, leukopenia, and/or other symptoms associated with Sennetsu Fever. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
|
Related disorders of Sennetsu Fever. Symptoms of the following disorders may be similar to those of Sennetsu Fever. Comparisons may be useful for a differential diagnosis: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). The invading bacteria grow within membrane-bound cavities (vacuoles) in the neutrophils in circulating blood. 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), and/or headaches. Some affected individuals may also experience coughing, nausea, vomiting, and/or confusion. In addition, in many cases, certain abnormal laboratory findings may occur including an increase in the level of certain liver enzymes (hepatic transaminases), low levels of circulating blood platelets (thrombocytopenia), anemia, and/or a decrease in certain white blood cells (granulocytopenia). In some severe cases, if Human Granulocytic Ehrlichiosis is left untreated, life-threatening symptoms, such as kidney failure and respiratory insufficiency, may result. 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.)Human Monocytic Ehrlichiosis (HME) is a rare infectious disease 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). In some cases, a rash may appear on the skin. 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. In many cases of HME, there is also an abnormal decrease in white blood cells (leukopenia), a low number of circulating blood platelets (thrombocytopenia), and/or an abnormal increase in the level of certain liver enzymes (hepatic transaminases). Some affected individuals may also exhibit inflammation of the liver (hepatitis). Most cases have occurred in the mid-Atlantic and southeastern states in the United States. (For more information on this disorder, choose “Human Monocytic Ehrlichiosis” as your search term in the Rare Disease Database.)The most recently identified form of Human Ehrlichiosis has been reported in four individuals in Missouri, all of whom experienced tick exposure several days prior to symptom onset. Based upon certain specialized laboratory tests, the four individuals tested positive for Ehrlichial infection yet negative for all known human forms of the disease. Further tests revealed that the infection was caused by Ehrlichia ewingii, a bacterium that was previously thought only to cause Ehrlichial infection in dogs (Canine Granulocytic Ehrlichiosis). The researchers indicated that there is no evidence of direct disease transmission from dogs to humans. Rather, humans and dogs both appear to be hosts to the same tick vectors. Associated symptoms typically include fever, headache, joint and muscle pain, and a general feeling of ill health (malaise). In addition, as with other forms of Human Ehrlichiosis, abnormal laboratory findings may also be present, such as abnormally low levels of circulating platelets (thrombocytopenia) and a decrease in white blood cells (leukopenia). Three of the four individuals with this form of Ehrlichiosis had been receiving therapy with medications that suppress the activities of the immune system (immunosuppressants). It is unclear whether infection with the E. ewingii bacterium usually does not affect individuals with sufficient immune system functioning (immunocompetence) or results in mild or no apparent symptoms (asymptomatic) in such cases. Therefore, the implications of such findings are not yet understood. All individuals with this form of Human Ehrlichiosis responded to treatment with the antibiotic doxycycline. (For more information on Human Ehrlichiosis treatment, please see the “Standard Therapies” section of this report below.)Lyme Disease is an infectious disorder 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 stiffness and pain of the large joints (infectious arthritis), especially 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 U.S. as well as other countries including China, Japan, Australia, and several countries in Europe. (For more information on this disorder, choose “Lyme” as your search term in the Rare Disease Database.)Babesiosis is a group of infectious diseases 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 (i.e., Babesia microti), and the deer tick (Ixodes dammini) is a known vector. Human Babesiosis infection may cause fever, chills, headache, nausea, vomiting, and/or muscle aches (myalgia). Additional features may include premature destruction of red blood cells (hemolytic anemia), an abnormal decrease in circulating blood platelets (thrombocytopenia) and white blood cells (leukopenia), and/or an enlarged spleen (splenomegaly). Symptoms may be mild in otherwise healthy people; some infected individuals may exhibit no symptoms (asymptomatic). A severe form of Babesiosis, which can be life-threatening if untreated, can occur in people who have had their spleens removed (splenectomized) or who have an impaired immune system. In the United States, Babesiosis is most common in the northeastern states. In rare cases, Babesiosis may occur in Europe. (For more information on this disorder, choose “Babesiosis” as your search term in the Rare Disease Database.)Rocky Mountain Spotted Fever is a rare infectious disorder caused by the bacterium Rickettsia rickettsii. The bacterium is carried and transmitted by tick vectors, such as the Lone Star tick (Amblyomma americanum) and the American dog tick (Dermacentor variabilis). Rocky Mountain Spotted Fever is characterized by severe headache, high fever, chills, muscle aches (myalgia), and/or confusion. In most cases, a skin rash may appear approximately two to six days after tick exposure; the rash may first appear on the palms, wrists, soles, ankles, and forearms, later spreading to the face, trunk, and lower arms and legs. Some affected individuals may also experience nausea, vomiting, and/or abdominal pain. In some cases, without early diagnosis and appropriate treatment, symptoms may become life-threatening. Rocky Mountain Spotted Fever characteristically occurs in outbreaks in various areas of the Midwestern, Eastern, and Southeastern United States. (For more information on this disorder, choose “Rocky Mountain Spotted Fever” as your search term in the Rare Disease Database.)Toxic Shock Syndrome is a rare infectious disorder caused by the bacterium Staphylococcus aureus, which produces and secretes a poison (toxin [enterotoxin F]). The initial symptoms of Toxic Shock Syndrome may include a sudden high fever, nausea, vomiting, diarrhea, headache, sore throat (pharyngitis), and/or a characteristic skin rash that resembles a bad sunburn. Later symptoms may include confusion, abnormally low blood pressure (hypotension), and/or abnormal liver function. Without early diagnosis and appropriate treatment, life-threatening symptoms may result. Most cases of Toxic Shock Syndrome occur in menstruating females, possibly in association with the prolonged use of high-absorbency tampons. However, some females who have not used tampons and some males have been affected by the disorder. (For more information on this disorder, choose “Toxic Shock” as your search term in the Rare Disease Database.)There are other infectious disorders that may be characterized by sudden high fever (febrile disorders), headache, myalgia, nausea, vomiting, thrombocytopenia, leukopenia, and/or other symptoms associated with Sennetsu Fever. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
| 1,104 |
Sennetsu Fever
|
nord_1104_5
|
Diagnosis of Sennetsu Fever
|
Diagnosis of Sennetsu Fever.
| 1,104 |
Sennetsu Fever
|
|
nord_1104_6
|
Therapies of Sennetsu Fever
|
Sennetsu Fever may be diagnosed based upon a thorough clinical evaluation, characteristic findings, and specialized laboratory tests. Blood tests may reveal findings often associated with the Human Ehrlichioses such as abnormally low levels of circulating blood platelets (thrombocytopenia), low levels of certain white blood cells (leukopenia), and/or elevated levels of certain liver enzymes (such as aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). In some cases, laboratory tests may reveal abnormalities of the cerebrospinal fluid; chest X-rays may reveal abnormalities in the lungs (pulmonary infiltrates).Specialized laboratory tests may include Indirect Immunofluorescence Assays (IFA) conducted on the fluid portion of an affected individual's blood (serum). Antibodies, which are proteins manufactured by certain white blood cells, help the body fight toxins and invading microorganisms. In Indirect Immunofluorescence Assays, human antibodies are marked with special fluorescent dyes and a microscope with ultraviolet light is used, enabling researchers to observe antibody response to certain microorganisms. IFA testing has been used in confirming a diagnosis of all known types of Human Ehrlichial infection. Sennetsu Fever may be diagnosed by observing the antibody response in a patient's blood serum to the bacterium Ehrlichia sennetsu.Measurable, diagnostic rises in antibody response to the Ehrlichia sennetsu bacteria may not occur until several weeks after the onset of Sennetsu Fever. As a result, initial IFA blood serum results may be negative in some cases. Therefore, more sensitive testing techniques that can help establish early diagnosis may be used in some cases.Information in the medical literature indicates that because it may be difficult to differentiate Human Ehrlichial infection, such as Sennetsu Fever, from other illnesses that are also characterized by high fever (febrile illnesses), Ehrlichiosis should be considered in any patient with high fever, thrombocytopenia, and leukopenia who has recently been exposed to known vectors for Ehrlichial infection. If Sennetsu Fever is suspected, treatment should not be delayed until diagnosis has been confirmed by IFA testing, since a positive antibody response may not occur until several weeks after initial infection. Therapy should begin as soon as possible after the onset of symptoms.The treatment of Sennetsu Fever usually entails standard doses of tetracycline antibiotics. The antibiotic drugs doxycycline or minocycline have also been administered to treat this disease. In severe cases of Sennetsu Fever, hospitalization may be required. Other treatment is symptomatic and supportive.
|
Therapies of Sennetsu Fever. Sennetsu Fever may be diagnosed based upon a thorough clinical evaluation, characteristic findings, and specialized laboratory tests. Blood tests may reveal findings often associated with the Human Ehrlichioses such as abnormally low levels of circulating blood platelets (thrombocytopenia), low levels of certain white blood cells (leukopenia), and/or elevated levels of certain liver enzymes (such as aspartate aminotransferase [AST] and alanine aminotransferase [ALT]). In some cases, laboratory tests may reveal abnormalities of the cerebrospinal fluid; chest X-rays may reveal abnormalities in the lungs (pulmonary infiltrates).Specialized laboratory tests may include Indirect Immunofluorescence Assays (IFA) conducted on the fluid portion of an affected individual's blood (serum). Antibodies, which are proteins manufactured by certain white blood cells, help the body fight toxins and invading microorganisms. In Indirect Immunofluorescence Assays, human antibodies are marked with special fluorescent dyes and a microscope with ultraviolet light is used, enabling researchers to observe antibody response to certain microorganisms. IFA testing has been used in confirming a diagnosis of all known types of Human Ehrlichial infection. Sennetsu Fever may be diagnosed by observing the antibody response in a patient's blood serum to the bacterium Ehrlichia sennetsu.Measurable, diagnostic rises in antibody response to the Ehrlichia sennetsu bacteria may not occur until several weeks after the onset of Sennetsu Fever. As a result, initial IFA blood serum results may be negative in some cases. Therefore, more sensitive testing techniques that can help establish early diagnosis may be used in some cases.Information in the medical literature indicates that because it may be difficult to differentiate Human Ehrlichial infection, such as Sennetsu Fever, from other illnesses that are also characterized by high fever (febrile illnesses), Ehrlichiosis should be considered in any patient with high fever, thrombocytopenia, and leukopenia who has recently been exposed to known vectors for Ehrlichial infection. If Sennetsu Fever is suspected, treatment should not be delayed until diagnosis has been confirmed by IFA testing, since a positive antibody response may not occur until several weeks after initial infection. Therapy should begin as soon as possible after the onset of symptoms.The treatment of Sennetsu Fever usually entails standard doses of tetracycline antibiotics. The antibiotic drugs doxycycline or minocycline have also been administered to treat this disease. In severe cases of Sennetsu Fever, hospitalization may be required. Other treatment is symptomatic and supportive.
| 1,104 |
Sennetsu Fever
|
nord_1105_0
|
Overview of Sepiapterin Reductase Deficiency
|
SummarySepiapterin reductase deficiency (SRD) is a rare genetic disorder that is characterized by abnormally low levels of certain neurotransmitters. Neurotransmitters are chemicals that modify, amplify or transmit nerve impulses from one nerve cell to another, enabling nerve cells to communicate. The severity of sepiapterin reductase deficiency can range from a mild movement disorder at one end to severe, progressive neurological disease at the other. Common symptoms include lack of muscle tone (hypotonia), drooling, loss of coordination, abnormal movements, delayed motor and language development (i.e. delays in reaching developmental milestones), and/or dystonia. Dystonia is a general term for a group of muscle disorders, generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). The specific symptoms can vary dramatically from one person to another. Prompt diagnosis and treatment can reduce or potentially prevent severe, irreversible neurological damage. Children with sepiapterin reductase deficiency may show a dramatic response and sustained improvement when treated with levodopa. Levodopa is a chemical that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Some individuals show benefit with treatment with addition of 5-HTP, a neurotransmitter precursor that is converted to serotonin. Sepiapterin reductase deficiency is caused by mutations in the SPR gene and is inherited as an autosomal recessive disorder.IntroductionSepiapterin reductase deficiency can be classified as a form of dystonia, a pediatric neurotransmitter disorder or a disorder of tetrahydrobiopterin deficiency. The disorder is sometimes referred to as a form of dopa-responsive dystonia. However, dystonia is not always present in infancy and may not be a universal symptom so that term may not apply to all cases. The non-specific symptoms of this condition may be misdiagnosed as cerebral palsy.
|
Overview of Sepiapterin Reductase Deficiency. SummarySepiapterin reductase deficiency (SRD) is a rare genetic disorder that is characterized by abnormally low levels of certain neurotransmitters. Neurotransmitters are chemicals that modify, amplify or transmit nerve impulses from one nerve cell to another, enabling nerve cells to communicate. The severity of sepiapterin reductase deficiency can range from a mild movement disorder at one end to severe, progressive neurological disease at the other. Common symptoms include lack of muscle tone (hypotonia), drooling, loss of coordination, abnormal movements, delayed motor and language development (i.e. delays in reaching developmental milestones), and/or dystonia. Dystonia is a general term for a group of muscle disorders, generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). The specific symptoms can vary dramatically from one person to another. Prompt diagnosis and treatment can reduce or potentially prevent severe, irreversible neurological damage. Children with sepiapterin reductase deficiency may show a dramatic response and sustained improvement when treated with levodopa. Levodopa is a chemical that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Some individuals show benefit with treatment with addition of 5-HTP, a neurotransmitter precursor that is converted to serotonin. Sepiapterin reductase deficiency is caused by mutations in the SPR gene and is inherited as an autosomal recessive disorder.IntroductionSepiapterin reductase deficiency can be classified as a form of dystonia, a pediatric neurotransmitter disorder or a disorder of tetrahydrobiopterin deficiency. The disorder is sometimes referred to as a form of dopa-responsive dystonia. However, dystonia is not always present in infancy and may not be a universal symptom so that term may not apply to all cases. The non-specific symptoms of this condition may be misdiagnosed as cerebral palsy.
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_1
|
Symptoms of Sepiapterin Reductase Deficiency
|
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about sepiapterin reductase deficiency is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.The specific symptoms and severity associated with sepiapterin reductase deficiency can vary greatly from one person to another. Some individuals develop severe, disabling motor and cognitive deficits; others only experience mild symptoms that can go unnoticed, and may only be diagnosed after the disorder is identified in a more severely affected family member. Prompt diagnosis and early treatment of sepiapterin reductase deficiency is essential to reduce or potentially prevent progressive neurological damage.Symptoms usually become apparent within the first year of life. Some infants may exhibit microcephaly, a condition defined as having a head circumference smaller than normally would be expected based on age and gender. Common symptoms include dystonia, delays in attaining developmental milestones (developmental delays) including delays in motor and speech development, reduced muscle tone (axial hypotonia), and abnormal movements of the eyes that can range from brief upward rolling of the eyes to oculogyric crises, in which the eyes roll upward for a sustained period of time.In some cases, certain symptoms may become noticeably worse or more pronounced in the afternoon and evening than in the morning (diurnal fluctuation). Dystonia is not always present during infancy and may develop later in childhood. Some individuals may not develop dystonia or only experience mild dystonia that can go unnoticed in infancy. Generally, the most common symptoms in infancy are nonspecific and can occur in many different neurological disorders, making it difficult to obtain a proper diagnosis.Some affected children develop intellectual disability while others develop mild or moderate learning disabilities. Sleep disturbances particularly excessive daytime sleepiness (hypersomnia), drooling, and psychological symptoms including anxiety, irritability, and hyperactivity may also occur.Exaggerated reflexes (hyperreflexia) and excess muscle tone of the arms and legs so that they may be stiff and difficult to move (limb hypertonia) are also relatively common findings. Less common symptoms include difficulty speaking (dysarthria), abnormal tongue movements, and abnormalities of the autonomic nervous system. The autonomic nervous system controls involuntary or automatic body processes. Excessive sweating would be an example of an autonomic sign of the disorder.Some individuals develop symptoms that resemble those seen in Parkinson’s disease, which is sometimes referred to as parkinsonism. These symptoms include tremors, abnormal slowness of movement (bradykinesia), muscle stiffness or rigidity, and an inability to use facial muscles to express emotions (masked facies).
|
Symptoms of Sepiapterin Reductase Deficiency. Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about sepiapterin reductase deficiency is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.The specific symptoms and severity associated with sepiapterin reductase deficiency can vary greatly from one person to another. Some individuals develop severe, disabling motor and cognitive deficits; others only experience mild symptoms that can go unnoticed, and may only be diagnosed after the disorder is identified in a more severely affected family member. Prompt diagnosis and early treatment of sepiapterin reductase deficiency is essential to reduce or potentially prevent progressive neurological damage.Symptoms usually become apparent within the first year of life. Some infants may exhibit microcephaly, a condition defined as having a head circumference smaller than normally would be expected based on age and gender. Common symptoms include dystonia, delays in attaining developmental milestones (developmental delays) including delays in motor and speech development, reduced muscle tone (axial hypotonia), and abnormal movements of the eyes that can range from brief upward rolling of the eyes to oculogyric crises, in which the eyes roll upward for a sustained period of time.In some cases, certain symptoms may become noticeably worse or more pronounced in the afternoon and evening than in the morning (diurnal fluctuation). Dystonia is not always present during infancy and may develop later in childhood. Some individuals may not develop dystonia or only experience mild dystonia that can go unnoticed in infancy. Generally, the most common symptoms in infancy are nonspecific and can occur in many different neurological disorders, making it difficult to obtain a proper diagnosis.Some affected children develop intellectual disability while others develop mild or moderate learning disabilities. Sleep disturbances particularly excessive daytime sleepiness (hypersomnia), drooling, and psychological symptoms including anxiety, irritability, and hyperactivity may also occur.Exaggerated reflexes (hyperreflexia) and excess muscle tone of the arms and legs so that they may be stiff and difficult to move (limb hypertonia) are also relatively common findings. Less common symptoms include difficulty speaking (dysarthria), abnormal tongue movements, and abnormalities of the autonomic nervous system. The autonomic nervous system controls involuntary or automatic body processes. Excessive sweating would be an example of an autonomic sign of the disorder.Some individuals develop symptoms that resemble those seen in Parkinson’s disease, which is sometimes referred to as parkinsonism. These symptoms include tremors, abnormal slowness of movement (bradykinesia), muscle stiffness or rigidity, and an inability to use facial muscles to express emotions (masked facies).
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_2
|
Causes of Sepiapterin Reductase Deficiency
|
Sepiapterin reductase deficiency is caused by mutations in the SPR gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.Investigators have determined that the SPR gene is located on the short arm (p) of chromosome 2 (2p13.2). 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 2p13.2” refers to band 13.2 on the short arm of chromosome 2.In most cases, mutations in the SPR gene are inherited as autosomal recessive traits. Recessive genetic disorders occur when an individual inherits an abnormality in the same gene 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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.The SPR gene contains instructions for creating (encoding) the enzyme sepiapterin reductase, which is the third (and last) enzyme required for the creation (synthesis) of tetrahydrobiopterin. Mutations in the SPR gene results in deficient levels of functional sepiapterin reductase enzyme and, consequently, improper or deficient production of tetrahydrobiopterin, a naturally-occurring compound that acts as a cofactor. A cofactor is a non-protein substance in the body that enhances or is necessary for the proper function of certain enzymes. When tetrahydrobiopterin is deficient, the chemical balance within the body is upset. Tetrahydrobiopterin has several functions within the body including assisting in the breaking down or processing certain amino acids. Tetrahydrobiopterin is also necessary for the proper development of amine neurotransmitters such as catecholamines (i.e. dopamine, norepinephrine, or epinephrine) and serotonin. Catecholamines are essential for the proper function of certain processes of the brain especially those that control movement. Serotonin helps to regulate mood, appetite, memory, sleep cycles, and certain muscular function.
|
Causes of Sepiapterin Reductase Deficiency. Sepiapterin reductase deficiency is caused by mutations in the SPR gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.Investigators have determined that the SPR gene is located on the short arm (p) of chromosome 2 (2p13.2). 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 2p13.2” refers to band 13.2 on the short arm of chromosome 2.In most cases, mutations in the SPR gene are inherited as autosomal recessive traits. Recessive genetic disorders occur when an individual inherits an abnormality in the same gene 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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.The SPR gene contains instructions for creating (encoding) the enzyme sepiapterin reductase, which is the third (and last) enzyme required for the creation (synthesis) of tetrahydrobiopterin. Mutations in the SPR gene results in deficient levels of functional sepiapterin reductase enzyme and, consequently, improper or deficient production of tetrahydrobiopterin, a naturally-occurring compound that acts as a cofactor. A cofactor is a non-protein substance in the body that enhances or is necessary for the proper function of certain enzymes. When tetrahydrobiopterin is deficient, the chemical balance within the body is upset. Tetrahydrobiopterin has several functions within the body including assisting in the breaking down or processing certain amino acids. Tetrahydrobiopterin is also necessary for the proper development of amine neurotransmitters such as catecholamines (i.e. dopamine, norepinephrine, or epinephrine) and serotonin. Catecholamines are essential for the proper function of certain processes of the brain especially those that control movement. Serotonin helps to regulate mood, appetite, memory, sleep cycles, and certain muscular function.
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_3
|
Affects of Sepiapterin Reductase Deficiency
|
Sepiapterin reductase deficiency is an extremely rare disorder that affects males and females in equal numbers. More than 40 cases have been described in the medical literature. The exact incidence or prevalence is unknown. Because cases can go undiagnosed or misdiagnosed, determining the true frequency of the disorder in the general population is difficult.
|
Affects of Sepiapterin Reductase Deficiency. Sepiapterin reductase deficiency is an extremely rare disorder that affects males and females in equal numbers. More than 40 cases have been described in the medical literature. The exact incidence or prevalence is unknown. Because cases can go undiagnosed or misdiagnosed, determining the true frequency of the disorder in the general population is difficult.
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_4
|
Related disorders of Sepiapterin Reductase Deficiency
|
Symptoms of the following disorders can be similar to those of sepiapterin reductase deficiency. Comparisons may be useful for a differential diagnosis.Segawa syndrome is a rare genetic disorder characterized by an uncoordinated or clumsy manner of walking (abnormal gait) and dystonia. Dystonia is a general term for a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). Dystonia in Segawa syndrome usually affects the legs, but some children may first develop dystonia in the arms. In some cases, usually in adolescents and adults, the symptoms of Segawa syndrome may become noticeably worse or more pronounced in the afternoon and evening than in the morning (diurnal fluctuation). The symptoms of Segawa syndrome usually become apparent by around six years of age. Intelligence is not affected. Children with Segawa syndrome usually show a dramatic and sustained improvement when treated with levodopa. Levodopa is an amino acid that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Dopamine is deficient in children with Segawa syndrome. The disorder is caused by mutations of the GCH1 gene. The GCH1 gene mutation is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Segawa” as your search term in the Rare Disease Database.)There are additional metabolic disorders that have been identified in which certain enzyme deficiencies result in disrupted metabolism of a neurotransmitter or neurotransmitters. These disorders include tyrosine hydroxylase deficiency, aromatic L-amino acid decarboxylase deficiency, succinic semialdehyde dehydrogenase (SSADH), and disorders of tetrahydrobiopterin deficiency. Although associated neurological and neuromuscular symptoms may vary, these disorders may have certain features that are similar to those associated with sepiapterin reductase deficiency. Such abnormalities may include abnormally low muscle tone (hypotonia), delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), limb dystonia, irritability, abnormal eye movements, and/or other symptoms and findings. Evidence suggests that there may be other currently unidentified metabolic disorders resulting in disrupted metabolism of neurotransmitters. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Cerebral palsy is a general term that covers a group of disorders that involve impairment of muscle control or coordination resulting from injury to the brain during its early stages of development (the fetal, perinatal or early childhood stages). There may be problems associated with involuntary movements, vision, hearing, communication skills, perception levels, intellect and seizures. Individuals with cerebral palsy often experience delays in reaching developmental milestones. The specific symptoms associated with cerebral palsy vary greatly from case to case. (For more information on this disorder, choose “cerebral palsy” as your search term in the Rare Disease Database.)
|
Related disorders of Sepiapterin Reductase Deficiency. Symptoms of the following disorders can be similar to those of sepiapterin reductase deficiency. Comparisons may be useful for a differential diagnosis.Segawa syndrome is a rare genetic disorder characterized by an uncoordinated or clumsy manner of walking (abnormal gait) and dystonia. Dystonia is a general term for a group of muscle disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures). Dystonia in Segawa syndrome usually affects the legs, but some children may first develop dystonia in the arms. In some cases, usually in adolescents and adults, the symptoms of Segawa syndrome may become noticeably worse or more pronounced in the afternoon and evening than in the morning (diurnal fluctuation). The symptoms of Segawa syndrome usually become apparent by around six years of age. Intelligence is not affected. Children with Segawa syndrome usually show a dramatic and sustained improvement when treated with levodopa. Levodopa is an amino acid that is converted to dopamine, a brain chemical that serves as a neurotransmitter. Dopamine is deficient in children with Segawa syndrome. The disorder is caused by mutations of the GCH1 gene. The GCH1 gene mutation is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Segawa” as your search term in the Rare Disease Database.)There are additional metabolic disorders that have been identified in which certain enzyme deficiencies result in disrupted metabolism of a neurotransmitter or neurotransmitters. These disorders include tyrosine hydroxylase deficiency, aromatic L-amino acid decarboxylase deficiency, succinic semialdehyde dehydrogenase (SSADH), and disorders of tetrahydrobiopterin deficiency. Although associated neurological and neuromuscular symptoms may vary, these disorders may have certain features that are similar to those associated with sepiapterin reductase deficiency. Such abnormalities may include abnormally low muscle tone (hypotonia), delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), limb dystonia, irritability, abnormal eye movements, and/or other symptoms and findings. Evidence suggests that there may be other currently unidentified metabolic disorders resulting in disrupted metabolism of neurotransmitters. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Cerebral palsy is a general term that covers a group of disorders that involve impairment of muscle control or coordination resulting from injury to the brain during its early stages of development (the fetal, perinatal or early childhood stages). There may be problems associated with involuntary movements, vision, hearing, communication skills, perception levels, intellect and seizures. Individuals with cerebral palsy often experience delays in reaching developmental milestones. The specific symptoms associated with cerebral palsy vary greatly from case to case. (For more information on this disorder, choose “cerebral palsy” as your search term in the Rare Disease Database.)
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_5
|
Diagnosis of Sepiapterin Reductase Deficiency
|
A diagnosis of sepiapterin reductase deficiency is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Unlike other disorders of tetrahydrobiopterin deficiency, sepiapterin reductase deficiency is not associated with elevated phenylalanine levels and, consequently, will not be detected upon newborn screening.Clinical Testing and WorkupA diagnosis may be made after the evaluation of cerebrospinal fluid (CSF), which can demonstrate low levels byproducts (metabolites) of the breakdown (metabolism) of neurotransmitter such as 5-hydroxyindoleacetic (5-HIAA) and homovanilic acid (HVA). In individuals with sepiapterin reductase deficiency, CSF study will also demonstrate elevated levels of biopterin and dihydrobiopterin, which are pterins. Pterins are the byproducts of the metabolism of tetrahydrobiopterin.Another rarely used test that can indicate the disorder is an enzyme assay, which is a test that can demonstrate low activity of the sepiapterin reductase enzyme in specialized cells known as fibroblasts.Molecular genetic testing can confirm a diagnosis. Molecular genetic testing can detect mutations in the SPR gene known to cause sepiapterin reductase deficiency, but is available only as a diagnostic service at specialized laboratories.
|
Diagnosis of Sepiapterin Reductase Deficiency. A diagnosis of sepiapterin reductase deficiency is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Unlike other disorders of tetrahydrobiopterin deficiency, sepiapterin reductase deficiency is not associated with elevated phenylalanine levels and, consequently, will not be detected upon newborn screening.Clinical Testing and WorkupA diagnosis may be made after the evaluation of cerebrospinal fluid (CSF), which can demonstrate low levels byproducts (metabolites) of the breakdown (metabolism) of neurotransmitter such as 5-hydroxyindoleacetic (5-HIAA) and homovanilic acid (HVA). In individuals with sepiapterin reductase deficiency, CSF study will also demonstrate elevated levels of biopterin and dihydrobiopterin, which are pterins. Pterins are the byproducts of the metabolism of tetrahydrobiopterin.Another rarely used test that can indicate the disorder is an enzyme assay, which is a test that can demonstrate low activity of the sepiapterin reductase enzyme in specialized cells known as fibroblasts.Molecular genetic testing can confirm a diagnosis. Molecular genetic testing can detect mutations in the SPR gene known to cause sepiapterin reductase deficiency, but is available only as a diagnostic service at specialized laboratories.
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1105_6
|
Therapies of Sepiapterin Reductase Deficiency
|
TreatmentPrompt recognition and early treatment of sepiapterin reductase deficiency is critical in reducing or preventing the potentially severe, irreversible neurologic damage that can occur in severe cases. The focus of treatment is to restore the proper balance of neurotransmitters in the brain. Affected individuals are initially treated with low levels of a chemical or neurotransmitter precursor called levodopa (L-dopa) that is converted to the neurotransmitter, dopamine, by enzymes in the liver and brain. Dopamine cannot cross the blood-brain barrier, so affected individuals also receive a second medication (usually carbidopa) to prevent conversion of L-dopa to dopamine before it can cross the blood-brain barrier. The blood-brain barrier is a protective network of blood vessels and cells that allow some materials to enter the brain, while keeping other materials out.The response to L-dopa therapy varies among affected individuals. Some people respond quickly and completely to L-dopa therapy seeing a significant improvement of symptoms. In others, the response may take time and improvement is seen gradually over a few months. L-dopa is particularly effective in treatment of movement disorders associated with sepiapterin reductase deficiency, with symptomatic improvement occurring within hours of treatment in some cases. The impact on cognitive issues is less consistent. In some cases, the dosage of L-dopa used to treat an affected individual may need to be adjusted until a dosage can be achieved that effectively treats the disorder. In individuals who do not respond to this therapy, another neurotransmitter precursor such as 5-hydroxytryptophan may be added to the treatment regimen (combination therapy). In most cases, supplemental therapy with neurotransmitter precursors is required for life.Some individuals may develop a side effect of L-dopa therapy called dyskinesia, which refers to abnormal involuntary movements when performing voluntary movements (dyskinesia). Dyskinesia goes away if the dose of L-dopa is lowered; when the dose is gradually increased later on, dyskinesia usually does not reappear.Genetic counseling may be of benefit for affected individuals and their families. Psychosocial support for the entire family is essential as well.
|
Therapies of Sepiapterin Reductase Deficiency. TreatmentPrompt recognition and early treatment of sepiapterin reductase deficiency is critical in reducing or preventing the potentially severe, irreversible neurologic damage that can occur in severe cases. The focus of treatment is to restore the proper balance of neurotransmitters in the brain. Affected individuals are initially treated with low levels of a chemical or neurotransmitter precursor called levodopa (L-dopa) that is converted to the neurotransmitter, dopamine, by enzymes in the liver and brain. Dopamine cannot cross the blood-brain barrier, so affected individuals also receive a second medication (usually carbidopa) to prevent conversion of L-dopa to dopamine before it can cross the blood-brain barrier. The blood-brain barrier is a protective network of blood vessels and cells that allow some materials to enter the brain, while keeping other materials out.The response to L-dopa therapy varies among affected individuals. Some people respond quickly and completely to L-dopa therapy seeing a significant improvement of symptoms. In others, the response may take time and improvement is seen gradually over a few months. L-dopa is particularly effective in treatment of movement disorders associated with sepiapterin reductase deficiency, with symptomatic improvement occurring within hours of treatment in some cases. The impact on cognitive issues is less consistent. In some cases, the dosage of L-dopa used to treat an affected individual may need to be adjusted until a dosage can be achieved that effectively treats the disorder. In individuals who do not respond to this therapy, another neurotransmitter precursor such as 5-hydroxytryptophan may be added to the treatment regimen (combination therapy). In most cases, supplemental therapy with neurotransmitter precursors is required for life.Some individuals may develop a side effect of L-dopa therapy called dyskinesia, which refers to abnormal involuntary movements when performing voluntary movements (dyskinesia). Dyskinesia goes away if the dose of L-dopa is lowered; when the dose is gradually increased later on, dyskinesia usually does not reappear.Genetic counseling may be of benefit for affected individuals and their families. Psychosocial support for the entire family is essential as well.
| 1,105 |
Sepiapterin Reductase Deficiency
|
nord_1106_0
|
Overview of SETBP1 Haploinsufficiency Disorder
|
SETBP1 haploinsufficiency disorder (SETBP1-HD) is an extremely rare genetic neurodevelopmental disorder in which there is a variation (mutation) in the SETBP1 gene. Variations in the SETBP1 gene can potentially cause a variety of signs and symptoms; how the disorder affects one child can be very different from how it affects another. Neurodevelopmental disorders are ones that impair or alter the growth and development of the brain and the central nervous system. Common symptoms include varying degrees of intellectual disability, delays in reaching developmental milestones (developmental delays), delays or difficulty in being able to speak (speech delays) and distinctive facial features. In most instances, variations in the SETBP1 gene occur spontaneously and there is no family history of the disorder (de novo variations). Treatment is based on the specific symptoms present in each individual.
|
Overview of SETBP1 Haploinsufficiency Disorder. SETBP1 haploinsufficiency disorder (SETBP1-HD) is an extremely rare genetic neurodevelopmental disorder in which there is a variation (mutation) in the SETBP1 gene. Variations in the SETBP1 gene can potentially cause a variety of signs and symptoms; how the disorder affects one child can be very different from how it affects another. Neurodevelopmental disorders are ones that impair or alter the growth and development of the brain and the central nervous system. Common symptoms include varying degrees of intellectual disability, delays in reaching developmental milestones (developmental delays), delays or difficulty in being able to speak (speech delays) and distinctive facial features. In most instances, variations in the SETBP1 gene occur spontaneously and there is no family history of the disorder (de novo variations). Treatment is based on the specific symptoms present in each individual.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_1
|
Symptoms of SETBP1 Haploinsufficiency Disorder
|
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified patients, the lack of large clinical studies and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.The majority of children with SETBP1-HD have intellectual disability that can range from mild to moderate to severe. The degree of intellectual disability may be hard to determine at first, because other symptoms may make evaluation difficult. Most children experience delays in reaching developmental milestones like sitting up or crawling. Speech delays are also common and can be significant. The degree of speech difficulty can vary. Some children may have problems moving the muscles needed to speak and forming the mouth movements needed to speak (apraxia of speech) while others may not speak at all (nonverbal).Additional symptoms include diminished muscle tone (hypotonia) so that infants may appear ‘floppy,’ and, less often, seizures. Other children may have increased muscle tone (hypertonia) so that muscles are stiff and hard to move. Some individuals may have difficulty planning and processing motor tasks (dyspraxia). Motor tasks are those that require the movement and coordination of the muscles. Affected individuals may experience fine and gross motor delays. Fine motor skills are those that require small movements involving the hands and wrists. Gross motor skills are those that require whole body movements and involve large muscles.Some individuals with SETBP1-HD have behavioral issues including attention deficit hyperactivity disorder (ADHD) and autism-like traits such as repetitive behaviors, fixation on objects, anxiety and poor social skills. Repetitive behaviors can include stereotypic hand movements, which include hand clapping, hand flapping, flicking hands, hand washing, fingers crossing, and frequent hand-to-mouth movements. Some children may show aggression or self-injury. Sleep disturbances, vision issues, digestive issues, and autism spectrum disorder (ASD) have also been reported in some individuals with SETBP1-HD.Affected individuals may have distinctive facial features including a long, pointed chin, which contributes to the face appearing longer than normal, mild drooping of the upper eyelid (mild ptosis), a prominent forehead, sparse eyebrows, a thin upper lip and abnormal fullness of the area around the eyes (periorbital fullness). Misalignment of the eyes (strabismus) has also been reported. The skull may appear shorter (brachycephaly) or longer (dolichocephaly) than usual.
|
Symptoms of SETBP1 Haploinsufficiency Disorder. Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified patients, the lack of large clinical studies and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.The majority of children with SETBP1-HD have intellectual disability that can range from mild to moderate to severe. The degree of intellectual disability may be hard to determine at first, because other symptoms may make evaluation difficult. Most children experience delays in reaching developmental milestones like sitting up or crawling. Speech delays are also common and can be significant. The degree of speech difficulty can vary. Some children may have problems moving the muscles needed to speak and forming the mouth movements needed to speak (apraxia of speech) while others may not speak at all (nonverbal).Additional symptoms include diminished muscle tone (hypotonia) so that infants may appear ‘floppy,’ and, less often, seizures. Other children may have increased muscle tone (hypertonia) so that muscles are stiff and hard to move. Some individuals may have difficulty planning and processing motor tasks (dyspraxia). Motor tasks are those that require the movement and coordination of the muscles. Affected individuals may experience fine and gross motor delays. Fine motor skills are those that require small movements involving the hands and wrists. Gross motor skills are those that require whole body movements and involve large muscles.Some individuals with SETBP1-HD have behavioral issues including attention deficit hyperactivity disorder (ADHD) and autism-like traits such as repetitive behaviors, fixation on objects, anxiety and poor social skills. Repetitive behaviors can include stereotypic hand movements, which include hand clapping, hand flapping, flicking hands, hand washing, fingers crossing, and frequent hand-to-mouth movements. Some children may show aggression or self-injury. Sleep disturbances, vision issues, digestive issues, and autism spectrum disorder (ASD) have also been reported in some individuals with SETBP1-HD.Affected individuals may have distinctive facial features including a long, pointed chin, which contributes to the face appearing longer than normal, mild drooping of the upper eyelid (mild ptosis), a prominent forehead, sparse eyebrows, a thin upper lip and abnormal fullness of the area around the eyes (periorbital fullness). Misalignment of the eyes (strabismus) has also been reported. The skull may appear shorter (brachycephaly) or longer (dolichocephaly) than usual.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_2
|
Causes of SETBP1 Haploinsufficiency Disorder
|
SETBP1-HD is caused by a variation in the SET binding protein 1 (SETBP1) gene, or in a small loss (microdeletion) of genetic material on chromosome 18 that contains the SETBP1 gene, but no other genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.The SETBP1 gene contains instructions to produce (encode) the SET binding protein 1. This protein is found in cells throughout the body including the brain and binds to another protein called SET. The exact function of this protein is not fully understood, but the SET binding protein 1 may be extremely important in the development of and/or function of brain cells. Affected individuals have a loss-of-function variation in the SETBP1 gene that leads to low levels of SET binding protein 1. A different type of variation, called a gain-of-function variation, can lead to overproduction of this protein. This leads to a different, more severe disorder called Schinzel Giedion syndrome (see the Related Disorders section below).In cases where a variation in SETBP1 is disease is causing the disorder, it almost always occurs as a new (sporadic or de novo) variation, which means that in nearly all instances the gene change has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. The disorder is usually not inherited from or “carried” by a healthy parent. However, affected individuals can pass on the altered gene in an autosomal dominant pattern.Dominant genetic disorders 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 mutated (changed) 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.
|
Causes of SETBP1 Haploinsufficiency Disorder. SETBP1-HD is caused by a variation in the SET binding protein 1 (SETBP1) gene, or in a small loss (microdeletion) of genetic material on chromosome 18 that contains the SETBP1 gene, but no other genes. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.The SETBP1 gene contains instructions to produce (encode) the SET binding protein 1. This protein is found in cells throughout the body including the brain and binds to another protein called SET. The exact function of this protein is not fully understood, but the SET binding protein 1 may be extremely important in the development of and/or function of brain cells. Affected individuals have a loss-of-function variation in the SETBP1 gene that leads to low levels of SET binding protein 1. A different type of variation, called a gain-of-function variation, can lead to overproduction of this protein. This leads to a different, more severe disorder called Schinzel Giedion syndrome (see the Related Disorders section below).In cases where a variation in SETBP1 is disease is causing the disorder, it almost always occurs as a new (sporadic or de novo) variation, which means that in nearly all instances the gene change has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. The disorder is usually not inherited from or “carried” by a healthy parent. However, affected individuals can pass on the altered gene in an autosomal dominant pattern.Dominant genetic disorders 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 mutated (changed) 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.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_3
|
Affects of SETBP1 Haploinsufficiency Disorder
|
SETBP1-HD affects males and females in equal numbers. More than 100 people from many different countries are known to have the disorder. The exact number of affected individuals is unknown. Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. SETBP1-HD is likely under-recognized and underdiagnosed.
|
Affects of SETBP1 Haploinsufficiency Disorder. SETBP1-HD affects males and females in equal numbers. More than 100 people from many different countries are known to have the disorder. The exact number of affected individuals is unknown. Rare disorders often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population. SETBP1-HD is likely under-recognized and underdiagnosed.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_4
|
Related disorders of SETBP1 Haploinsufficiency Disorder
|
Symptoms of the following disorders can be similar to those of SETBP1 haploinsufficiency disorder. Comparisons may be useful for a differential diagnosis.The SETBP1 gene is found on chromosome 18. Researchers defined a syndrome in which there is a loss of genetic material (deletion or monosomy) on the long arm, called q, on chromosome 18. This is known as deletion 18q(q12.2-q21.). This deletion includes the loss of the SETBP1 gene. Symptoms include diminished muscle tone (hypotonia), speech and language delays and behavioral problems.There are many disorders that can cause signs and symptoms similar to those seen in people with SETBP1-HD. These include better known disorders such as cerebral palsy, and a wide variety of other genetic neurodevelopmental disorders. The signs and symptoms of SETBP1-HD alone are not varied enough to distinguish the disorder from many of these other, similar disorders. Some affected individuals have symptoms that are consistent with those for individuals with an autism spectrum disorder. Childhood apraxia of speech is a disorder where children know what they want to say, but have difficulty forming the words. This may be because the brain has trouble directing the muscles of the mouth to move properly to be able to speak. It can occur as part of SETBP1-HD, or as part of other disorder or because of damage to the brain.Schinzel Giedion syndrome (SGS) is an extremely rare genetic disorder that is caused by a new (de novo), gain-of-function variation in the SETBP1 gene that is not inherited from the parents. Although SGS and SETBP1-HD are associated with the same gene, they are completely different disorders. Individuals with SGS develop characteristic facial features, skeletal abnormalities and obstruction of the tube that carries urine from the kidney to the bladder (ureter). This obstruction may lead to enlarged and damaged kidneys (hydronephrosis). Additional symptoms include excessive hair-growth (hypertrichosis), a flat midface (midface retraction), seizures, clubfeet, broad ribs, profound intellectual disability and short arms and legs. SGS is a severe progressive syndrome and most affected individuals do not survive infancy. (For more information on this disorder, choose “Schinzel Giedeon” as your search term in the Rare Disease Database.)
|
Related disorders of SETBP1 Haploinsufficiency Disorder. Symptoms of the following disorders can be similar to those of SETBP1 haploinsufficiency disorder. Comparisons may be useful for a differential diagnosis.The SETBP1 gene is found on chromosome 18. Researchers defined a syndrome in which there is a loss of genetic material (deletion or monosomy) on the long arm, called q, on chromosome 18. This is known as deletion 18q(q12.2-q21.). This deletion includes the loss of the SETBP1 gene. Symptoms include diminished muscle tone (hypotonia), speech and language delays and behavioral problems.There are many disorders that can cause signs and symptoms similar to those seen in people with SETBP1-HD. These include better known disorders such as cerebral palsy, and a wide variety of other genetic neurodevelopmental disorders. The signs and symptoms of SETBP1-HD alone are not varied enough to distinguish the disorder from many of these other, similar disorders. Some affected individuals have symptoms that are consistent with those for individuals with an autism spectrum disorder. Childhood apraxia of speech is a disorder where children know what they want to say, but have difficulty forming the words. This may be because the brain has trouble directing the muscles of the mouth to move properly to be able to speak. It can occur as part of SETBP1-HD, or as part of other disorder or because of damage to the brain.Schinzel Giedion syndrome (SGS) is an extremely rare genetic disorder that is caused by a new (de novo), gain-of-function variation in the SETBP1 gene that is not inherited from the parents. Although SGS and SETBP1-HD are associated with the same gene, they are completely different disorders. Individuals with SGS develop characteristic facial features, skeletal abnormalities and obstruction of the tube that carries urine from the kidney to the bladder (ureter). This obstruction may lead to enlarged and damaged kidneys (hydronephrosis). Additional symptoms include excessive hair-growth (hypertrichosis), a flat midface (midface retraction), seizures, clubfeet, broad ribs, profound intellectual disability and short arms and legs. SGS is a severe progressive syndrome and most affected individuals do not survive infancy. (For more information on this disorder, choose “Schinzel Giedeon” as your search term in the Rare Disease Database.)
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_5
|
Diagnosis of SETBP1 Haploinsufficiency Disorder
|
A diagnosis of SETBP1-HD is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Children with mild or moderate intellectual disability and speech development problems, but no other anomalies may be suspected of having SETBP1-HD. A diagnosis is confirmed through molecular genetic testing.Clinical Testing and WorkupMolecular genetic testing can detect disease-causing variations in the SETBP1 gene but is available only as a diagnostic service at specialized laboratories. Doctors will take a blood sample of individuals suspected of having a SETBP1-HD and the sample will undergo whole exome sequencing (WES). WES is a molecular genetic testing method that examines the genes in humans that contain instructions for creating proteins (protein-encoding genes). This is called the exome. WES can detect variations in the SETBP1 gene that are known to cause disease, or variations in other genes known to cause symptoms similar to this disorder.Affected individuals may undergo additional tests before molecular genetic testing to rule other conditions, or after molecular genetic testing to assess the extent of the disease. An advanced imaging technique called magnetic resonance imaging (MRI) may be recommended. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues including the brain.Neurologic examination is important for individuals with the symptoms of SETBP1-HD. Neurologic examination helps identify the specific features affecting a person. Laboratory tests, neurophysiologic testing and neuroimaging; routine laboratory studies (such as blood counts, serum electrolytes, and tests of kidney, liver, and endocrine functions); and analysis of cerebrospinal fluid (obtained by “spinal tap”) may be conducted to help exclude alternate and co-existing diagnoses.
|
Diagnosis of SETBP1 Haploinsufficiency Disorder. A diagnosis of SETBP1-HD is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. Children with mild or moderate intellectual disability and speech development problems, but no other anomalies may be suspected of having SETBP1-HD. A diagnosis is confirmed through molecular genetic testing.Clinical Testing and WorkupMolecular genetic testing can detect disease-causing variations in the SETBP1 gene but is available only as a diagnostic service at specialized laboratories. Doctors will take a blood sample of individuals suspected of having a SETBP1-HD and the sample will undergo whole exome sequencing (WES). WES is a molecular genetic testing method that examines the genes in humans that contain instructions for creating proteins (protein-encoding genes). This is called the exome. WES can detect variations in the SETBP1 gene that are known to cause disease, or variations in other genes known to cause symptoms similar to this disorder.Affected individuals may undergo additional tests before molecular genetic testing to rule other conditions, or after molecular genetic testing to assess the extent of the disease. An advanced imaging technique called magnetic resonance imaging (MRI) may be recommended. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues including the brain.Neurologic examination is important for individuals with the symptoms of SETBP1-HD. Neurologic examination helps identify the specific features affecting a person. Laboratory tests, neurophysiologic testing and neuroimaging; routine laboratory studies (such as blood counts, serum electrolytes, and tests of kidney, liver, and endocrine functions); and analysis of cerebrospinal fluid (obtained by “spinal tap”) may be conducted to help exclude alternate and co-existing diagnoses.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1106_6
|
Therapies of SETBP1 Haploinsufficiency Disorder
|
TreatmentThe treatment of SETBP1-HD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating disorders of the brain and central nervous system in children (pediatric neurologists) and adults (neurologists), speech therapists, physical therapists, occupational therapists and other healthcare professionals may need to systematically and comprehensively plan treatment.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with SETBP1-HD.Following an initial diagnosis, a developmental assessment may be performed and appropriate occupational, physical and speech therapies be instituted. Speech therapy is required and can include one-on-one sessions with a speech therapist, combined sessions where children learn language and social skills as a group, and the use of augmentative and alternative communication (AAC). AAC includes the use of high-tech and low-tech communication devices that can help children express thoughts, wants, needs and ideas.Children with SETBP1-HD disorder should be enrolled in speech therapy in the first year of life. Multi-modal communication, such as sign language or communication devices support language acquisition prior to speech developing. Children need speech motor therapies to develop verbal speech, but also phonological interventions focused on early literacy awareness and approaches targeting language comprehension as well as production.A full behavioral assessment may be necessary and can help to identify triggers of aggressive or self-injurious actions. Behavioral issues including ADHD, repetitive behaviors, depression, anxiety, aggression and self-injury can be treated with standard medications for these conditions.
Periodic reassessments and adjustment of services should be provided with all children. Additional medical, social and/or vocational services including specialized learning programs may be necessary.
Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well. The organizations listed in the Resources section provide support and information on SETBP1-HD or specific symptoms.
|
Therapies of SETBP1 Haploinsufficiency Disorder. TreatmentThe treatment of SETBP1-HD is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating disorders of the brain and central nervous system in children (pediatric neurologists) and adults (neurologists), speech therapists, physical therapists, occupational therapists and other healthcare professionals may need to systematically and comprehensively plan treatment.There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with SETBP1-HD.Following an initial diagnosis, a developmental assessment may be performed and appropriate occupational, physical and speech therapies be instituted. Speech therapy is required and can include one-on-one sessions with a speech therapist, combined sessions where children learn language and social skills as a group, and the use of augmentative and alternative communication (AAC). AAC includes the use of high-tech and low-tech communication devices that can help children express thoughts, wants, needs and ideas.Children with SETBP1-HD disorder should be enrolled in speech therapy in the first year of life. Multi-modal communication, such as sign language or communication devices support language acquisition prior to speech developing. Children need speech motor therapies to develop verbal speech, but also phonological interventions focused on early literacy awareness and approaches targeting language comprehension as well as production.A full behavioral assessment may be necessary and can help to identify triggers of aggressive or self-injurious actions. Behavioral issues including ADHD, repetitive behaviors, depression, anxiety, aggression and self-injury can be treated with standard medications for these conditions.
Periodic reassessments and adjustment of services should be provided with all children. Additional medical, social and/or vocational services including specialized learning programs may be necessary.
Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well. The organizations listed in the Resources section provide support and information on SETBP1-HD or specific symptoms.
| 1,106 |
SETBP1 Haploinsufficiency Disorder
|
nord_1107_0
|
Overview of Setleis Syndrome
|
Setleis syndrome is an extremely rare inherited disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area that may be apparent at birth (congenital). Most affected infants have multiple, scar-like, circular depressions on both temples (bitemporal). These marks closely resemble those made when forceps are used to assist delivery. In addition, affected infants may have puffy, wrinkled skin around the eyes (periorbital) and/or abnormalities of the eyelashes, eyebrows, and eyelids. Infants with Setleis syndrome may be missing eyelashes on both the upper and lower lids, or they may have multiple rows of lashes on the upper lids but none on the lower lids. In addition, in some cases, the bridge of the nose may appear flat, while the tip may appear unusually rounded (bulbous). Affected infants often have loose, excessive (redundant) skin, particularly in the area of the nose and the chin. Due to such facial abnormalities, infants with Setleis syndrome may have an aged and/or “leonine” (lion-like) appearance. The range and severity of symptoms may vary from case to case. Most cases of Setleis syndrome are thought to be inherited as an autosomal recessive genetic trait.
|
Overview of Setleis Syndrome. Setleis syndrome is an extremely rare inherited disorder that belongs to a group of diseases known as ectodermal dysplasias. Ectodermal dysplasias typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area that may be apparent at birth (congenital). Most affected infants have multiple, scar-like, circular depressions on both temples (bitemporal). These marks closely resemble those made when forceps are used to assist delivery. In addition, affected infants may have puffy, wrinkled skin around the eyes (periorbital) and/or abnormalities of the eyelashes, eyebrows, and eyelids. Infants with Setleis syndrome may be missing eyelashes on both the upper and lower lids, or they may have multiple rows of lashes on the upper lids but none on the lower lids. In addition, in some cases, the bridge of the nose may appear flat, while the tip may appear unusually rounded (bulbous). Affected infants often have loose, excessive (redundant) skin, particularly in the area of the nose and the chin. Due to such facial abnormalities, infants with Setleis syndrome may have an aged and/or “leonine” (lion-like) appearance. The range and severity of symptoms may vary from case to case. Most cases of Setleis syndrome are thought to be inherited as an autosomal recessive genetic trait.
| 1,107 |
Setleis Syndrome
|
nord_1107_1
|
Symptoms of Setleis Syndrome
|
Setleis syndrome, an extremely rare inherited disorder, belongs to a group of diseases known as ectodermal dysplasias that typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area. The range and severity of symptoms may vary from case to case.Infants with Setleis syndrome have multiple, scar-like, circular depressions on both temples (bitemporal) that strongly resemble the marks made during a forceps delivery. According to some researchers, these “forceps marks” may represent aplasia cutis congenita, a rare condition characterized by failure of development of skin and hair in certain areas (localized), most often on the scalp; absence of certain structures just below the skin's surface (e.g., sweat glands); and/or the development of scar tissue or a thin membrane over the affected area. For example, in some infants with Setleis syndrome, the outermost layer of skin (epidermis) in the temple area may be abnormally thin and the hair follicles, sweat glands, and sebaceous glands normally located within the thick inner layer of skin (dermis) may be absent. The sebaceous glands produce a thick, oily substance (sebum) that helps the skin retain body heat and prevent the evaporation of sweat. In addition, in most infants with Setleis syndrome the skin around the eyes (periorbital) is puffy and wrinkled, giving them an aged appearance. In some cases, affected infants may also have an abnormally prominent forehead (frontal bossing) and eyebrows that grow upward and outward, but have sparse side growth. In some cases, as a result of characteristic facial features, affected infants may have a coarse or “leonine” (lion-like) facial appearance.In most cases, infants with Setleis syndrome also have abnormalities of the eyelashes such as absence of the eyelashes on both the upper and lower lids or multiple rows of eyelashes on the upper lids (distichiasis) and none on the lower lids (astichiasis). In some cases, abnormalities of the eyelashes may lead to redness, inflammation, and/or swelling of the eyelids with scaly skin forming at the ends of the eyelids and flakes of discharge collecting in the corners or on the lashes. Eventually, infections may occur at the base of the lashes (blepharitis), and the eyes themselves may become red. In many cases, affected infants may have other abnormalities affecting the eyes. For example, the transparent, thin membrane that protects and helps lubricate the eyelids and whites of the eyes (conjunctiva) may become inflamed (conjunctivitis). In some cases, infants with Setleis syndrome may have downward slanting eyelid slits (palpebral fissures), excess folds of skin on either side of the nose that cover the eyes' inner corners (epicanthal folds), or, in rare cases, crossed eyes (strabismus). Infants with Setleis syndrome may also have additional abnormalities of the facial area. The bridge of the nose may appear flat, while the tip of the nose may appear abnormally rounded (bulbous). In some cases, the wall that divides the two chambers of the nose (nasal septum) may extend below the nostrils (alae nasae). In most cases, infants have a downturned mouth, an abnormally prominent upper lip, and/or unusually thick lips. In some cases, abnormal thickness of the lips may be due, in part, to increased mobility of the skin. In addition, affected children may have loose, excessive (redundant) facial skin, and the skin of the nose and the chin may appear abnormally flexible or “rubbery.” Some affected individuals may also have small, malformed ears and/or an abnormal groove or furrow in the chin (cleft chin). Facial abnormalities may become less pronounced as affected children age. In addition, many individuals with Setleis syndrome have distinctive abnormalities involving hair growth. Affected individuals may have thin scalp hair, abnormal bald patches on the scalp (alopecia), and/or a low frontal hairline.In a few cases, children with Setleis syndrome have additional abnormalities. For example, they may have patches of skin that appear darker or lighter in various areas of the body (hyper- or hypopigmentation), such as light brown “coffee-colored” discolorations (cafe-au-lait spots) or patches of skin that lack color (vitiligo). In some cases, affected individuals have abnormal creases or lines on the palms of the hands (palmar creases). Some researchers believe that Setleis syndrome is a form of focal facial dermal dysplasia (FFDD), which has been described as a group of rare inherited disorders that may be characterized by the presence of scar-like depressions on the temples at birth, potentially in association with additional facial abnormalities. For more information, please see the “Related Disorders” section of this report.
|
Symptoms of Setleis Syndrome. Setleis syndrome, an extremely rare inherited disorder, belongs to a group of diseases known as ectodermal dysplasias that typically affect the hair, teeth, nails, and/or skin. Setleis syndrome is characterized by distinctive abnormalities of the facial area. The range and severity of symptoms may vary from case to case.Infants with Setleis syndrome have multiple, scar-like, circular depressions on both temples (bitemporal) that strongly resemble the marks made during a forceps delivery. According to some researchers, these “forceps marks” may represent aplasia cutis congenita, a rare condition characterized by failure of development of skin and hair in certain areas (localized), most often on the scalp; absence of certain structures just below the skin's surface (e.g., sweat glands); and/or the development of scar tissue or a thin membrane over the affected area. For example, in some infants with Setleis syndrome, the outermost layer of skin (epidermis) in the temple area may be abnormally thin and the hair follicles, sweat glands, and sebaceous glands normally located within the thick inner layer of skin (dermis) may be absent. The sebaceous glands produce a thick, oily substance (sebum) that helps the skin retain body heat and prevent the evaporation of sweat. In addition, in most infants with Setleis syndrome the skin around the eyes (periorbital) is puffy and wrinkled, giving them an aged appearance. In some cases, affected infants may also have an abnormally prominent forehead (frontal bossing) and eyebrows that grow upward and outward, but have sparse side growth. In some cases, as a result of characteristic facial features, affected infants may have a coarse or “leonine” (lion-like) facial appearance.In most cases, infants with Setleis syndrome also have abnormalities of the eyelashes such as absence of the eyelashes on both the upper and lower lids or multiple rows of eyelashes on the upper lids (distichiasis) and none on the lower lids (astichiasis). In some cases, abnormalities of the eyelashes may lead to redness, inflammation, and/or swelling of the eyelids with scaly skin forming at the ends of the eyelids and flakes of discharge collecting in the corners or on the lashes. Eventually, infections may occur at the base of the lashes (blepharitis), and the eyes themselves may become red. In many cases, affected infants may have other abnormalities affecting the eyes. For example, the transparent, thin membrane that protects and helps lubricate the eyelids and whites of the eyes (conjunctiva) may become inflamed (conjunctivitis). In some cases, infants with Setleis syndrome may have downward slanting eyelid slits (palpebral fissures), excess folds of skin on either side of the nose that cover the eyes' inner corners (epicanthal folds), or, in rare cases, crossed eyes (strabismus). Infants with Setleis syndrome may also have additional abnormalities of the facial area. The bridge of the nose may appear flat, while the tip of the nose may appear abnormally rounded (bulbous). In some cases, the wall that divides the two chambers of the nose (nasal septum) may extend below the nostrils (alae nasae). In most cases, infants have a downturned mouth, an abnormally prominent upper lip, and/or unusually thick lips. In some cases, abnormal thickness of the lips may be due, in part, to increased mobility of the skin. In addition, affected children may have loose, excessive (redundant) facial skin, and the skin of the nose and the chin may appear abnormally flexible or “rubbery.” Some affected individuals may also have small, malformed ears and/or an abnormal groove or furrow in the chin (cleft chin). Facial abnormalities may become less pronounced as affected children age. In addition, many individuals with Setleis syndrome have distinctive abnormalities involving hair growth. Affected individuals may have thin scalp hair, abnormal bald patches on the scalp (alopecia), and/or a low frontal hairline.In a few cases, children with Setleis syndrome have additional abnormalities. For example, they may have patches of skin that appear darker or lighter in various areas of the body (hyper- or hypopigmentation), such as light brown “coffee-colored” discolorations (cafe-au-lait spots) or patches of skin that lack color (vitiligo). In some cases, affected individuals have abnormal creases or lines on the palms of the hands (palmar creases). Some researchers believe that Setleis syndrome is a form of focal facial dermal dysplasia (FFDD), which has been described as a group of rare inherited disorders that may be characterized by the presence of scar-like depressions on the temples at birth, potentially in association with additional facial abnormalities. For more information, please see the “Related Disorders” section of this report.
| 1,107 |
Setleis Syndrome
|
nord_1107_2
|
Causes of Setleis Syndrome
|
In most cases, Setleis syndrome is thought to be inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from 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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. Some cases of Setleis syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 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.A number of cases of Setleis syndrome have been reported in which a parent of an affected individual as demonstrated mild manifestations of the disorder. As a result, some researchers suspect that, in some cases, Setleis syndrome may be inherited as an autosomal dominant trait with great differences in manifestation from case to case (variable expression) and may not be manifested in all those who inherit the gene (incomplete penetrance).In cases of possible autosomal dominant inheritance, researchers have proposed that Setleis syndrome may be the same disorder as focal facial dermal dysplasia type I, a rare disorder that is inherited as an autosomal dominant trait with variable expressivity. For more information, please see the “Related Disorders” section of this report.
|
Causes of Setleis Syndrome. In most cases, Setleis syndrome is thought to be inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from 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% 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 normal genes from both parents and be genetically normal for that particular trait is 25%. Some cases of Setleis syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 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.A number of cases of Setleis syndrome have been reported in which a parent of an affected individual as demonstrated mild manifestations of the disorder. As a result, some researchers suspect that, in some cases, Setleis syndrome may be inherited as an autosomal dominant trait with great differences in manifestation from case to case (variable expression) and may not be manifested in all those who inherit the gene (incomplete penetrance).In cases of possible autosomal dominant inheritance, researchers have proposed that Setleis syndrome may be the same disorder as focal facial dermal dysplasia type I, a rare disorder that is inherited as an autosomal dominant trait with variable expressivity. For more information, please see the “Related Disorders” section of this report.
| 1,107 |
Setleis Syndrome
|
nord_1107_3
|
Affects of Setleis Syndrome
|
Setleis syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature. The majority of these cases have occurred in individuals from Puerto Rico.
|
Affects of Setleis Syndrome. Setleis syndrome is an extremely rare inherited disorder that, in theory, affects males and females in equal numbers. Approximately 20 cases have been reported in the medical literature. The majority of these cases have occurred in individuals from Puerto Rico.
| 1,107 |
Setleis Syndrome
|
nord_1107_4
|
Related disorders of Setleis Syndrome
|
Symptoms of the following disorders can be similar to those of Setleis syndrome. Comparisons may be useful for a differential diagnosis: Focal facial dermal dysplasia (FFDD) type I, also known as Brauer syndrome, is a rare inherited disorder characterized by scar-like depressions on the temples, similar to those that may be caused by forceps when used during delivery. In addition, affected individuals may have wrinkled, puffy skin in the temple area and teardrop-shaped (guttate) lesions on the chin and middle of the forehead. Focal facial dermal dysplasia type I is thought to be inherited as an autosomal dominant genetic trait with variable expressivity. There is some confusion in the medical literature concerning the relationship of focal facial dermal dysplasia type I and Setleis syndrome. While some researchers believe that FFDD Type I and Setleis syndrome are different forms of focal facial dermal dysplasia, others suspect that they represent the same disease entity. Ectodermal dysplasias (EDs) are a group of rare inherited multisystem disorders that typically affect the hair, teeth, nails, and/or skin. Several other ectodermal dysplasia disorders may be characterized by sparse or absent hair, absence or improper functioning of sweat glands, skin abnormalities, malformations of the nose, and/or other abnormalities similar to those associated with Setleis syndrome. (For more information on these disorders, choose “Ectodermal Dysplasias” or the exact disease name in question as your search term in the Rare Disease Database.)
|
Related disorders of Setleis Syndrome. Symptoms of the following disorders can be similar to those of Setleis syndrome. Comparisons may be useful for a differential diagnosis: Focal facial dermal dysplasia (FFDD) type I, also known as Brauer syndrome, is a rare inherited disorder characterized by scar-like depressions on the temples, similar to those that may be caused by forceps when used during delivery. In addition, affected individuals may have wrinkled, puffy skin in the temple area and teardrop-shaped (guttate) lesions on the chin and middle of the forehead. Focal facial dermal dysplasia type I is thought to be inherited as an autosomal dominant genetic trait with variable expressivity. There is some confusion in the medical literature concerning the relationship of focal facial dermal dysplasia type I and Setleis syndrome. While some researchers believe that FFDD Type I and Setleis syndrome are different forms of focal facial dermal dysplasia, others suspect that they represent the same disease entity. Ectodermal dysplasias (EDs) are a group of rare inherited multisystem disorders that typically affect the hair, teeth, nails, and/or skin. Several other ectodermal dysplasia disorders may be characterized by sparse or absent hair, absence or improper functioning of sweat glands, skin abnormalities, malformations of the nose, and/or other abnormalities similar to those associated with Setleis syndrome. (For more information on these disorders, choose “Ectodermal Dysplasias” or the exact disease name in question as your search term in the Rare Disease Database.)
| 1,107 |
Setleis Syndrome
|
nord_1107_5
|
Diagnosis of Setleis Syndrome
|
Setleis syndrome is usually diagnosed shortly after birth based upon a thorough clinical evaluation and identification of characteristic features, such as distinctive scar-like, circular depressions on both temples; an aged and/or "leonine" facial appearance; and characteristic abnormalities of the eyelashes, eyebrows, and eyelids. It is possible that microscopic examination of small samples of skin tissue (biopsy) from the temples may reveal abnormal thinning of the outer layer of the skin (epidermis) and absence of certain specialized structures normally located within the inner layer of the skin (e.g., sweat glands, sebaceous glands, hair follicles).
|
Diagnosis of Setleis Syndrome. Setleis syndrome is usually diagnosed shortly after birth based upon a thorough clinical evaluation and identification of characteristic features, such as distinctive scar-like, circular depressions on both temples; an aged and/or "leonine" facial appearance; and characteristic abnormalities of the eyelashes, eyebrows, and eyelids. It is possible that microscopic examination of small samples of skin tissue (biopsy) from the temples may reveal abnormal thinning of the outer layer of the skin (epidermis) and absence of certain specialized structures normally located within the inner layer of the skin (e.g., sweat glands, sebaceous glands, hair follicles).
| 1,107 |
Setleis Syndrome
|
nord_1107_6
|
Therapies of Setleis Syndrome
|
TreatmentTreatment is directed toward the specific symptoms that are apparent in each individual. In some cases, removal of excess eyelashes (epilation) that are growing toward the eyes may help reduce eye irritation. Blepharitis is treated symptomatically. Because facial abnormalities tend to lessen as an affected child ages, surgery may be postponed to monitor facial development. However, in some cases, corrective surgery may eventually be performed. Other treatment for this disorder is symptomatic and supportive.Genetic counseling is of benefit for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be associated with Setleis syndrome.
|
Therapies of Setleis Syndrome. TreatmentTreatment is directed toward the specific symptoms that are apparent in each individual. In some cases, removal of excess eyelashes (epilation) that are growing toward the eyes may help reduce eye irritation. Blepharitis is treated symptomatically. Because facial abnormalities tend to lessen as an affected child ages, surgery may be postponed to monitor facial development. However, in some cases, corrective surgery may eventually be performed. Other treatment for this disorder is symptomatic and supportive.Genetic counseling is of benefit for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be associated with Setleis syndrome.
| 1,107 |
Setleis Syndrome
|
nord_1108_0
|
Overview of Severe Chronic Neutropenia
|
Severe chronic neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of certain white blood cells (neutrophils) in the bloodstream (neutropenia) not explained by medication use, infections or another underlying health condition like blood cancers or systemic autoimmune diseases associated with neutropenia. Neutrophils play an essential role in fighting bacterial infections by surrounding and destroying invading bacteria (phagocytosis). Symptoms associated with severe chronic neutropenia include recurring fevers, mouth sores (ulcers), inflammation of the tissues that surround and support the teeth (periodontitis) and inflammation of the sinuses (sinusitis), throat (pharyngitis) and/or ear (otitis). Due to low levels of neutrophils, affected individuals may be more susceptible to recurring bacterial infections that, in some patients, may result in life-threatening complications. SCN may last for months or years and can affect both children and adults. Clinicians recognize three forms of the disorder: congenital, autoimmune and idiopathic neutropenia. The term idiopathic neutropenia is used when severe chronic neutropenia occurs for unknown reasons.
|
Overview of Severe Chronic Neutropenia. Severe chronic neutropenia (SCN) is a rare blood disorder characterized by abnormally low levels of certain white blood cells (neutrophils) in the bloodstream (neutropenia) not explained by medication use, infections or another underlying health condition like blood cancers or systemic autoimmune diseases associated with neutropenia. Neutrophils play an essential role in fighting bacterial infections by surrounding and destroying invading bacteria (phagocytosis). Symptoms associated with severe chronic neutropenia include recurring fevers, mouth sores (ulcers), inflammation of the tissues that surround and support the teeth (periodontitis) and inflammation of the sinuses (sinusitis), throat (pharyngitis) and/or ear (otitis). Due to low levels of neutrophils, affected individuals may be more susceptible to recurring bacterial infections that, in some patients, may result in life-threatening complications. SCN may last for months or years and can affect both children and adults. Clinicians recognize three forms of the disorder: congenital, autoimmune and idiopathic neutropenia. The term idiopathic neutropenia is used when severe chronic neutropenia occurs for unknown reasons.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_1
|
Symptoms of Severe Chronic Neutropenia
|
Symptoms and physical findings associated with severe chronic neutropenia vary greatly depending on how low the level of neutrophils in the blood falls. As earlier noted, the three main subdivisions of severe chronic neutropenia are congenital, autoimmune and idiopathic.The congenital forms of severe chronic neutropenia are often the most severe of all types of SCN and can be detected by doing a blood count in infancy or during early childhood.Findings common to all congenital forms of SCN include fevers; ear infections; acute inflammation of the lungs (pneumonia); skin infections; and inflammation of the delicate mucous membranes that line the mouth (stomatitis), the gums (gingivitis) and/or the tissue that surrounds and supports the teeth (periodontitis). Recurrent oral ulcerations are also common. Some patients may experience premature loss of teeth. Individuals with congenital forms of severe chronic neutropenia are especially susceptible to various bacterial infections that affect the skin, digestive (gastrointestinal) tract and respiratory system, with the source of bacteria usually from the patient's own skin and gut flora. Such bacterial infections vary in severity and, in some patients may result in life-threatening complications. Importantly, patients with congenital neutropenia still have normal immunity to viruses and so are no more susceptible to viral infections than the average person and can receive all immunizations, including live virus vaccines. Patients with congenital forms of SCN are at greater risk of developing leukemia than are other people, especially in cases associated with certain gene mutations and cases that require higher medication doses. Yearly bone marrow examinations where chromosomes are examined can detect leukemia at its earliest development.In cyclic neutropenia, a rare form of congenital neutronia, the primary finding is a periodic severe decrease in the levels of neutrophils. In most patients, episodes of severe neutropenia recur on an average of every 21 days (hence “cyclic”) and may last for approximately three to six days. The cycling period usually remains constant and consistent among affected individuals, but the severity of the low point may improve with age. Although other forms of neutropenia can show striking variability of neutrophil counts, only cyclic neutropenia causes such consistent, lifelong cycling of neutrophils, and often other types of blood cells.Autoimmune neutropenia usually strikes children between the ages of 6 months and 4 years and is the most common form of SCN in this age group. Less frequently, adults may develop this disorder, with a peak incidence from 20 to 30 years of age. This disorder is characterized by the presence of neutrophil-specific antibodies in the blood that increase the rate of destruction of the patient’s neutrophils. Although the blood level of neutrophils can be very low in children with autoimmune neutropenia, they are only rarely affected by severe bacterial infections and neutropenia usually resolves without treatment several months to years after onset. Unfortunately, spontaneous remission of autoimmune SCN is not at all common in the adult-onset version but clinical symptoms are usually mild and only occasionally severe. Other potential findings with autoimmune neutropenia in adults are low red blood cells (anemia) and platelet levels (thrombocytopenia). Autoimmune neutropenia is distinct from congenital neutropenia in terms of the cause of neutropenia. The congenital neutropenias arise from the failure of the bone marrow to produce adequate numbers of neutrophils which circulate in the blood. Autoimmune neutropenias, due to destruction of neutrophils in the blood, usually feature a reserve pool of neutrophils in the bone marrow and good delivery of neutrophils to sites of bacterial invation, leading to the observed low incidence of serious infection.Chronic idiopathic neutropenia refers to a group of disorders that cannot be classified into one of the other categories of neutropenia. The exact cause of these disorders is not known (idiopathic), but most likely represent an autoimmune process in many patients. In most patients, the symptoms associated with idiopathic neutropenia are less severe than those associated with congenital neutropenia and may not require specific treatment. However, in some severely affected patients with idiopathic neutropenia, infections may result in life-threatening complications.
|
Symptoms of Severe Chronic Neutropenia. Symptoms and physical findings associated with severe chronic neutropenia vary greatly depending on how low the level of neutrophils in the blood falls. As earlier noted, the three main subdivisions of severe chronic neutropenia are congenital, autoimmune and idiopathic.The congenital forms of severe chronic neutropenia are often the most severe of all types of SCN and can be detected by doing a blood count in infancy or during early childhood.Findings common to all congenital forms of SCN include fevers; ear infections; acute inflammation of the lungs (pneumonia); skin infections; and inflammation of the delicate mucous membranes that line the mouth (stomatitis), the gums (gingivitis) and/or the tissue that surrounds and supports the teeth (periodontitis). Recurrent oral ulcerations are also common. Some patients may experience premature loss of teeth. Individuals with congenital forms of severe chronic neutropenia are especially susceptible to various bacterial infections that affect the skin, digestive (gastrointestinal) tract and respiratory system, with the source of bacteria usually from the patient's own skin and gut flora. Such bacterial infections vary in severity and, in some patients may result in life-threatening complications. Importantly, patients with congenital neutropenia still have normal immunity to viruses and so are no more susceptible to viral infections than the average person and can receive all immunizations, including live virus vaccines. Patients with congenital forms of SCN are at greater risk of developing leukemia than are other people, especially in cases associated with certain gene mutations and cases that require higher medication doses. Yearly bone marrow examinations where chromosomes are examined can detect leukemia at its earliest development.In cyclic neutropenia, a rare form of congenital neutronia, the primary finding is a periodic severe decrease in the levels of neutrophils. In most patients, episodes of severe neutropenia recur on an average of every 21 days (hence “cyclic”) and may last for approximately three to six days. The cycling period usually remains constant and consistent among affected individuals, but the severity of the low point may improve with age. Although other forms of neutropenia can show striking variability of neutrophil counts, only cyclic neutropenia causes such consistent, lifelong cycling of neutrophils, and often other types of blood cells.Autoimmune neutropenia usually strikes children between the ages of 6 months and 4 years and is the most common form of SCN in this age group. Less frequently, adults may develop this disorder, with a peak incidence from 20 to 30 years of age. This disorder is characterized by the presence of neutrophil-specific antibodies in the blood that increase the rate of destruction of the patient’s neutrophils. Although the blood level of neutrophils can be very low in children with autoimmune neutropenia, they are only rarely affected by severe bacterial infections and neutropenia usually resolves without treatment several months to years after onset. Unfortunately, spontaneous remission of autoimmune SCN is not at all common in the adult-onset version but clinical symptoms are usually mild and only occasionally severe. Other potential findings with autoimmune neutropenia in adults are low red blood cells (anemia) and platelet levels (thrombocytopenia). Autoimmune neutropenia is distinct from congenital neutropenia in terms of the cause of neutropenia. The congenital neutropenias arise from the failure of the bone marrow to produce adequate numbers of neutrophils which circulate in the blood. Autoimmune neutropenias, due to destruction of neutrophils in the blood, usually feature a reserve pool of neutrophils in the bone marrow and good delivery of neutrophils to sites of bacterial invation, leading to the observed low incidence of serious infection.Chronic idiopathic neutropenia refers to a group of disorders that cannot be classified into one of the other categories of neutropenia. The exact cause of these disorders is not known (idiopathic), but most likely represent an autoimmune process in many patients. In most patients, the symptoms associated with idiopathic neutropenia are less severe than those associated with congenital neutropenia and may not require specific treatment. However, in some severely affected patients with idiopathic neutropenia, infections may result in life-threatening complications.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_2
|
Causes of Severe Chronic Neutropenia
|
GeneticsCongenital forms of severe chronic neutropenia may be inherited in either an autosomal dominant, autosomal recessive or X-linked (sex-linked) pattern. However, some cases of congenital neutropenia are the result of acquired spontaneous mutations that aren't inherited. Changes or mutations in the ELANE gene are the most common cause of the autosomal dominant form of severe congenital neutropenia and virtually all cases of cyclic neutropenia. Mutations in the SRP54 and GFI1 genes are also linked to rare autosomal dominant congenital neutropenia cases. The autosomal recessive form of congenital neutropenia can be caused by mutations in the genes HAX1 (Kostmann disease), G6PC3, JAGN1, among others. Mutations in these genes can cause isolated neutropenia or be associated with other signs/symptoms such as neurological deficits with HAX1 mutations or cardiac abnormalities with G6PC3 mutations. Very rare mutations in the WAS gene can cause X-linked congenital neutropenia in males.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 mutation 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.Recessive genetic disorders occur when an individual inherits an alteration in a gene for the condition 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 altered 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 is 25 percent. The risk is the same for males and females.X-linked genetic disorders are conditions caused by an altered gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an aleterd gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. If a male with an X-linked disorder is able to reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.Most cases of chronic idiopathic neutropenia and autoimmune neutropenias are not inherited, although there can be a familial predisposition to adult autoimmune disease, and some cases of persistent childhood autoimmune neutropenia are associated with inherited disorders of the immune system.Other disorders associated with SCN include Shwachman-Diamond syndrome, glycogen storage disease type 1b, and multiple other syndromes affecting the bone marrow and other organs.
|
Causes of Severe Chronic Neutropenia. GeneticsCongenital forms of severe chronic neutropenia may be inherited in either an autosomal dominant, autosomal recessive or X-linked (sex-linked) pattern. However, some cases of congenital neutropenia are the result of acquired spontaneous mutations that aren't inherited. Changes or mutations in the ELANE gene are the most common cause of the autosomal dominant form of severe congenital neutropenia and virtually all cases of cyclic neutropenia. Mutations in the SRP54 and GFI1 genes are also linked to rare autosomal dominant congenital neutropenia cases. The autosomal recessive form of congenital neutropenia can be caused by mutations in the genes HAX1 (Kostmann disease), G6PC3, JAGN1, among others. Mutations in these genes can cause isolated neutropenia or be associated with other signs/symptoms such as neurological deficits with HAX1 mutations or cardiac abnormalities with G6PC3 mutations. Very rare mutations in the WAS gene can cause X-linked congenital neutropenia in males.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 mutation 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.Recessive genetic disorders occur when an individual inherits an alteration in a gene for the condition 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 altered 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 is 25 percent. The risk is the same for males and females.X-linked genetic disorders are conditions caused by an altered gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an aleterd gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. If a male with an X-linked disorder is able to reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.Most cases of chronic idiopathic neutropenia and autoimmune neutropenias are not inherited, although there can be a familial predisposition to adult autoimmune disease, and some cases of persistent childhood autoimmune neutropenia are associated with inherited disorders of the immune system.Other disorders associated with SCN include Shwachman-Diamond syndrome, glycogen storage disease type 1b, and multiple other syndromes affecting the bone marrow and other organs.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_3
|
Affects of Severe Chronic Neutropenia
|
Severe chronic neutropenia is a rare blood disorder that appears to affect females more than males in its idiopathic and autoimmune forms, with less discrepancy between the sexes in congenital forms. Both children and adults may be affected. Severe congenital neutropenia is estimated to affect approximately 1-4 people per million population in the United States.The congenital forms of severe chronic neutropenia are typically apparent in early infancy or during early childhood. Chronic idiopathic neutropenia usually affects adults but may present in early childhood.
|
Affects of Severe Chronic Neutropenia. Severe chronic neutropenia is a rare blood disorder that appears to affect females more than males in its idiopathic and autoimmune forms, with less discrepancy between the sexes in congenital forms. Both children and adults may be affected. Severe congenital neutropenia is estimated to affect approximately 1-4 people per million population in the United States.The congenital forms of severe chronic neutropenia are typically apparent in early infancy or during early childhood. Chronic idiopathic neutropenia usually affects adults but may present in early childhood.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_4
|
Related disorders of Severe Chronic Neutropenia
|
Symptoms of the following disorders may be similar to those of severe chronic neutropenia. Comparisons may be useful for a differential diagnosis.There are many different causes of neutropenia. Neutropenia may result from viral infection, use of certain drugs and/or certain nutritional deficiencies. Certain chemotherapeutic medications for the treatment of cancer cause predictable neutropenia. Neutropenia may also occur as a secondary finding due to other primary malignant or immunological disorders (e.g., leukemia, Hodgkin lymphoma, rheumatoid arthritis, inflammatory bowel disease, Sjogren's disease).Shwachman-Diamond syndrome is a rare genetic disorder with multiple and varied manifestations. The disorder is typically characterized by signs of insufficient absorption of fats and other nutrients due to abnormal function of the pancreas and improper functioning of the bone marrow, resulting in low levels of circulating blood cells (hematologic abnormalities), which can lead to severe chronic neutropenia. Additional characteristic findings may include short stature, abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis) and/or liver abnormalities.
|
Related disorders of Severe Chronic Neutropenia. Symptoms of the following disorders may be similar to those of severe chronic neutropenia. Comparisons may be useful for a differential diagnosis.There are many different causes of neutropenia. Neutropenia may result from viral infection, use of certain drugs and/or certain nutritional deficiencies. Certain chemotherapeutic medications for the treatment of cancer cause predictable neutropenia. Neutropenia may also occur as a secondary finding due to other primary malignant or immunological disorders (e.g., leukemia, Hodgkin lymphoma, rheumatoid arthritis, inflammatory bowel disease, Sjogren's disease).Shwachman-Diamond syndrome is a rare genetic disorder with multiple and varied manifestations. The disorder is typically characterized by signs of insufficient absorption of fats and other nutrients due to abnormal function of the pancreas and improper functioning of the bone marrow, resulting in low levels of circulating blood cells (hematologic abnormalities), which can lead to severe chronic neutropenia. Additional characteristic findings may include short stature, abnormal bone development affecting the rib cage and/or bones in the arms and/or legs (metaphyseal dysostosis) and/or liver abnormalities.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_5
|
Diagnosis of Severe Chronic Neutropenia
|
Severe chronic neutropenia can be diagnosed with a bone marrow aspirate, blood counts and genetic testing. The aspirate is collected after a detailed patient history, thorough clinical evaluation and blood tests (i.e., white blood cell count) that measure the various types of blood cells in the circulation. In individuals with severe chronic neutropenia, such blood counts demonstrate abnormally low levels of neutrophils. Normal counts of neutrophils range between 1.5 and 7 billion cells per liter of blood. If the neutrophil count falls below 0.5, then severe neutropenia is suggested. For diagnosing cyclic SCN, blood counts should be examined 3 times per week over two 21-day cycles or preferably by genetic testing for mutations in the ELANE gene.Autoimmune neutropenia may be tested for by measuring antibody levels to neutrophils, but these tests are not highly accurate, so a negative test result does not rule out the diagnosis. Positive antibody tests can also occur in congenital SCN. Clinical observations, bone marrow findings and genetic testing are gold standards for differentiating between congenital and autoimmune neutropenia. As there are many genetic causes of congenital neutropenia, it is most efficient and cost-effective to test a panel of possible genes rather than one at a time.
|
Diagnosis of Severe Chronic Neutropenia. Severe chronic neutropenia can be diagnosed with a bone marrow aspirate, blood counts and genetic testing. The aspirate is collected after a detailed patient history, thorough clinical evaluation and blood tests (i.e., white blood cell count) that measure the various types of blood cells in the circulation. In individuals with severe chronic neutropenia, such blood counts demonstrate abnormally low levels of neutrophils. Normal counts of neutrophils range between 1.5 and 7 billion cells per liter of blood. If the neutrophil count falls below 0.5, then severe neutropenia is suggested. For diagnosing cyclic SCN, blood counts should be examined 3 times per week over two 21-day cycles or preferably by genetic testing for mutations in the ELANE gene.Autoimmune neutropenia may be tested for by measuring antibody levels to neutrophils, but these tests are not highly accurate, so a negative test result does not rule out the diagnosis. Positive antibody tests can also occur in congenital SCN. Clinical observations, bone marrow findings and genetic testing are gold standards for differentiating between congenital and autoimmune neutropenia. As there are many genetic causes of congenital neutropenia, it is most efficient and cost-effective to test a panel of possible genes rather than one at a time.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1108_6
|
Therapies of Severe Chronic Neutropenia
|
TreatmentPrompt, appropriate treatment of infections associated with severe chronic neutropenia is essential. Such infections are usually managed with antibiotics. Even though patients have a normal immune response to viruses, good hygiene measures including avoiding crowds and adequate hand-washing are recommended to prevent secondary bacterial infections that can start after the immune system has been weakened from fighting off viral infections. Good dental hygiene, including regular dental exams, is required to prevent tooth loss.At the present time, the treatment of choice for SCN is the administration of granulocyte-colony stimulating factors (G-CSF). G-CSF is a manufactured version of the natural hormone that stimulates the bone marrow to produce neutrophils. G-CSF increases the number of neutrophils generated by the bone marrow and improves their bacteria-killing ability. It is recommended in patients with severe congenital neutropenia or with any form of SCN resulting in frequent infections and oral health problems. All forms of SCN have the potential to respond to G-CSF, and autoimmune forms respond better to G-CSF than immunosuppressive treatments used in other autoimmune diseases. In cyclic neutropenia, G-CSF shortens the number of days that neutrophil levels drop, and improves neutrophil levels at the low point, so that infections cannot develop. Side effects of G-CSF include headaches and bone, joint and muscle pain. Lower doses administered more frequently can lessen side effects. Prolonged use of G-CSF in congenital neutropenias has been associated with development of pre-leukemia or leukemia, but this complication is extremely rare in cyclic neutropenia and has not been reported in autoimmune or idiopathic neutropenias.Some affected individuals, mostly those with neutropenia due to systemic autoimmune diseases, such as lupus, may benefit from therapy with specific glucocorticoids, anti-inflammatory drugs that suppress the immune system. Glucocorticoids stimulate neutrophils to enter the blood stream from the bone marrow but don't acutally stimulate production of new neutrophils, and they might worsen neutrophil function. IVIG may also be helpful in autoimmune neutropenia but benefits are very short-lived and only about 50% of patients have a response to it. Typical immunosuppressant medications used in other autoimmune diseases, like methotrexate are not very effective in autoimmune neutropenia and are only tried if first-line treatment with G-CSF is not successful.Bone marrow transplantation has been used to treat patients with SCN and should be considered for any patient with severe congenital neutropenia with a matched sibling or 10/10-matched unrelated donor. Bone marrow transplants have the potential to cure SCN but bring additional risks into the management of the disorder. With bone marrow transplants, chemotherapy is administered to destroy existing bone marrow that is then replaced with bone marrow from a donor through an IV infusion. Genetic counseling is recommended for individuals with familial forms of severe chronic neutropenia and their families.
|
Therapies of Severe Chronic Neutropenia. TreatmentPrompt, appropriate treatment of infections associated with severe chronic neutropenia is essential. Such infections are usually managed with antibiotics. Even though patients have a normal immune response to viruses, good hygiene measures including avoiding crowds and adequate hand-washing are recommended to prevent secondary bacterial infections that can start after the immune system has been weakened from fighting off viral infections. Good dental hygiene, including regular dental exams, is required to prevent tooth loss.At the present time, the treatment of choice for SCN is the administration of granulocyte-colony stimulating factors (G-CSF). G-CSF is a manufactured version of the natural hormone that stimulates the bone marrow to produce neutrophils. G-CSF increases the number of neutrophils generated by the bone marrow and improves their bacteria-killing ability. It is recommended in patients with severe congenital neutropenia or with any form of SCN resulting in frequent infections and oral health problems. All forms of SCN have the potential to respond to G-CSF, and autoimmune forms respond better to G-CSF than immunosuppressive treatments used in other autoimmune diseases. In cyclic neutropenia, G-CSF shortens the number of days that neutrophil levels drop, and improves neutrophil levels at the low point, so that infections cannot develop. Side effects of G-CSF include headaches and bone, joint and muscle pain. Lower doses administered more frequently can lessen side effects. Prolonged use of G-CSF in congenital neutropenias has been associated with development of pre-leukemia or leukemia, but this complication is extremely rare in cyclic neutropenia and has not been reported in autoimmune or idiopathic neutropenias.Some affected individuals, mostly those with neutropenia due to systemic autoimmune diseases, such as lupus, may benefit from therapy with specific glucocorticoids, anti-inflammatory drugs that suppress the immune system. Glucocorticoids stimulate neutrophils to enter the blood stream from the bone marrow but don't acutally stimulate production of new neutrophils, and they might worsen neutrophil function. IVIG may also be helpful in autoimmune neutropenia but benefits are very short-lived and only about 50% of patients have a response to it. Typical immunosuppressant medications used in other autoimmune diseases, like methotrexate are not very effective in autoimmune neutropenia and are only tried if first-line treatment with G-CSF is not successful.Bone marrow transplantation has been used to treat patients with SCN and should be considered for any patient with severe congenital neutropenia with a matched sibling or 10/10-matched unrelated donor. Bone marrow transplants have the potential to cure SCN but bring additional risks into the management of the disorder. With bone marrow transplants, chemotherapy is administered to destroy existing bone marrow that is then replaced with bone marrow from a donor through an IV infusion. Genetic counseling is recommended for individuals with familial forms of severe chronic neutropenia and their families.
| 1,108 |
Severe Chronic Neutropenia
|
nord_1109_0
|
Overview of Severe Combined Immunodeficiency
|
Severe combined immunodeficiency (SCID) is a group of rare congenital syndromes with little or no immune responses. This results in frequent recurring infections with bacteria, fungi, and viruses. Infections that are minor in most people can be life‑threatening in people with SCID.The immune system includes specialized white blood cells that work together to fight off bacteria, fungi, and viruses. These white blood cells include T lymphocytes (T cells) that are central mediators of the immune response and also directly attack viruses. B lymphocytes (B cells) produce antibodies that attach to invaders and mark them to be destroyed, but they need T cells to work effectively. Natural killer (NK) cells are specialized to help fight viruses as well. Patients with SCID have a genetic defect that affects T cells and at least one other type of immune cell (hence “combined immunodeficiency”).Types of SCID are classified by which immune cells, T, B, and/or NK cells, are defective. There are several types of SCID, each caused by a different genetic (hereditary) defect. Despite the type of SCID, the primary symptom is reduced or absent immune function and all forms of classic SCID are lethal unless treated appropriately. The type of SCID helps determine the best treatment.Most states now have newborn screening for SCID to help detect and treat babies prior to them becoming sick. Early detection by newborn screening has dramatically increased the success of the bone marrow transplantation as babies with SCID can avoid early infections.
|
Overview of Severe Combined Immunodeficiency. Severe combined immunodeficiency (SCID) is a group of rare congenital syndromes with little or no immune responses. This results in frequent recurring infections with bacteria, fungi, and viruses. Infections that are minor in most people can be life‑threatening in people with SCID.The immune system includes specialized white blood cells that work together to fight off bacteria, fungi, and viruses. These white blood cells include T lymphocytes (T cells) that are central mediators of the immune response and also directly attack viruses. B lymphocytes (B cells) produce antibodies that attach to invaders and mark them to be destroyed, but they need T cells to work effectively. Natural killer (NK) cells are specialized to help fight viruses as well. Patients with SCID have a genetic defect that affects T cells and at least one other type of immune cell (hence “combined immunodeficiency”).Types of SCID are classified by which immune cells, T, B, and/or NK cells, are defective. There are several types of SCID, each caused by a different genetic (hereditary) defect. Despite the type of SCID, the primary symptom is reduced or absent immune function and all forms of classic SCID are lethal unless treated appropriately. The type of SCID helps determine the best treatment.Most states now have newborn screening for SCID to help detect and treat babies prior to them becoming sick. Early detection by newborn screening has dramatically increased the success of the bone marrow transplantation as babies with SCID can avoid early infections.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_1
|
Symptoms of Severe Combined Immunodeficiency
|
All newborn babies receive antibodies from their mothers during pregnancy that protect them from infections during the first few months of their lives. In the absence of family history of SCID and prior to newborn screening, babies with SCID often presented to medical attention between three and six months with severe infections as their maternal antibodies naturally decreased. Symptoms included rashes, diarrhea, recurrent infections, difficulty gaining weight, weakness and/or growth delay.Organisms that would cause mild to moderate illnesses in healthy people may cause life‑threatening infections in babies with SCID. Even organisms that do not ordinarily make people sick may make a child with SCID very ill. Babies with SCID typically suffer from many, severe cases of yeast (thrush or diaper rash), chicken pox, measles, herpes virus (cold sores), ear infections, meningitis (brain infections), or pneumonia that do not respond well to standard medical treatments. Children with SCID may also become infected with viruses (cytomegalovirus) from breastmilk, other live viruses (for example, the rotavirus or chickenpox) from vaccination or from common colds (viruses or bacteria) from siblings or surrounding children with healthy immune systems that can get rid of those infections.It is critical that a child with SCID receive a stem cell transplant as soon as possible and preferably in the first few months of life. Children with SCID should avoid any live vaccines, young children that can often transmit common infections, and breast feeding until the milk can be tested to ensure the best success of the bone marrow transplant.
|
Symptoms of Severe Combined Immunodeficiency. All newborn babies receive antibodies from their mothers during pregnancy that protect them from infections during the first few months of their lives. In the absence of family history of SCID and prior to newborn screening, babies with SCID often presented to medical attention between three and six months with severe infections as their maternal antibodies naturally decreased. Symptoms included rashes, diarrhea, recurrent infections, difficulty gaining weight, weakness and/or growth delay.Organisms that would cause mild to moderate illnesses in healthy people may cause life‑threatening infections in babies with SCID. Even organisms that do not ordinarily make people sick may make a child with SCID very ill. Babies with SCID typically suffer from many, severe cases of yeast (thrush or diaper rash), chicken pox, measles, herpes virus (cold sores), ear infections, meningitis (brain infections), or pneumonia that do not respond well to standard medical treatments. Children with SCID may also become infected with viruses (cytomegalovirus) from breastmilk, other live viruses (for example, the rotavirus or chickenpox) from vaccination or from common colds (viruses or bacteria) from siblings or surrounding children with healthy immune systems that can get rid of those infections.It is critical that a child with SCID receive a stem cell transplant as soon as possible and preferably in the first few months of life. Children with SCID should avoid any live vaccines, young children that can often transmit common infections, and breast feeding until the milk can be tested to ensure the best success of the bone marrow transplant.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_2
|
Causes of Severe Combined Immunodeficiency
|
Typical or Classic SCIDSCID may be inherited as an autosomal recessive genetic trait or an X-linked trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes: one received from the father and one from the mother.Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits 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 altered gene and 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 normal genes from both parents is 25%. The risk is the same for males and females.SCID can also be inherited as an X-linked disorder. X-linked genetic disorders are caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an altered gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. If a male with an X-linked disorder is able to reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Newborn babies with SCID develop similar symptoms including difficulty gaining weight, diarrhea and recurrent infections. There are four main categories of typical or classic SCID based upon which immune cells (T, B, or NK cells) are defective. The categories are most important for treatment considerations.B-positive, NK-negative severe combined immunodeficiency (T-B+NK- SCID)T-negative, B-positive, natural killer (NK)-negative (T-B+NK-) SCID is a type of SCID that occurs when T cells and NK cells cannot respond to growth factors (cytokines) needed to develop and survive in the body. The most common cause of T-B+NK- SCID, is X‑linked recessive SCID (X-SCID) caused by an altered IL2RG gene found on the X chromosome. The IL2RG gene codes for the protein gamma subunit (γc) of the cytokine receptors for interleukin (IL-)2, IL-4, IL-7, IL-9, IL-15, and IL-21. The γc receptor is defective in boys with X-SCID and cannot send signals from the growth factors needed to make functional T cells and NK cells. The B cells in these patients are also non-functional without the help from T cells.T-B+NK- SCID can also be caused by autosomal recessive mutations in the JAK3 gene. As in X-SCID, the T cells and NK cells in the body need the JAK3 protein to respond to the growth factors needed to develop and survive in the body. Defects in the JAK3 gene are now known to cause most autosomal recessive cases of T-B+NK- SCID.B-negative, NK-positive severe combined immunodeficiency (T-B-NK+ SCID)T-B-NK+ SCID is caused by a defect in both T and B cells, but not NK cells. The T cells and B cells in the body need both growth factors and expression of an antigen receptor to develop and survive. Each T cell or B cell recognizes a unique antigen (part of an invading bacteria, fungi or virus) through its particular antigen receptor. The cellular machinery needed to make a unique antigen receptor includes recombinase activating genes 1 (RAG1) and 2 (RAG2). Many mutations in RAG1 or RAG2 result in absent or non-functional protein causing T-B-NK+ SCID. If a mutation causes a reduced function the RAG1 or RAG2 proteins, then Atypical or Leaky SCID can occur (see below).Other rarer causes of T-B-NK+ SCID result from defects in other genes also needed to make the antigen receptor including DCLRE1C gene that encodes for Artemis protein, notably with a higher frequency in the southwestern Athabascan-speaking Native American population. Other radiation sensitive disorders caused by autosomal recessive genes (PRKDC, LIG4, NHEJ1) have been rarely reported to cause T-B-NK+ SCID as well. These are all autosomal recessive forms of SCID.B-negative, NK-negative severe combined immunodeficiency (T-B-NK- SCID)Adenosine deaminase deficiency is the most common cause of T-B-NK- SCID. ADA‑SCID, caused by an altered ADA gene, is autosomal recessive. Individuals with ADA‑SCID have no T, B, or NK cells and so tend to get bacterial, fungal, and viral diseases. There is some variation in when ADA-SCID patients develop symptoms depending upon the particular defect in the ADA gene. Some patients develop symptoms shortly after birth (early onset), and others later (delayed or late onset). Individuals with delayed ADA-SCID can be missed by the newborn screening test because they may have detectable numbers of lymphocytes. ADA functional testing is then needed to make the diagnosis.Another form of T-B-NK- SCID is caused by mutations in adenylate kinase 2 (AK2), a gene involved in the development of lymphocytes and other white blood cells in the bone marrow needed to fight infection. Defects in AK2 result in a severe form of SCID termed reticular dysgenesis and is usually accompanied by defects in hearing and low neutrophils as well. The profound neutropenia results in earlier risk for severe infections.B-positive, NK-positive severe combined immunodeficiency (T-B+NK+ SCID)Defects selective only to the T cells cause T-B+NK+ SCID and result from either loss of a cytokine (or growth factor) receptor or T cell antigen receptor, both needed for T cells to develop and survive. Deficiency of the alpha chain of the IL‑7 receptor (IL7R gene) is the most common form of this category of SCID. In humans, IL-7 is critical for the survival of T cells, but not B cells nor NK cells. Rarer defects in the components of the T cell antigen receptor have been reported to cause T-B+NK+ SCID including mutations in CD3D, CD3E, and CD247. In addition, PTPRC gene encodes a CD45 protein that is a critical regulator of the T cell antigen receptor. Several cases of mutations in PTPRC gene have been reported to cause T-B-NK+ SCID. All of these genes are autosomal recessive.Leaky SCID (also known as Omenn syndrome or atypical SCID)Some infants with SCID may have detectable or even elevated T cell numbers in a condition termed atypical or leaky SCID. These patients have only partial defects in known SCID-causing genes allowing for production of small numbers of T cells. These T cells do not provide protection from infections but are over-activated causing inflammation and damage similar to an autoimmune disease. Leaky SCID is the clinical syndrome that occurs with severe itchy rashes, enlarged lymph nodes, spleen and liver and chronic diarrhea. Typically leaky SCID is from partial function of either RAG1 or RAG2 genes, but has been reported in other forms of SCID as well. Importantly, leaky SCID must be distinguished from engraftment of maternal T cells that can cross the placental during pregnancy or delivery and in the absence of fetal T cells can persist in the baby after birth. These cells can be destructive to the infant and cause similar symptoms further complicating the diagnosis.Variant SCID (persistently low T-cells but no defect in known SCID genes)The rise of newborn screening has increased the detection of infants with persistently low T-cells with no known defect in a known SCID gene. These children require special considerations for further work up and management and may represent a combined immunodeficiency or SCID-like disorder.
|
Causes of Severe Combined Immunodeficiency. Typical or Classic SCIDSCID may be inherited as an autosomal recessive genetic trait or an X-linked trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes: one received from the father and one from the mother.Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits 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 altered gene and 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 normal genes from both parents is 25%. The risk is the same for males and females.SCID can also be inherited as an X-linked disorder. X-linked genetic disorders are caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have an altered gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains an altered gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son. If a male with an X-linked disorder is able to reproduce, he will pass the altered gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Newborn babies with SCID develop similar symptoms including difficulty gaining weight, diarrhea and recurrent infections. There are four main categories of typical or classic SCID based upon which immune cells (T, B, or NK cells) are defective. The categories are most important for treatment considerations.B-positive, NK-negative severe combined immunodeficiency (T-B+NK- SCID)T-negative, B-positive, natural killer (NK)-negative (T-B+NK-) SCID is a type of SCID that occurs when T cells and NK cells cannot respond to growth factors (cytokines) needed to develop and survive in the body. The most common cause of T-B+NK- SCID, is X‑linked recessive SCID (X-SCID) caused by an altered IL2RG gene found on the X chromosome. The IL2RG gene codes for the protein gamma subunit (γc) of the cytokine receptors for interleukin (IL-)2, IL-4, IL-7, IL-9, IL-15, and IL-21. The γc receptor is defective in boys with X-SCID and cannot send signals from the growth factors needed to make functional T cells and NK cells. The B cells in these patients are also non-functional without the help from T cells.T-B+NK- SCID can also be caused by autosomal recessive mutations in the JAK3 gene. As in X-SCID, the T cells and NK cells in the body need the JAK3 protein to respond to the growth factors needed to develop and survive in the body. Defects in the JAK3 gene are now known to cause most autosomal recessive cases of T-B+NK- SCID.B-negative, NK-positive severe combined immunodeficiency (T-B-NK+ SCID)T-B-NK+ SCID is caused by a defect in both T and B cells, but not NK cells. The T cells and B cells in the body need both growth factors and expression of an antigen receptor to develop and survive. Each T cell or B cell recognizes a unique antigen (part of an invading bacteria, fungi or virus) through its particular antigen receptor. The cellular machinery needed to make a unique antigen receptor includes recombinase activating genes 1 (RAG1) and 2 (RAG2). Many mutations in RAG1 or RAG2 result in absent or non-functional protein causing T-B-NK+ SCID. If a mutation causes a reduced function the RAG1 or RAG2 proteins, then Atypical or Leaky SCID can occur (see below).Other rarer causes of T-B-NK+ SCID result from defects in other genes also needed to make the antigen receptor including DCLRE1C gene that encodes for Artemis protein, notably with a higher frequency in the southwestern Athabascan-speaking Native American population. Other radiation sensitive disorders caused by autosomal recessive genes (PRKDC, LIG4, NHEJ1) have been rarely reported to cause T-B-NK+ SCID as well. These are all autosomal recessive forms of SCID.B-negative, NK-negative severe combined immunodeficiency (T-B-NK- SCID)Adenosine deaminase deficiency is the most common cause of T-B-NK- SCID. ADA‑SCID, caused by an altered ADA gene, is autosomal recessive. Individuals with ADA‑SCID have no T, B, or NK cells and so tend to get bacterial, fungal, and viral diseases. There is some variation in when ADA-SCID patients develop symptoms depending upon the particular defect in the ADA gene. Some patients develop symptoms shortly after birth (early onset), and others later (delayed or late onset). Individuals with delayed ADA-SCID can be missed by the newborn screening test because they may have detectable numbers of lymphocytes. ADA functional testing is then needed to make the diagnosis.Another form of T-B-NK- SCID is caused by mutations in adenylate kinase 2 (AK2), a gene involved in the development of lymphocytes and other white blood cells in the bone marrow needed to fight infection. Defects in AK2 result in a severe form of SCID termed reticular dysgenesis and is usually accompanied by defects in hearing and low neutrophils as well. The profound neutropenia results in earlier risk for severe infections.B-positive, NK-positive severe combined immunodeficiency (T-B+NK+ SCID)Defects selective only to the T cells cause T-B+NK+ SCID and result from either loss of a cytokine (or growth factor) receptor or T cell antigen receptor, both needed for T cells to develop and survive. Deficiency of the alpha chain of the IL‑7 receptor (IL7R gene) is the most common form of this category of SCID. In humans, IL-7 is critical for the survival of T cells, but not B cells nor NK cells. Rarer defects in the components of the T cell antigen receptor have been reported to cause T-B+NK+ SCID including mutations in CD3D, CD3E, and CD247. In addition, PTPRC gene encodes a CD45 protein that is a critical regulator of the T cell antigen receptor. Several cases of mutations in PTPRC gene have been reported to cause T-B-NK+ SCID. All of these genes are autosomal recessive.Leaky SCID (also known as Omenn syndrome or atypical SCID)Some infants with SCID may have detectable or even elevated T cell numbers in a condition termed atypical or leaky SCID. These patients have only partial defects in known SCID-causing genes allowing for production of small numbers of T cells. These T cells do not provide protection from infections but are over-activated causing inflammation and damage similar to an autoimmune disease. Leaky SCID is the clinical syndrome that occurs with severe itchy rashes, enlarged lymph nodes, spleen and liver and chronic diarrhea. Typically leaky SCID is from partial function of either RAG1 or RAG2 genes, but has been reported in other forms of SCID as well. Importantly, leaky SCID must be distinguished from engraftment of maternal T cells that can cross the placental during pregnancy or delivery and in the absence of fetal T cells can persist in the baby after birth. These cells can be destructive to the infant and cause similar symptoms further complicating the diagnosis.Variant SCID (persistently low T-cells but no defect in known SCID genes)The rise of newborn screening has increased the detection of infants with persistently low T-cells with no known defect in a known SCID gene. These children require special considerations for further work up and management and may represent a combined immunodeficiency or SCID-like disorder.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_3
|
Affects of Severe Combined Immunodeficiency
|
All types of SCID are very rare disorders that occur in approximately 1 or fewer births in 100,000 in the United States. SCID may be more common in people with Navajo, Apache, or Turkish ancestry.
|
Affects of Severe Combined Immunodeficiency. All types of SCID are very rare disorders that occur in approximately 1 or fewer births in 100,000 in the United States. SCID may be more common in people with Navajo, Apache, or Turkish ancestry.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_4
|
Related disorders of Severe Combined Immunodeficiency
|
Symptoms of the following disorders can be similar to those of SCID. Comparisons may be useful for a differential diagnosis:
|
Related disorders of Severe Combined Immunodeficiency. Symptoms of the following disorders can be similar to those of SCID. Comparisons may be useful for a differential diagnosis:
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_5
|
Diagnosis of Severe Combined Immunodeficiency
|
SCID is now diagnosed mainly through from newborn screening in most states. The screen is performed using the dried blood spot from newborn screening (or Guthrie) cards measuring levels T-cell receptor excision circles (or TREC). Although each state has a slightly different methods and thresholds, a low TREC test means the infant has low numbers of lymphocytes in the blood at the time of the test. The result must then be confirmed with additional testing. A complete blood count (CBC) coupled with lymphocyte subset testing may show low levels of B, T, and/or NK cells. Additional tests can show that one or more of these cell types aren’t functioning properly. Genetic and biochemical (protein expression) tests are available for some forms of SCID. A combination of these tests may be required to make an accurate diagnosis needed to plan treatment.
|
Diagnosis of Severe Combined Immunodeficiency. SCID is now diagnosed mainly through from newborn screening in most states. The screen is performed using the dried blood spot from newborn screening (or Guthrie) cards measuring levels T-cell receptor excision circles (or TREC). Although each state has a slightly different methods and thresholds, a low TREC test means the infant has low numbers of lymphocytes in the blood at the time of the test. The result must then be confirmed with additional testing. A complete blood count (CBC) coupled with lymphocyte subset testing may show low levels of B, T, and/or NK cells. Additional tests can show that one or more of these cell types aren’t functioning properly. Genetic and biochemical (protein expression) tests are available for some forms of SCID. A combination of these tests may be required to make an accurate diagnosis needed to plan treatment.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1109_6
|
Therapies of Severe Combined Immunodeficiency
|
Treatment
Transplant of stem cells taken from the bone marrow of a healthy, matching donor, usually by the age of about 3 months, is generally considered the best treatment for SCID. A bone marrow transplantation center is needed to evaluate the patient for potential matching donors through national searches, determine the options for each patient and explain the risks of each treatment option. The type of SCID and the bone marrow match available to the patient are both two important considerations. While waiting for a bone marrow transplant, avoiding sick contacts and avoiding breast feeding is critical to prevent transmission of infections that can make a transplant less successful. If diagnosis is delayed and infections occur, they must be treated aggressively. Gene therapy for SCID is still considered to be experimental (investigational), but considered in patients not eligible for a bone marrow transplant.An enzyme replacement therapy, where a missing enzyme is injected regularly into the patient, is available for ADA SCID. This is a treatment, not a cure. Transplant of stem cells from the bone marrow of a healthy, matching, donor is the only cure for SCID currently.An enzyme replacement therapy, where a missing enzyme is injected regularly into the patient, is available for ADA SCID. This is a treatment, not a cure. Transplant of stem cells from the bone marrow of a healthy, matching, donor is the only cure for SCID currently.In 2018, the enzyme replacement therapy Revcovi (elapegademase-lvlr) was approved for the treatment of ADA-SCID in pediatric and adult patients. Revcovi is manufactured by Leadiant Biosciences.
|
Therapies of Severe Combined Immunodeficiency. Treatment
Transplant of stem cells taken from the bone marrow of a healthy, matching donor, usually by the age of about 3 months, is generally considered the best treatment for SCID. A bone marrow transplantation center is needed to evaluate the patient for potential matching donors through national searches, determine the options for each patient and explain the risks of each treatment option. The type of SCID and the bone marrow match available to the patient are both two important considerations. While waiting for a bone marrow transplant, avoiding sick contacts and avoiding breast feeding is critical to prevent transmission of infections that can make a transplant less successful. If diagnosis is delayed and infections occur, they must be treated aggressively. Gene therapy for SCID is still considered to be experimental (investigational), but considered in patients not eligible for a bone marrow transplant.An enzyme replacement therapy, where a missing enzyme is injected regularly into the patient, is available for ADA SCID. This is a treatment, not a cure. Transplant of stem cells from the bone marrow of a healthy, matching, donor is the only cure for SCID currently.An enzyme replacement therapy, where a missing enzyme is injected regularly into the patient, is available for ADA SCID. This is a treatment, not a cure. Transplant of stem cells from the bone marrow of a healthy, matching, donor is the only cure for SCID currently.In 2018, the enzyme replacement therapy Revcovi (elapegademase-lvlr) was approved for the treatment of ADA-SCID in pediatric and adult patients. Revcovi is manufactured by Leadiant Biosciences.
| 1,109 |
Severe Combined Immunodeficiency
|
nord_1110_0
|
Overview of Shashi-Pena Syndrome
|
SummaryShashi-Pena syndrome is a rare multiple malformation syndrome that presents at birth with characteristic facial features, enlarged head circumference and other characteristic findings such as a birthmark above the bridge of the nose (glabellar nevus flammeus), along with low muscle tone and global developmental delay. Certain features such as epilepsy occur in some affected individuals, but not all. The condition is caused by changes (mutations) in the ASXL2 gene that have occurred as new mutations (de novo) in affected individuals. The condition is thought to follow an autosomal dominant pattern of inheritance. Treatment is targeted to the individual symptoms, and consists of supportive care for the complications, such as cardiology follow up in case of congenital heart disease and developmental therapies.IntroductionShashi-Pena syndrome was initially described in 2016 by Dr. Vandana Shashi and Dr. Loren Pena in a group of six children who had overlapping facial features and clinical findings. The physical findings were most prominent in the first few years of life. The ASXL2 gene had not previously been associated with a disease in humans.
|
Overview of Shashi-Pena Syndrome. SummaryShashi-Pena syndrome is a rare multiple malformation syndrome that presents at birth with characteristic facial features, enlarged head circumference and other characteristic findings such as a birthmark above the bridge of the nose (glabellar nevus flammeus), along with low muscle tone and global developmental delay. Certain features such as epilepsy occur in some affected individuals, but not all. The condition is caused by changes (mutations) in the ASXL2 gene that have occurred as new mutations (de novo) in affected individuals. The condition is thought to follow an autosomal dominant pattern of inheritance. Treatment is targeted to the individual symptoms, and consists of supportive care for the complications, such as cardiology follow up in case of congenital heart disease and developmental therapies.IntroductionShashi-Pena syndrome was initially described in 2016 by Dr. Vandana Shashi and Dr. Loren Pena in a group of six children who had overlapping facial features and clinical findings. The physical findings were most prominent in the first few years of life. The ASXL2 gene had not previously been associated with a disease in humans.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1110_1
|
Symptoms of Shashi-Pena Syndrome
|
Patients affected with Shashi-Pena syndrome have low muscle tone (hypotonia) and a characteristic facial appearance consisting of wide-set eyes (hypertelorism) that are also prominent, droopy eyelids (ptosis), a red or pink birthmark above the bridge of the nose (glabellar nevus flammeus), low set and posteriorly rotated ears and enlarged head size (macrocephaly). Feeding difficulties early in life are common. Some children have low blood sugar (hypoglycemia) early in life, and rarely this can become a persistent complication. The early hypotonia can evolve into subsequent delays in gross motor skills that manifest as delayed walking. There is also a delay in speech and behavioral problems that can include attention deficit and autistic features. Some patients have capillary malformations in addition to the glabellar nevus flammeus, skeletal abnormalities such as an advanced bone age, curvature of the spine (scoliosis and kyphosis) and congenital heart defects such as atrial septal defects. Some patients may have seizures while having a fever and epilepsy may sometimes develop. Several patients have had brain abnormalities consisting of enlarged ventricles and loss of cerebral white matter.
|
Symptoms of Shashi-Pena Syndrome. Patients affected with Shashi-Pena syndrome have low muscle tone (hypotonia) and a characteristic facial appearance consisting of wide-set eyes (hypertelorism) that are also prominent, droopy eyelids (ptosis), a red or pink birthmark above the bridge of the nose (glabellar nevus flammeus), low set and posteriorly rotated ears and enlarged head size (macrocephaly). Feeding difficulties early in life are common. Some children have low blood sugar (hypoglycemia) early in life, and rarely this can become a persistent complication. The early hypotonia can evolve into subsequent delays in gross motor skills that manifest as delayed walking. There is also a delay in speech and behavioral problems that can include attention deficit and autistic features. Some patients have capillary malformations in addition to the glabellar nevus flammeus, skeletal abnormalities such as an advanced bone age, curvature of the spine (scoliosis and kyphosis) and congenital heart defects such as atrial septal defects. Some patients may have seizures while having a fever and epilepsy may sometimes develop. Several patients have had brain abnormalities consisting of enlarged ventricles and loss of cerebral white matter.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1110_2
|
Causes of Shashi-Pena Syndrome
|
Shashi-Pena syndrome is caused mutations in the ASXL2 gene. The function of the ASXL2 gene is not known to date, but may have a role in regulating gene expression during embryological development. The specific type of mutation observed in affected individuals is called a premature truncation. This means that the protein produced by the gene is shorter than it would typically be. This abnormal protein may lead to the abnormalities in the body that are seen in this condition.The ASXL2 gene mutations are new (de novo) in all of the individuals published to date. This means that neither parent has the mutation. The condition is thought to be inherited in an autosomal dominant manner, although no affected individual is known to have reproduced. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The risk of passing the non-working gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
|
Causes of Shashi-Pena Syndrome. Shashi-Pena syndrome is caused mutations in the ASXL2 gene. The function of the ASXL2 gene is not known to date, but may have a role in regulating gene expression during embryological development. The specific type of mutation observed in affected individuals is called a premature truncation. This means that the protein produced by the gene is shorter than it would typically be. This abnormal protein may lead to the abnormalities in the body that are seen in this condition.The ASXL2 gene mutations are new (de novo) in all of the individuals published to date. This means that neither parent has the mutation. The condition is thought to be inherited in an autosomal dominant manner, although no affected individual is known to have reproduced. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The risk of passing the non-working gene from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1110_3
|
Affects of Shashi-Pena Syndrome
|
The disorder has been described in a variety of populations, without preference for a specific race or ethnicity. The prevalence and incidence of Shashi -Pena syndrome are unknown.
|
Affects of Shashi-Pena Syndrome. The disorder has been described in a variety of populations, without preference for a specific race or ethnicity. The prevalence and incidence of Shashi -Pena syndrome are unknown.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1110_4
|
Related disorders of Shashi-Pena Syndrome
|
Related disorders of Shashi-Pena Syndrome.
| 1,110 |
Shashi-Pena Syndrome
|
|
nord_1110_5
|
Diagnosis of Shashi-Pena Syndrome
|
The condition is diagnosed by DNA-based testing to look for mutations in the ASXL2 gene.
|
Diagnosis of Shashi-Pena Syndrome. The condition is diagnosed by DNA-based testing to look for mutations in the ASXL2 gene.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1110_6
|
Therapies of Shashi-Pena Syndrome
|
Treatment
Supportive treatment is geared towards the known complications associated with this syndrome. This could include developmental therapies, cardiology surveillance for congenital heart disease, neurology evaluation and management in case of seizures, feeding evaluation if feeding difficulties and low blood sugar (hypoglycemia) are present. There are currently no approved therapies. Follow up includes a multidisciplinary approach with specialists in these areas: genetics, neurology, cardiology, endocrinology, physical and occupational therapy, feeding and speech therapy.
|
Therapies of Shashi-Pena Syndrome. Treatment
Supportive treatment is geared towards the known complications associated with this syndrome. This could include developmental therapies, cardiology surveillance for congenital heart disease, neurology evaluation and management in case of seizures, feeding evaluation if feeding difficulties and low blood sugar (hypoglycemia) are present. There are currently no approved therapies. Follow up includes a multidisciplinary approach with specialists in these areas: genetics, neurology, cardiology, endocrinology, physical and occupational therapy, feeding and speech therapy.
| 1,110 |
Shashi-Pena Syndrome
|
nord_1111_0
|
Overview of Sheehan Syndrome
|
Excessive blood loss during or after delivery of a baby may affect the function of the pituitary gland, leading to a form of maternal hypopituitarism known as Sheehan syndrome (SS). Such extensive bleeding may reduce the blood flow to the pituitary gland causing the pituitary cells to be damaged or die (necrosis). Thus, the production of the usual pituitary hormones will be reduced, perhaps by a significant amount. During pregnancy the pituitary gland will enlarge and may double in size. At this time the gland is especially vulnerable to a severe drop in blood pressure (sometimes called “shock”) and excessive maternal bleeding may induce the “shock” and the damage to the cells of the gland. At that time the amount of hormones produced by the pituitary may be decreased giving rise to the symptoms associated with hypopituitarism. There appear to be two forms of the disorder: a chronic form and an acute form, depending on the amount of damage to the gland’s cells. The acute form reflects considerable damage so that symptoms become apparent soon after delivery. In chronic cases, the volume of damage is much less, and symptoms may not appear for months or years after delivery.
|
Overview of Sheehan Syndrome. Excessive blood loss during or after delivery of a baby may affect the function of the pituitary gland, leading to a form of maternal hypopituitarism known as Sheehan syndrome (SS). Such extensive bleeding may reduce the blood flow to the pituitary gland causing the pituitary cells to be damaged or die (necrosis). Thus, the production of the usual pituitary hormones will be reduced, perhaps by a significant amount. During pregnancy the pituitary gland will enlarge and may double in size. At this time the gland is especially vulnerable to a severe drop in blood pressure (sometimes called “shock”) and excessive maternal bleeding may induce the “shock” and the damage to the cells of the gland. At that time the amount of hormones produced by the pituitary may be decreased giving rise to the symptoms associated with hypopituitarism. There appear to be two forms of the disorder: a chronic form and an acute form, depending on the amount of damage to the gland’s cells. The acute form reflects considerable damage so that symptoms become apparent soon after delivery. In chronic cases, the volume of damage is much less, and symptoms may not appear for months or years after delivery.
| 1,111 |
Sheehan Syndrome
|
nord_1111_1
|
Symptoms of Sheehan Syndrome
|
The clinical features of Sheehan syndrome are highly variable and depend on the degree of failure of secretion of pituitary hormones including:• Prolactin, the hormone that stimulates lactation
• Gonadotrophins (luteinizing hormone [LH] and follicle stimulating hormone [FSH]), which regulate the function of the ovaries
• TSH, which stimulates the thyroid gland
• ACTH, adrenocorticotrophin, which stimulates the adrenal cortex
• Growth hormone (GH)How much pituitary tissue is killed, and by how much the hormone levels in the circulation are decreased, determine what happens to the mother. Patients with the chronic form have a smaller proportion of the pituitary tissue damaged and may not develop symptoms until weeks or even years after the birth.In its most severe form, the condition is associated with failure of lactation after a woman has a baby. Menstruation does not begin again, sexual interest (libido) is diminished, hair in the armpits (axilla) slowly disappears, breasts diminish in size (atrophy) and the lining of the vagina thins, sometimes causing pain with intercourse. For some women, menstrual periods do recur, and subsequent pregnancies have been reported.The characteristic symptoms (fatigue, dry skin, constipation, weight gain, sluggishness) of hypothyroidism usually develop gradually. Severe ACTH deficiency is associated with fatigue, chronic hypotension with fainting, and the inability to respond to stress. If these symptoms occur, they usually appear within weeks or months after the baby is born.
Since SS is a disorder affecting adults, the effects of growth hormone deficiency are limited to some loss of muscle strength, increased body fat and increased insulin sensitivity.The less common acute or more severe form is potentially very dangerous. In these cases, less than 10 percent of the normal volume of pituitary tissue remains. Patients may present with persistent low blood pressure (hypotension), irregular and fast heartbeat (tachycardia), as well as failure to lactate and low blood sugar (hypoglycemia) immediately following delivery.In both the chronic and acute forms, there may be signs of diabetes insipidus (DI) such as abnormal thirst for and intake of water, as well as high volume of output of urine.
|
Symptoms of Sheehan Syndrome. The clinical features of Sheehan syndrome are highly variable and depend on the degree of failure of secretion of pituitary hormones including:• Prolactin, the hormone that stimulates lactation
• Gonadotrophins (luteinizing hormone [LH] and follicle stimulating hormone [FSH]), which regulate the function of the ovaries
• TSH, which stimulates the thyroid gland
• ACTH, adrenocorticotrophin, which stimulates the adrenal cortex
• Growth hormone (GH)How much pituitary tissue is killed, and by how much the hormone levels in the circulation are decreased, determine what happens to the mother. Patients with the chronic form have a smaller proportion of the pituitary tissue damaged and may not develop symptoms until weeks or even years after the birth.In its most severe form, the condition is associated with failure of lactation after a woman has a baby. Menstruation does not begin again, sexual interest (libido) is diminished, hair in the armpits (axilla) slowly disappears, breasts diminish in size (atrophy) and the lining of the vagina thins, sometimes causing pain with intercourse. For some women, menstrual periods do recur, and subsequent pregnancies have been reported.The characteristic symptoms (fatigue, dry skin, constipation, weight gain, sluggishness) of hypothyroidism usually develop gradually. Severe ACTH deficiency is associated with fatigue, chronic hypotension with fainting, and the inability to respond to stress. If these symptoms occur, they usually appear within weeks or months after the baby is born.
Since SS is a disorder affecting adults, the effects of growth hormone deficiency are limited to some loss of muscle strength, increased body fat and increased insulin sensitivity.The less common acute or more severe form is potentially very dangerous. In these cases, less than 10 percent of the normal volume of pituitary tissue remains. Patients may present with persistent low blood pressure (hypotension), irregular and fast heartbeat (tachycardia), as well as failure to lactate and low blood sugar (hypoglycemia) immediately following delivery.In both the chronic and acute forms, there may be signs of diabetes insipidus (DI) such as abnormal thirst for and intake of water, as well as high volume of output of urine.
| 1,111 |
Sheehan Syndrome
|
nord_1111_2
|
Causes of Sheehan Syndrome
|
In most instances, a precipitous drop in blood pressure and consequent shock, due to obstetrical bleeding, precede the onset of symptoms. According to many physicians the amount of damage that must be done to the anterior pituitary before Sheehan syndrome occurs varies from 75 to 90 percent. The enlarged pituitary requires more than normal volumes of oxygen, and any disruption of blood flow is a threat to the gland.A severe spasm of the blood vessels feeding the pituitary (associated with shock) leads to lack of oxygen in the pituitary (pituitary ischemia) and various degrees of cellular damage depending on the severity and duration of arteriolar spasm.Pituitary necrosis is found in association with other disorders but far less frequently. These disorders include sickle cell anemia, giant cell arteritis and a couple of others including trauma.
|
Causes of Sheehan Syndrome. In most instances, a precipitous drop in blood pressure and consequent shock, due to obstetrical bleeding, precede the onset of symptoms. According to many physicians the amount of damage that must be done to the anterior pituitary before Sheehan syndrome occurs varies from 75 to 90 percent. The enlarged pituitary requires more than normal volumes of oxygen, and any disruption of blood flow is a threat to the gland.A severe spasm of the blood vessels feeding the pituitary (associated with shock) leads to lack of oxygen in the pituitary (pituitary ischemia) and various degrees of cellular damage depending on the severity and duration of arteriolar spasm.Pituitary necrosis is found in association with other disorders but far less frequently. These disorders include sickle cell anemia, giant cell arteritis and a couple of others including trauma.
| 1,111 |
Sheehan Syndrome
|
nord_1111_3
|
Affects of Sheehan Syndrome
|
Sheehan syndrome affects women with excessive blood loss and circulatory collapse following childbirth. The incidence of Sheehan syndrome is not known.
|
Affects of Sheehan Syndrome. Sheehan syndrome affects women with excessive blood loss and circulatory collapse following childbirth. The incidence of Sheehan syndrome is not known.
| 1,111 |
Sheehan Syndrome
|
nord_1111_4
|
Related disorders of Sheehan Syndrome
|
Antiphospholipid syndrome (APLS) is a rare autoimmune disorder characterized by recurring blood clots that usually appear before 45 years of age. It may also be associated with repeated spontaneous abortions for no apparent reason in young women. There may be a family history of blood clotting disorders in some cases. APLS may occur in individuals with lupus or related autoimmune diseases or as a primary syndrome in otherwise healthy individuals. (For more information on this condition, search for “APLS” in the Rare Disease Database.)Hypophysitis means inflammation of the pituitary gland. The irritation caused by the inflammatory reaction may interfere with the production of one or several of the pituitary hormones and in this respect hypophysitis may mimic, to some degree, the symptoms of Sheehan syndrome. Similarly, lesions of the pituitary gland such as pituitary adenomas, may also mimic Sheehan syndrome.
|
Related disorders of Sheehan Syndrome. Antiphospholipid syndrome (APLS) is a rare autoimmune disorder characterized by recurring blood clots that usually appear before 45 years of age. It may also be associated with repeated spontaneous abortions for no apparent reason in young women. There may be a family history of blood clotting disorders in some cases. APLS may occur in individuals with lupus or related autoimmune diseases or as a primary syndrome in otherwise healthy individuals. (For more information on this condition, search for “APLS” in the Rare Disease Database.)Hypophysitis means inflammation of the pituitary gland. The irritation caused by the inflammatory reaction may interfere with the production of one or several of the pituitary hormones and in this respect hypophysitis may mimic, to some degree, the symptoms of Sheehan syndrome. Similarly, lesions of the pituitary gland such as pituitary adenomas, may also mimic Sheehan syndrome.
| 1,111 |
Sheehan Syndrome
|
nord_1111_5
|
Diagnosis of Sheehan Syndrome
|
In patients with severe hemorrhaging on delivery accompanied by long-lasting low blood pressure, treatment is started as soon as possible. Women believed to have the chronic form usually have blood drawn and the levels for several hormones are determined. Often, a head computed tomography (CT) or magnetic resonance imaging (MRI) scan is done; acutely this will usually show hemorrhage in the pituitary but chronically, as the blood resolves, this will show just a diminished size of the pituitary.
|
Diagnosis of Sheehan Syndrome. In patients with severe hemorrhaging on delivery accompanied by long-lasting low blood pressure, treatment is started as soon as possible. Women believed to have the chronic form usually have blood drawn and the levels for several hormones are determined. Often, a head computed tomography (CT) or magnetic resonance imaging (MRI) scan is done; acutely this will usually show hemorrhage in the pituitary but chronically, as the blood resolves, this will show just a diminished size of the pituitary.
| 1,111 |
Sheehan Syndrome
|
nord_1111_6
|
Therapies of Sheehan Syndrome
|
TreatmentTreatment of Sheehan syndrome consists of hormone replacement, i.e., ovarian, thyroid, and adrenocortical hormones (ACTH). Since in most cases ACTH deficiency is only partial, continuing cortisol replacement therapy may not be required. Hydrocortisone or prednisone are generally used to replace ACTH and cortisol; thyroxine replaces thyroid hormone; estrogen/progesterone replacement is usually achieved by administering oral contraceptives, while any indication of diabetes insipidus requires the use of demopressin. Growth hormone (GH) replacement therapy has been approved by the U.S. Food and Drug Administration (FDA) for adults with documented GH deficiency. Its use in cases of Sheehan syndrome should be monitored and managed by a physician experienced in using GH. Benefits include increased muscle mass, reduction in the low-density lipoproteins and an enhanced sense of well-being.Information on replacement therapy in cases of hypopituitarism is readily available from:The Pituitary Foundation
http://www.pituitary.org.ukThe Hormone Foundation
http://www.hormone.org
|
Therapies of Sheehan Syndrome. TreatmentTreatment of Sheehan syndrome consists of hormone replacement, i.e., ovarian, thyroid, and adrenocortical hormones (ACTH). Since in most cases ACTH deficiency is only partial, continuing cortisol replacement therapy may not be required. Hydrocortisone or prednisone are generally used to replace ACTH and cortisol; thyroxine replaces thyroid hormone; estrogen/progesterone replacement is usually achieved by administering oral contraceptives, while any indication of diabetes insipidus requires the use of demopressin. Growth hormone (GH) replacement therapy has been approved by the U.S. Food and Drug Administration (FDA) for adults with documented GH deficiency. Its use in cases of Sheehan syndrome should be monitored and managed by a physician experienced in using GH. Benefits include increased muscle mass, reduction in the low-density lipoproteins and an enhanced sense of well-being.Information on replacement therapy in cases of hypopituitarism is readily available from:The Pituitary Foundation
http://www.pituitary.org.ukThe Hormone Foundation
http://www.hormone.org
| 1,111 |
Sheehan Syndrome
|
nord_1112_0
|
Overview of Short Bowel Syndrome
|
SummaryShort bowel syndrome is a complex disease that occurs due to the physical loss or the loss of function of a portion of the small and/or large intestine. Consequently, individuals with short bowel syndrome often have a reduced ability to absorb nutrients such as fats, carbohydrates (sugars) vitamins, minerals, trace elements and fluids (malabsorption). The specific symptoms and severity of short bowel syndrome vary from one person to another. Diarrhea is common, often severe and can cause dehydration, which can even be life threatening. Short bowel syndrome can lead to malnutrition, unintended weight loss and additional symptoms may be due to the loss of essential vitamins and minerals. There is no cure, but the disorder usually can be treated effectively. However, in some cases, short bowel syndrome can lead to severe, disabling and life-threatening complications. Short bowel syndrome is most commonly associated with the surgical removal (resection) of half or more of the small intestine. Such surgery is performed to treat intestinal diseases such as Crohn's disease, injury or trauma to the small bowel, or congenital birth defects. The presence or absence of the large intestine (colon) also plays an important role in the genesis and/or treatment of the short bowel syndrome.IntroductionThrough the years, the definition of short bowel syndrome in the medical literature has varied. This has led to confusion. Although some medical sources seem to reserve the name short bowel syndrome for cases caused by surgical resection of a portion of the small intestine, other sources have noted that the disorder can result from any disease, injury or condition that hinders or prevents the proper function of the small intestine even if the length of the bowel is unaffected. Short bowel syndrome may be classified as a cause or subcategory of intestinal failure. In rare cases, infants are born with a short bowel (congenital short bowel syndrome). Although these congenital cases are often associated with malrotation of the small intestine, the exact cause of congenital short bowel syndrome is unknown.
|
Overview of Short Bowel Syndrome. SummaryShort bowel syndrome is a complex disease that occurs due to the physical loss or the loss of function of a portion of the small and/or large intestine. Consequently, individuals with short bowel syndrome often have a reduced ability to absorb nutrients such as fats, carbohydrates (sugars) vitamins, minerals, trace elements and fluids (malabsorption). The specific symptoms and severity of short bowel syndrome vary from one person to another. Diarrhea is common, often severe and can cause dehydration, which can even be life threatening. Short bowel syndrome can lead to malnutrition, unintended weight loss and additional symptoms may be due to the loss of essential vitamins and minerals. There is no cure, but the disorder usually can be treated effectively. However, in some cases, short bowel syndrome can lead to severe, disabling and life-threatening complications. Short bowel syndrome is most commonly associated with the surgical removal (resection) of half or more of the small intestine. Such surgery is performed to treat intestinal diseases such as Crohn's disease, injury or trauma to the small bowel, or congenital birth defects. The presence or absence of the large intestine (colon) also plays an important role in the genesis and/or treatment of the short bowel syndrome.IntroductionThrough the years, the definition of short bowel syndrome in the medical literature has varied. This has led to confusion. Although some medical sources seem to reserve the name short bowel syndrome for cases caused by surgical resection of a portion of the small intestine, other sources have noted that the disorder can result from any disease, injury or condition that hinders or prevents the proper function of the small intestine even if the length of the bowel is unaffected. Short bowel syndrome may be classified as a cause or subcategory of intestinal failure. In rare cases, infants are born with a short bowel (congenital short bowel syndrome). Although these congenital cases are often associated with malrotation of the small intestine, the exact cause of congenital short bowel syndrome is unknown.
| 1,112 |
Short Bowel Syndrome
|
nord_1112_1
|
Symptoms of Short Bowel Syndrome
|
The symptoms and severity of short bowel syndrome can vary greatly depending upon the length and function of the remaining or undamaged portion of the small intestine. Because short bowel syndrome can vary so greatly, it is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals or parents of affected children or infants should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.The small intestine is a long, narrow, accordion-like tube that extends from the stomach to the large intestine. It is the area where most of the digestion and absorption of nutrients occurs within the body. When the small intestine is damaged or lost (e.g., due to surgery), affected individuals may lose the ability to absorb sufficient amounts of water, vitamins and other nutrients from food.The small intestine is divided into three main sections: the duodenum, the jejunum and the ileum. In the adult, the normal length of the small intestine is estimated at 600cm (235 inches), and the colon is about 150cm (60 inches). Individuals who have only 150-200cm of the small intestine and lack a colon may have significant fluid and nutrient losses that often require the use of intravenous fluid and/or nutrients. These sections have different functions and are associated with the absorption of specific nutrients. For example, the duodenum is the first portion of the small intestine (about 30cm or 12 inches) and is connected to the stomach. The duodenum continues the breakdown of food particles from the stomach (the process of digestion) which prepares particles to be absorbed by the intestinal lining. The duodenum also absorbs iron, calcium and magnesium. The jejunum is the middle portion (mid-gut) of the small intestine and is where most nutrient absorption occurs. It is about 200cm (~80 inches) in length. Carbohydrates, fats, proteins, and vitamins are all absorbed in the jejunum. The ileum is the last portion of the small intestine and is connected to the large intestine. Some products of digestion that are not absorbed by the jejunum may also be absorbed by the ileum as this area can adapt to compensate for many of the jejunal functions. The reverse is not true. As there are special binding sites for the absorption of bile acids and vitamin B12 found only in the final portion of the ileum, referred to as the terminal ileum.Although symptoms of short bowel syndrome vary, diarrhea is common. Diarrhea can be severe and can cause dehydration, unintended weight loss, a general feeling of poor health (malaise), lethargy and eventually malnutrition. Additional symptoms include cramping, fatigue, weakness, bloating and heartburn. Individuals may have pale, greasy stools that contain excess amounts of fat (steatorrhea). Short bowel syndrome may cause malnutrition. Malnourishment can result in swelling (distention) of the abdomen, dehydration, loss of muscle mass, dry, flaky skin, swelling of the tissues of the legs and feet (peripheral edema), and weakening or wasting away of the muscle of the temples (temporal wasting) giving the temples a hollow appearance. Short bowel syndrome can lead to poor growth in infants and children due to undernutrition and lack of the proper building blocks for normal growth and development.A wide variety of additional symptoms may be associated with short bowel syndrome depending upon the failure to absorb sufficient levels of certain vitamins or minerals. Some examples of vitamin and mineral deficiencies and their potential symptoms are listed below.Deficiency of vitamin A can be associated with difficulties seeing at night (night blindness) and abnormal dryness and thickening of the conjunctiva and cornea (xerophthalmia). Affected individuals may develop corneal ulcerations. It also plays a role in healthy skin maintenance.Deficiency of vitamin B can lead to a variety of conditions include inflammation of the mouth (stomatitis) and tongue (glossitis), dry scaling of the lip (cheilosis), swelling due to fluid accumulation (edema), low levels of circulating red blood cells (anemia), weakness of certain eye muscles (ophthalmoplegia), irregular heartbeats (tachycardia or bradycardia), damage to the nerves outside the central nervous system (peripheral neuropathy) and seizures.Deficiency of vitamin D in children can result in rickets, a condition characterized by bow deformities of the legs, pain in the legs and progressive softening of the bone structure. In children, growth rates may also be slow, ultimately resulting in short stature. Affected individuals may be prone to fractures due to weakening of the bones (osteoporosis). Vitamin D deficiency can cause low calcium blood levels, which can also be associated with intermittent muscle spasms (tetany) and an abnormal sensation on the skin such as a feeling of being on “pins and needles” (paresthesias).Deficiency of vitamin E can result in paresthesias, tetany, loss of voluntary muscle coordination (ataxia), abnormal swelling due to fluid accumulation (edema), depressed deep tendon reflexes, and vision problems.Deficiency of vitamin K can cause prolonged bleeding and a tendency to bruise easily. Affected individuals may develop small red or purple pinprick-sized spots on the skin due to bleeding (petechiae), discoloration of the skin due to bleeding underneath the surface of the skin (ecchymoses) and a rash of purple spots on the skin due to internal bleeding (purpura).Iron deficiency may result in an unhealthy pale appearance or skin tone (pallor), inflammation of the tongue (glossitis), and abnormally spooned nails. In severe cases, it can cause weakness, fatigue, difficulty concentrating and short of breath upon exertion (dyspnea).Zinc deficiency can result in information of the mucous membrane of the mouth (stomatitis), patchy areas of hair loss (alopecia), poor wound healing and a reddened, scaly skin rash.Overgrowth of normal bacteria in the small intestine is common in children with short bowel syndrome, especially if they have an area of dilated small intestine with poor motility, which often happens in affected individuals. Exacerbation of bloating, diarrhea, and more severe nutrient malabsorption may occur in this setting.
|
Symptoms of Short Bowel Syndrome. The symptoms and severity of short bowel syndrome can vary greatly depending upon the length and function of the remaining or undamaged portion of the small intestine. Because short bowel syndrome can vary so greatly, it is important to note that affected individuals may not have all of the symptoms discussed below. Affected individuals or parents of affected children or infants should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.The small intestine is a long, narrow, accordion-like tube that extends from the stomach to the large intestine. It is the area where most of the digestion and absorption of nutrients occurs within the body. When the small intestine is damaged or lost (e.g., due to surgery), affected individuals may lose the ability to absorb sufficient amounts of water, vitamins and other nutrients from food.The small intestine is divided into three main sections: the duodenum, the jejunum and the ileum. In the adult, the normal length of the small intestine is estimated at 600cm (235 inches), and the colon is about 150cm (60 inches). Individuals who have only 150-200cm of the small intestine and lack a colon may have significant fluid and nutrient losses that often require the use of intravenous fluid and/or nutrients. These sections have different functions and are associated with the absorption of specific nutrients. For example, the duodenum is the first portion of the small intestine (about 30cm or 12 inches) and is connected to the stomach. The duodenum continues the breakdown of food particles from the stomach (the process of digestion) which prepares particles to be absorbed by the intestinal lining. The duodenum also absorbs iron, calcium and magnesium. The jejunum is the middle portion (mid-gut) of the small intestine and is where most nutrient absorption occurs. It is about 200cm (~80 inches) in length. Carbohydrates, fats, proteins, and vitamins are all absorbed in the jejunum. The ileum is the last portion of the small intestine and is connected to the large intestine. Some products of digestion that are not absorbed by the jejunum may also be absorbed by the ileum as this area can adapt to compensate for many of the jejunal functions. The reverse is not true. As there are special binding sites for the absorption of bile acids and vitamin B12 found only in the final portion of the ileum, referred to as the terminal ileum.Although symptoms of short bowel syndrome vary, diarrhea is common. Diarrhea can be severe and can cause dehydration, unintended weight loss, a general feeling of poor health (malaise), lethargy and eventually malnutrition. Additional symptoms include cramping, fatigue, weakness, bloating and heartburn. Individuals may have pale, greasy stools that contain excess amounts of fat (steatorrhea). Short bowel syndrome may cause malnutrition. Malnourishment can result in swelling (distention) of the abdomen, dehydration, loss of muscle mass, dry, flaky skin, swelling of the tissues of the legs and feet (peripheral edema), and weakening or wasting away of the muscle of the temples (temporal wasting) giving the temples a hollow appearance. Short bowel syndrome can lead to poor growth in infants and children due to undernutrition and lack of the proper building blocks for normal growth and development.A wide variety of additional symptoms may be associated with short bowel syndrome depending upon the failure to absorb sufficient levels of certain vitamins or minerals. Some examples of vitamin and mineral deficiencies and their potential symptoms are listed below.Deficiency of vitamin A can be associated with difficulties seeing at night (night blindness) and abnormal dryness and thickening of the conjunctiva and cornea (xerophthalmia). Affected individuals may develop corneal ulcerations. It also plays a role in healthy skin maintenance.Deficiency of vitamin B can lead to a variety of conditions include inflammation of the mouth (stomatitis) and tongue (glossitis), dry scaling of the lip (cheilosis), swelling due to fluid accumulation (edema), low levels of circulating red blood cells (anemia), weakness of certain eye muscles (ophthalmoplegia), irregular heartbeats (tachycardia or bradycardia), damage to the nerves outside the central nervous system (peripheral neuropathy) and seizures.Deficiency of vitamin D in children can result in rickets, a condition characterized by bow deformities of the legs, pain in the legs and progressive softening of the bone structure. In children, growth rates may also be slow, ultimately resulting in short stature. Affected individuals may be prone to fractures due to weakening of the bones (osteoporosis). Vitamin D deficiency can cause low calcium blood levels, which can also be associated with intermittent muscle spasms (tetany) and an abnormal sensation on the skin such as a feeling of being on “pins and needles” (paresthesias).Deficiency of vitamin E can result in paresthesias, tetany, loss of voluntary muscle coordination (ataxia), abnormal swelling due to fluid accumulation (edema), depressed deep tendon reflexes, and vision problems.Deficiency of vitamin K can cause prolonged bleeding and a tendency to bruise easily. Affected individuals may develop small red or purple pinprick-sized spots on the skin due to bleeding (petechiae), discoloration of the skin due to bleeding underneath the surface of the skin (ecchymoses) and a rash of purple spots on the skin due to internal bleeding (purpura).Iron deficiency may result in an unhealthy pale appearance or skin tone (pallor), inflammation of the tongue (glossitis), and abnormally spooned nails. In severe cases, it can cause weakness, fatigue, difficulty concentrating and short of breath upon exertion (dyspnea).Zinc deficiency can result in information of the mucous membrane of the mouth (stomatitis), patchy areas of hair loss (alopecia), poor wound healing and a reddened, scaly skin rash.Overgrowth of normal bacteria in the small intestine is common in children with short bowel syndrome, especially if they have an area of dilated small intestine with poor motility, which often happens in affected individuals. Exacerbation of bloating, diarrhea, and more severe nutrient malabsorption may occur in this setting.
| 1,112 |
Short Bowel Syndrome
|
nord_1112_2
|
Causes of Short Bowel Syndrome
|
Short bowel syndrome is generally broken down into individuals in whom the disorder is acquired during life and newborns in which the disorder is present at birth (congenital). Acquired short bowel syndrome is more common than the congenital form of the disorder.Surgical removal (resection) of a portion of the small intestine is the most common cause of short bowel syndrome. However, short bowel syndrome can result from any disease, injury or condition that hinders or prevents the proper function of the small intestine, even if the overall length of the bowel is unaffected.In infants and newborns, the most common reason for surgical resection of the small intestine is necrotizing enterocolitis, a condition characterized by tissue loss of the intestines. Specifically, the lining of the intestinal wall dies and falls off. The lining of the intestine is where absorption occurs. The cause for this tissue loss is not always understood, but usually necessitates the surgical removal of the affected portion of the small intestine. Necrotizing enterocolitis most often occurs in infants that are premature or have an underlying illness.Additional conditions that can lead to surgical resection of a portion of the small intestine in newborns include congenital defects of the bowel such as midgut volvulus, a condition in which a portion of the bowel is twisted back around itself; omphalocele, a birth defect in which a portion of the intestine and other abdominal structures stick out from the bellybutton; gastroschisis, a birth defect in which a portion of the intestine sticks out through a hole on one side of umbilical cord; and meconium ileus, a condition associated with cystic fibrosis that is characterized by obstruction of the intestine by meconium, the dark sticky substance that is normally present in the intestine at birth. Abnormal intestinal development before birth can result in narrowing (atresia) of portions of the small intestine and can result in short bowel syndrome. Certain congenital diseases of the gastrointestinal tract such as microvillus inclusion disease may cause such severe impairment of absorption as to mimic short bowel syndrome. Hirschsprung’s disease may in rare instances extend into the small intestine and can also result in short bowel syndrome.In some cases, newborns can be born with a shortened bowel that is present at birth (congenital short bowel syndrome). The exact cause of a short bowel in these cases is not fully understood and several different theories have been proposed. More research is necessary to determine what factors ultimately lead to congenital short bowel syndrome.In older children and adults, causes of short bowel syndrome include Crohn’s disease; folding of a portion of the intestines into another portion (intussusception); damage to the small intestines because of trauma; damage to the small intestines from lack of blood flow (ischemia) due to a blocked blood vessel, diseases of the blood vessels, or overactive blood clotting disorders (hypercoagulable states); damage to the small intestine from cancer or from the treatment of cancer including surgical removal of a cancerous section of the small intestine or radiation enteritis. Radiation enteritis is damage to the lining of the intestine because of radiation therapy and can affect both the small and large intestines.The removal or loss of a segment of the small intestine does not necessarily result in short bowel syndrome. Often, additional factors play a role in the eventual development of the disorder. Such factors include the following: the specific segment of the intestines that is lost, the remaining length of the small intestines, whether the colon is intact, whether the valve at the junction of the small and large intestines (ileocecal valve) is intact, the presence and nature of any underlying disease, and the age and overall health of the individual. Also, with appropriate rehabilitation, the remaining healthy small intestine will undergo a process of adaptation with time, and the intestinal lining may grow larger (hypertrophy) and ultimately absorb more, which may lessen an individual’s particular symptoms.
|
Causes of Short Bowel Syndrome. Short bowel syndrome is generally broken down into individuals in whom the disorder is acquired during life and newborns in which the disorder is present at birth (congenital). Acquired short bowel syndrome is more common than the congenital form of the disorder.Surgical removal (resection) of a portion of the small intestine is the most common cause of short bowel syndrome. However, short bowel syndrome can result from any disease, injury or condition that hinders or prevents the proper function of the small intestine, even if the overall length of the bowel is unaffected.In infants and newborns, the most common reason for surgical resection of the small intestine is necrotizing enterocolitis, a condition characterized by tissue loss of the intestines. Specifically, the lining of the intestinal wall dies and falls off. The lining of the intestine is where absorption occurs. The cause for this tissue loss is not always understood, but usually necessitates the surgical removal of the affected portion of the small intestine. Necrotizing enterocolitis most often occurs in infants that are premature or have an underlying illness.Additional conditions that can lead to surgical resection of a portion of the small intestine in newborns include congenital defects of the bowel such as midgut volvulus, a condition in which a portion of the bowel is twisted back around itself; omphalocele, a birth defect in which a portion of the intestine and other abdominal structures stick out from the bellybutton; gastroschisis, a birth defect in which a portion of the intestine sticks out through a hole on one side of umbilical cord; and meconium ileus, a condition associated with cystic fibrosis that is characterized by obstruction of the intestine by meconium, the dark sticky substance that is normally present in the intestine at birth. Abnormal intestinal development before birth can result in narrowing (atresia) of portions of the small intestine and can result in short bowel syndrome. Certain congenital diseases of the gastrointestinal tract such as microvillus inclusion disease may cause such severe impairment of absorption as to mimic short bowel syndrome. Hirschsprung’s disease may in rare instances extend into the small intestine and can also result in short bowel syndrome.In some cases, newborns can be born with a shortened bowel that is present at birth (congenital short bowel syndrome). The exact cause of a short bowel in these cases is not fully understood and several different theories have been proposed. More research is necessary to determine what factors ultimately lead to congenital short bowel syndrome.In older children and adults, causes of short bowel syndrome include Crohn’s disease; folding of a portion of the intestines into another portion (intussusception); damage to the small intestines because of trauma; damage to the small intestines from lack of blood flow (ischemia) due to a blocked blood vessel, diseases of the blood vessels, or overactive blood clotting disorders (hypercoagulable states); damage to the small intestine from cancer or from the treatment of cancer including surgical removal of a cancerous section of the small intestine or radiation enteritis. Radiation enteritis is damage to the lining of the intestine because of radiation therapy and can affect both the small and large intestines.The removal or loss of a segment of the small intestine does not necessarily result in short bowel syndrome. Often, additional factors play a role in the eventual development of the disorder. Such factors include the following: the specific segment of the intestines that is lost, the remaining length of the small intestines, whether the colon is intact, whether the valve at the junction of the small and large intestines (ileocecal valve) is intact, the presence and nature of any underlying disease, and the age and overall health of the individual. Also, with appropriate rehabilitation, the remaining healthy small intestine will undergo a process of adaptation with time, and the intestinal lining may grow larger (hypertrophy) and ultimately absorb more, which may lessen an individual’s particular symptoms.
| 1,112 |
Short Bowel Syndrome
|
nord_1112_3
|
Affects of Short Bowel Syndrome
|
Short bowel syndrome affects males and females in equal numbers. The disorder is usually acquired during life, but in rare cases may be present at birth (congenital). In adults, short bowel syndrome usually results from the surgical removal of a portion of the small intestine. Crohn’s disease is the most frequent cause of surgical removal of the small intestine in adults. In newborns, necrotizing enterocolitis is the most common cause of surgical removal of the small intestines. The exact incidence and prevalence of short bowel syndrome in the general population is unknown.
|
Affects of Short Bowel Syndrome. Short bowel syndrome affects males and females in equal numbers. The disorder is usually acquired during life, but in rare cases may be present at birth (congenital). In adults, short bowel syndrome usually results from the surgical removal of a portion of the small intestine. Crohn’s disease is the most frequent cause of surgical removal of the small intestine in adults. In newborns, necrotizing enterocolitis is the most common cause of surgical removal of the small intestines. The exact incidence and prevalence of short bowel syndrome in the general population is unknown.
| 1,112 |
Short Bowel Syndrome
|
nord_1112_4
|
Related disorders of Short Bowel Syndrome
|
Related disorders of Short Bowel Syndrome.
| 1,112 |
Short Bowel Syndrome
|
|
nord_1112_5
|
Diagnosis of Short Bowel Syndrome
|
A diagnosis of short bowel syndrome is made based upon a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including laboratory tests and X-ray studies.Clinical Testing and Work-Up
An important laboratory test is a complete blood count (CBC), which is used to check for anemia. Additional laboratory tests may be performed to assess the levels of albumin, which may indicate poor nutritional status when low and dehydration when high; liver enzymes, which may indicate liver cell damage when persistently elevated; electrolyte abnormalities, which may indicate deficiencies or dehydration; and creatinine, which indicates function of the kidneys. Laboratory tests may also be used to detect deficiencies of vitamins or minerals, which can occur with short bowel syndrome.Imaging techniques may be used to assess individuals with short bowel syndrome. Such tests include plain abdominal X-rays to detect signs of obstruction or ileus (paralysis of intestinal muscles), computerized tomography (CT) scanning of the abdomen (abdominal CAT scan), magnetic resonance imaging (MRI) of the abdomen or an abdominal ultrasound. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of certain tissue structures. An abdominal CAT scan enables physicians to identify problems such as bowel obstruction and assess the health of the liver. An abdominal ultrasound may be used to detect biliary sludge or gallstones, which are often associated with short bowel syndrome. An upper gastrointestinal series (an x-ray that examines the upper and middle portion of the gastrointestinal system) with a small bowel follow through and abdominal MRI (imaging which does not involve radiation exposure), allows physicians to detect areas of stricture (narrowing) or abnormal connections (fistulas) within the small bowels and assess the health of the lining of the small bowel.Additional tests may be performed to detect or assess potential complications of short bowel syndrome. For example, a liver biopsy may be performed to assess the health and function of the liver. Upper and lower endoscopic studies may also help in the evaluation of the function of the remaining intestine.
|
Diagnosis of Short Bowel Syndrome. A diagnosis of short bowel syndrome is made based upon a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including laboratory tests and X-ray studies.Clinical Testing and Work-Up
An important laboratory test is a complete blood count (CBC), which is used to check for anemia. Additional laboratory tests may be performed to assess the levels of albumin, which may indicate poor nutritional status when low and dehydration when high; liver enzymes, which may indicate liver cell damage when persistently elevated; electrolyte abnormalities, which may indicate deficiencies or dehydration; and creatinine, which indicates function of the kidneys. Laboratory tests may also be used to detect deficiencies of vitamins or minerals, which can occur with short bowel syndrome.Imaging techniques may be used to assess individuals with short bowel syndrome. Such tests include plain abdominal X-rays to detect signs of obstruction or ileus (paralysis of intestinal muscles), computerized tomography (CT) scanning of the abdomen (abdominal CAT scan), magnetic resonance imaging (MRI) of the abdomen or an abdominal ultrasound. During CT scanning, a computer and X-rays are used to create a film showing cross-sectional images of certain tissue structures. An abdominal CAT scan enables physicians to identify problems such as bowel obstruction and assess the health of the liver. An abdominal ultrasound may be used to detect biliary sludge or gallstones, which are often associated with short bowel syndrome. An upper gastrointestinal series (an x-ray that examines the upper and middle portion of the gastrointestinal system) with a small bowel follow through and abdominal MRI (imaging which does not involve radiation exposure), allows physicians to detect areas of stricture (narrowing) or abnormal connections (fistulas) within the small bowels and assess the health of the lining of the small bowel.Additional tests may be performed to detect or assess potential complications of short bowel syndrome. For example, a liver biopsy may be performed to assess the health and function of the liver. Upper and lower endoscopic studies may also help in the evaluation of the function of the remaining intestine.
| 1,112 |
Short Bowel Syndrome
|
nord_1112_6
|
Therapies of Short Bowel Syndrome
|
TreatmentThe treatment of short bowel syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatric gastroenterologists, surgeons, adult gastroenterologists, dietitians, nutritionists and other healthcare professionals (social work and psychology) may need to systematically and comprehensively plan an affected individual’s treatment.The specific therapeutic procedures and interventions for individuals with a short bowel syndrome will vary, depending upon numerous factors including the specific symptoms present, the site and extent of the affected portion of the small intestine, whether the colon is involved, an individual’s age and overall health, tolerance of certain medications or procedures, personal preference and other factors. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Treatment options that may be used to treat individuals with short bowel syndrome are complex and varied. The specific treatment plan may be highly individualized and can include total parenteral nutrition (TPN [intravenous fluid and nutrition therapy]), enteral feeding, dietary adjustments, oral rehydration solutions, certain medications and/or surgery. Maintaining proper nutritional intake is vital for individuals with short bowel syndrome.In mild cases, slowly increasing the oral intake of food and taking certain supplements or medications for diarrhea may be all that is required. However, in many cases TPN is necessary and, in severe cases, short bowel syndrome may potentially require a small bowel transplant. In recent years, advances in therapy including new options like recombinant growth hormone and glucagon-like peptide analogs and improvements in surgical techniques have lessened the length of time that individuals must remain on TPN.INTESTINAL ADAPTION
Treatment for individuals with short bowel syndrome is specially designed to quicken or strengthen the process of intestinal adaption and to supply sufficient nutritional support. Intestinal adaption is the process by which the remaining or functional portion of the small bowel can adapt and increase its absorption to compensate for the missing or nonfunctioning segments. The amount of time intestinal adaption can take to occur is controversial. Originally, it was believed to occur only within 6 months of the loss of a portion of the small bowel. Now, many physicians believe it can occur as late as 2-3 years later. Researchers are investigating more ways to further stimulate intestinal adaption and to help the remaining small intestines to increase absorption and to function better.NUTRITIONAL MANAGEMENT
After surgical removal of a portion of the small intestine, many individuals are put on TPN, which supplies all daily nutritional requirements such as protein, sugars, vitamins, minerals, trace elements and sometimes fats. TPN is a way to bypass how the body normally digests food. With TPN, a special intravenous (IV) line is inserted into a large vein and nutrients are delivered directly into the bloodstream. The first few doses of TPN are given in the hospital. Eventually, TPN can be given at home. The amount of time a person requires TPN varies. For some individuals, TPN may be a lifelong requirement.Long-term use of TPN can be associated with a variety of complications including bacterial infections, intravenous catheter complications, low bone calcium uptake, blood clots, gallbladder disease, kidney disease and liver problems. Liver and kidney problems can ultimately result in liver or kidney failure.Eventually, some individuals with short bowel syndrome will be able to discontinue TPN. Individuals may be weaned off TPN through diet, medications and, sometimes, surgery. When intestinal function improves, affected individuals may be treated via enteral feeding. Enteral feeding is the use of a tube to deliver food directly into the stomach or small bowel. Eventually, affected individuals are given small amounts of food orally. It is important that infants receive small amounts of food orally in order for them to learn how to suck and swallow.DIET
Affected individuals will be encouraged to eat whenever possible because eating stimulates intestinal absorption and promotes intestinal adaption. This is especially important because TPN bypasses the stomach and intestines altogether. There is no specific diet for individuals with short bowel syndrome. A diet will be individualized based on specific factors including what portion of the small bowel is affected and how well the remaining bowel is functioning. For example, individuals with an intact colon are recommended to follow a high-carbohydrate, low-fat diet. Infants and children, especially those at high risk for the development of small bowel bacterial overgrowth, may benefit from a higher fat diet to reduce bacterial proliferation and enhanced intestinal adaptation.Individuals with short bowel syndrome are often encouraged to eat five or more small meals a day as opposed to two or three large meals. Concentrated sugars should be avoided or minimized because they can contribute to diarrhea. Some individuals may need to take additional vitamin or mineral supplementation to make up for deficiencies of these substances.In addition to adjustments in diet, affected individuals may be given oral rehydration solutions. These solutions are used to maintain proper fluid balance. Generally, these solutions consist of water, sugar and salt. In some cases, they can reduce the need for parenteral nutrition.MEDICATIONS
A variety of medications may be used to treat individuals with short bowel syndrome.Gattex (teduglutide) was approved by the U.S. Food and Drug Administration (FDA) in 2012 to treat adults with short bowel syndrome. This drug is a form of glucagon-like peptide 2 which is a protein involved in the adaptation/rehabilitation of the lining (mucosa) of the intestines.Drugs that help treat diarrhea (anti-diarrheals) are often used. Such drugs include diphenoxylate and loperamide. Codeine may also be prescribed as an anti-diarrheal. In individuals who do not respond to those drugs, opium tincture may be tried. Many of these drugs increase the time it takes for food to pass through the intestines by slowing peristalsis. Peristalsis refers to the contraction and relaxation of the muscles lining the intestines that push food through the digestive tract. Slowing peristalsis allows food to spend more time in the intestines, thereby enabling a greater amount of absorption and reducing diarrhea.In patients with severe short bowel syndrome, the absorption of medications may be an important issue. Higher doses of medications may be required to offset the lower percentage of absorption. Extended release medications are generally to be avoided. Sometimes different delivery systems such as skin patches, nasal or other routes need to be considered to deliver a particular medication to an individual.In some severe cases (e.g. cases in which individuals have lost all of their colon and ileum and some of the jejunum) or in individuals who do not respond to other medications, the somatostatin analogue, octreotide, may be tried. Octreotide can significantly reduce diarrhea in some cases. However, octreotide can also inhibit intestinal adaption by preventing the release of important hormonal secretions.Drugs that prevent or reduce the release of stomach acid (e.g., histamine-2 receptor blockers and proton pump inhibitors) may also be used to treat individuals with short bowel syndrome. Examples of such drugs include famotidine, ranitidine, omeprazole and lansoprazole. Evidence suggests that excess acid secretions (hypersecretion) from the stomach can hinder intestinal adaption. These drugs are usually given early during the postoperative period when hypersecretion is greatest.Somatropin (rDNA origin) for injection (Zorbtive), a human growth hormone, has been approved by the Food and Drug Administration (FDA) for the treatment of individuals with short bowel syndrome. Zorbtive is similar to the growth hormone produced by the pituitary gland. This drug can improve the ability of the small intestine to absorb nutrients, thereby lessening the need for TPN. Zorbtive is approved specifically for individuals with short bowel syndrome who rely on a special diet, which often includes TPN.Pancreatic enzyme replacement therapy such as pancrelipase and bile-acid resins such as cholestyramine may be given to some individuals with short bowel syndrome. Because food spends less time in the digestive system it has less opportunity to mix with normal pancreatic and biliary secretions that aid digestion.In rare cases, where affected individuals develop bacterial overgrowth, antibiotics that destroy or inhibit the growth of harmful microorganisms may be recommended. Probiotics may be used to provide beneficial bacteria to the intestinal population.In infants and small children with short bowel syndrome, liver injury secondary to intravenous nutrition is common. Reduction in the amount of soy-based intravenous lipid solutions or use of fish oil based lipid emulsions appears to significantly improve the prognosis.SURGERY
A variety of surgical techniques has been used to treat individuals with short bowel syndrome. Generally, surgery is used as a last resort in individuals in whom other therapeutic options have not worked. However, as surgical techniques improve, they may eventually be considered a front-line option. Surgical options for short bowel syndrome are sometimes broken down into non-transplant and transplant surgeries.Non-transplant Surgery
Artificially lengthening the intestines has been used to treat individuals with short bowel syndrome. Two main procedures have been used the Bianchi procedure and the STEP procedure. During the Bianchi procedure, a portion of the dilated bowel is divided lengthwise into two segments. These segments are separated and joined end to end, resulting in a narrower, but longer segment of bowel.STEP is an acronym for serial transverse enteroplasty. This procedure is usually performed in children who have enough small bowel remaining that surgeons can lengthen the bowel and restore function. During this procedure, a surgeon creates small cuts or notches into both sides of a widened portion of the short bowel. This creates a “zig-zag” shaped bowel that is narrower, but longer. The STEP procedure will result in food taking longer to move through the bowel, spending more time in contact with the lining of the bowel and enabling a greater chance of absorption.Stricturoplasty is a procedure to widen a narrowed area of the bowel. This procedure is often done for individuals with Crohn’s disease to prevent the need for large or multiple resections of the bowel.Some segments of the small bowel may become abnormally widened (dilated) potentially allowing fluid to pool and bacteria to develop. Some procedures are done to narrow abnormally widened segments of the bowels. This is known as intestinal tapering.Procedures that can reconnect the small bowel to the colon to establish continuity have also demonstrated benefit in treating individuals with short bowel syndrome.Transplant Surgery
A small bowel transplant may be an option for some individuals with short bowel syndrome, especially those who have complications from TPN such as liver failure or who were unable to maintain proper nutrition with other therapies. During a small bowel transplant, the disease small bowel is removed and replaced with one from a healthy donor. A variety of complications can occur with small bowel transplantation including organ rejection, infections, and lymphoproliferative disease. In addition, the procedure is expensive and requires the lifelong use of immunosuppressive drugs to lessen the chance of rejection. However, as surgical techniques and immunosuppressive agents improve in efficacy, survival has improved as well. Some individuals may receive a small bowel transplant along with a liver transplant (i.e., in cases with impending or frank liver failure) or other organs such as kidney or pancreas.
|
Therapies of Short Bowel Syndrome. TreatmentThe treatment of short bowel syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatric gastroenterologists, surgeons, adult gastroenterologists, dietitians, nutritionists and other healthcare professionals (social work and psychology) may need to systematically and comprehensively plan an affected individual’s treatment.The specific therapeutic procedures and interventions for individuals with a short bowel syndrome will vary, depending upon numerous factors including the specific symptoms present, the site and extent of the affected portion of the small intestine, whether the colon is involved, an individual’s age and overall health, tolerance of certain medications or procedures, personal preference and other factors. Decisions concerning the use of particular therapeutic interventions should be made by physicians and other members of the healthcare team in careful consultation with the patient and/or parents based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.Treatment options that may be used to treat individuals with short bowel syndrome are complex and varied. The specific treatment plan may be highly individualized and can include total parenteral nutrition (TPN [intravenous fluid and nutrition therapy]), enteral feeding, dietary adjustments, oral rehydration solutions, certain medications and/or surgery. Maintaining proper nutritional intake is vital for individuals with short bowel syndrome.In mild cases, slowly increasing the oral intake of food and taking certain supplements or medications for diarrhea may be all that is required. However, in many cases TPN is necessary and, in severe cases, short bowel syndrome may potentially require a small bowel transplant. In recent years, advances in therapy including new options like recombinant growth hormone and glucagon-like peptide analogs and improvements in surgical techniques have lessened the length of time that individuals must remain on TPN.INTESTINAL ADAPTION
Treatment for individuals with short bowel syndrome is specially designed to quicken or strengthen the process of intestinal adaption and to supply sufficient nutritional support. Intestinal adaption is the process by which the remaining or functional portion of the small bowel can adapt and increase its absorption to compensate for the missing or nonfunctioning segments. The amount of time intestinal adaption can take to occur is controversial. Originally, it was believed to occur only within 6 months of the loss of a portion of the small bowel. Now, many physicians believe it can occur as late as 2-3 years later. Researchers are investigating more ways to further stimulate intestinal adaption and to help the remaining small intestines to increase absorption and to function better.NUTRITIONAL MANAGEMENT
After surgical removal of a portion of the small intestine, many individuals are put on TPN, which supplies all daily nutritional requirements such as protein, sugars, vitamins, minerals, trace elements and sometimes fats. TPN is a way to bypass how the body normally digests food. With TPN, a special intravenous (IV) line is inserted into a large vein and nutrients are delivered directly into the bloodstream. The first few doses of TPN are given in the hospital. Eventually, TPN can be given at home. The amount of time a person requires TPN varies. For some individuals, TPN may be a lifelong requirement.Long-term use of TPN can be associated with a variety of complications including bacterial infections, intravenous catheter complications, low bone calcium uptake, blood clots, gallbladder disease, kidney disease and liver problems. Liver and kidney problems can ultimately result in liver or kidney failure.Eventually, some individuals with short bowel syndrome will be able to discontinue TPN. Individuals may be weaned off TPN through diet, medications and, sometimes, surgery. When intestinal function improves, affected individuals may be treated via enteral feeding. Enteral feeding is the use of a tube to deliver food directly into the stomach or small bowel. Eventually, affected individuals are given small amounts of food orally. It is important that infants receive small amounts of food orally in order for them to learn how to suck and swallow.DIET
Affected individuals will be encouraged to eat whenever possible because eating stimulates intestinal absorption and promotes intestinal adaption. This is especially important because TPN bypasses the stomach and intestines altogether. There is no specific diet for individuals with short bowel syndrome. A diet will be individualized based on specific factors including what portion of the small bowel is affected and how well the remaining bowel is functioning. For example, individuals with an intact colon are recommended to follow a high-carbohydrate, low-fat diet. Infants and children, especially those at high risk for the development of small bowel bacterial overgrowth, may benefit from a higher fat diet to reduce bacterial proliferation and enhanced intestinal adaptation.Individuals with short bowel syndrome are often encouraged to eat five or more small meals a day as opposed to two or three large meals. Concentrated sugars should be avoided or minimized because they can contribute to diarrhea. Some individuals may need to take additional vitamin or mineral supplementation to make up for deficiencies of these substances.In addition to adjustments in diet, affected individuals may be given oral rehydration solutions. These solutions are used to maintain proper fluid balance. Generally, these solutions consist of water, sugar and salt. In some cases, they can reduce the need for parenteral nutrition.MEDICATIONS
A variety of medications may be used to treat individuals with short bowel syndrome.Gattex (teduglutide) was approved by the U.S. Food and Drug Administration (FDA) in 2012 to treat adults with short bowel syndrome. This drug is a form of glucagon-like peptide 2 which is a protein involved in the adaptation/rehabilitation of the lining (mucosa) of the intestines.Drugs that help treat diarrhea (anti-diarrheals) are often used. Such drugs include diphenoxylate and loperamide. Codeine may also be prescribed as an anti-diarrheal. In individuals who do not respond to those drugs, opium tincture may be tried. Many of these drugs increase the time it takes for food to pass through the intestines by slowing peristalsis. Peristalsis refers to the contraction and relaxation of the muscles lining the intestines that push food through the digestive tract. Slowing peristalsis allows food to spend more time in the intestines, thereby enabling a greater amount of absorption and reducing diarrhea.In patients with severe short bowel syndrome, the absorption of medications may be an important issue. Higher doses of medications may be required to offset the lower percentage of absorption. Extended release medications are generally to be avoided. Sometimes different delivery systems such as skin patches, nasal or other routes need to be considered to deliver a particular medication to an individual.In some severe cases (e.g. cases in which individuals have lost all of their colon and ileum and some of the jejunum) or in individuals who do not respond to other medications, the somatostatin analogue, octreotide, may be tried. Octreotide can significantly reduce diarrhea in some cases. However, octreotide can also inhibit intestinal adaption by preventing the release of important hormonal secretions.Drugs that prevent or reduce the release of stomach acid (e.g., histamine-2 receptor blockers and proton pump inhibitors) may also be used to treat individuals with short bowel syndrome. Examples of such drugs include famotidine, ranitidine, omeprazole and lansoprazole. Evidence suggests that excess acid secretions (hypersecretion) from the stomach can hinder intestinal adaption. These drugs are usually given early during the postoperative period when hypersecretion is greatest.Somatropin (rDNA origin) for injection (Zorbtive), a human growth hormone, has been approved by the Food and Drug Administration (FDA) for the treatment of individuals with short bowel syndrome. Zorbtive is similar to the growth hormone produced by the pituitary gland. This drug can improve the ability of the small intestine to absorb nutrients, thereby lessening the need for TPN. Zorbtive is approved specifically for individuals with short bowel syndrome who rely on a special diet, which often includes TPN.Pancreatic enzyme replacement therapy such as pancrelipase and bile-acid resins such as cholestyramine may be given to some individuals with short bowel syndrome. Because food spends less time in the digestive system it has less opportunity to mix with normal pancreatic and biliary secretions that aid digestion.In rare cases, where affected individuals develop bacterial overgrowth, antibiotics that destroy or inhibit the growth of harmful microorganisms may be recommended. Probiotics may be used to provide beneficial bacteria to the intestinal population.In infants and small children with short bowel syndrome, liver injury secondary to intravenous nutrition is common. Reduction in the amount of soy-based intravenous lipid solutions or use of fish oil based lipid emulsions appears to significantly improve the prognosis.SURGERY
A variety of surgical techniques has been used to treat individuals with short bowel syndrome. Generally, surgery is used as a last resort in individuals in whom other therapeutic options have not worked. However, as surgical techniques improve, they may eventually be considered a front-line option. Surgical options for short bowel syndrome are sometimes broken down into non-transplant and transplant surgeries.Non-transplant Surgery
Artificially lengthening the intestines has been used to treat individuals with short bowel syndrome. Two main procedures have been used the Bianchi procedure and the STEP procedure. During the Bianchi procedure, a portion of the dilated bowel is divided lengthwise into two segments. These segments are separated and joined end to end, resulting in a narrower, but longer segment of bowel.STEP is an acronym for serial transverse enteroplasty. This procedure is usually performed in children who have enough small bowel remaining that surgeons can lengthen the bowel and restore function. During this procedure, a surgeon creates small cuts or notches into both sides of a widened portion of the short bowel. This creates a “zig-zag” shaped bowel that is narrower, but longer. The STEP procedure will result in food taking longer to move through the bowel, spending more time in contact with the lining of the bowel and enabling a greater chance of absorption.Stricturoplasty is a procedure to widen a narrowed area of the bowel. This procedure is often done for individuals with Crohn’s disease to prevent the need for large or multiple resections of the bowel.Some segments of the small bowel may become abnormally widened (dilated) potentially allowing fluid to pool and bacteria to develop. Some procedures are done to narrow abnormally widened segments of the bowels. This is known as intestinal tapering.Procedures that can reconnect the small bowel to the colon to establish continuity have also demonstrated benefit in treating individuals with short bowel syndrome.Transplant Surgery
A small bowel transplant may be an option for some individuals with short bowel syndrome, especially those who have complications from TPN such as liver failure or who were unable to maintain proper nutrition with other therapies. During a small bowel transplant, the disease small bowel is removed and replaced with one from a healthy donor. A variety of complications can occur with small bowel transplantation including organ rejection, infections, and lymphoproliferative disease. In addition, the procedure is expensive and requires the lifelong use of immunosuppressive drugs to lessen the chance of rejection. However, as surgical techniques and immunosuppressive agents improve in efficacy, survival has improved as well. Some individuals may receive a small bowel transplant along with a liver transplant (i.e., in cases with impending or frank liver failure) or other organs such as kidney or pancreas.
| 1,112 |
Short Bowel Syndrome
|
nord_1113_0
|
Overview of Short Chain Acyl CoA Dehydrogenase Deficiency
|
Short chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive genetic defect in fatty acid catabolism belonging to a group of diseases known as fatty acid oxidation disorders (FOD). It occurs because of a deficiency of the short-chain acyl-CoA dehydrogenase (SCAD) enzyme.Although SCADD was initially thought to produce severe problems including progressive muscle weakness, hypotonia, acidemia, developmental delay, and even early death, it is now believed that this deficiency has no clinical relevance. Since the advent of expanded newborn screening programs using tandem mass spectrometry technology, many more SCADD infants are being detected, all of whom are asymptomatic.When symptoms are present, additional diagnostic testing for another condition should be performed as the association is likely coincidental rather than causative.
|
Overview of Short Chain Acyl CoA Dehydrogenase Deficiency. Short chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive genetic defect in fatty acid catabolism belonging to a group of diseases known as fatty acid oxidation disorders (FOD). It occurs because of a deficiency of the short-chain acyl-CoA dehydrogenase (SCAD) enzyme.Although SCADD was initially thought to produce severe problems including progressive muscle weakness, hypotonia, acidemia, developmental delay, and even early death, it is now believed that this deficiency has no clinical relevance. Since the advent of expanded newborn screening programs using tandem mass spectrometry technology, many more SCADD infants are being detected, all of whom are asymptomatic.When symptoms are present, additional diagnostic testing for another condition should be performed as the association is likely coincidental rather than causative.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_1
|
Symptoms of Short Chain Acyl CoA Dehydrogenase Deficiency
|
Essentially all individuals identified through newborn screening have been healthy. Therefore, the variety of symptoms that have been reported in other individuals with SCAD deficiency are all likely coincidental. This situation has been accentuated by the existence of two very common variants in the SCAD gene that lead to blood and urine findings suggestive of SCADD but are not sufficiently severe to cause complete SCADD.
|
Symptoms of Short Chain Acyl CoA Dehydrogenase Deficiency. Essentially all individuals identified through newborn screening have been healthy. Therefore, the variety of symptoms that have been reported in other individuals with SCAD deficiency are all likely coincidental. This situation has been accentuated by the existence of two very common variants in the SCAD gene that lead to blood and urine findings suggestive of SCADD but are not sufficiently severe to cause complete SCADD.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_2
|
Causes of Short Chain Acyl CoA Dehydrogenase Deficiency
|
SCADD is an autosomal recessive condition caused by mutations in the Short Chain Acyl-Coenzyme A dehydrogenase (ACADS) gene leading to deficiency of the SCAD enzyme.The SCAD enzyme is involved in the breakdown of complex fatty acids into more simple substances. This takes place in the cell’s mitochondria, small, well-defined bodies found in all cells in which energy is generated from the breakdown of complex substances into simpler ones (mitochondrial oxidation). Because this enzyme occurs at the very end of the fatty acid oxidation pathway, the compounds that accumulate can be utilized by other enzymes, preventing clinical symptoms from occurring.More than 100 different mutations in the ACADS gene cause SCADD. Two common variations (polymorphisms) have also been found in the ACADS gene. It has been suggested that SCAD deficiency may be a risk factor that can make other neuromuscular disorders worse, but this remains unproven. 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 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. All individuals carry a few 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.
|
Causes of Short Chain Acyl CoA Dehydrogenase Deficiency. SCADD is an autosomal recessive condition caused by mutations in the Short Chain Acyl-Coenzyme A dehydrogenase (ACADS) gene leading to deficiency of the SCAD enzyme.The SCAD enzyme is involved in the breakdown of complex fatty acids into more simple substances. This takes place in the cell’s mitochondria, small, well-defined bodies found in all cells in which energy is generated from the breakdown of complex substances into simpler ones (mitochondrial oxidation). Because this enzyme occurs at the very end of the fatty acid oxidation pathway, the compounds that accumulate can be utilized by other enzymes, preventing clinical symptoms from occurring.More than 100 different mutations in the ACADS gene cause SCADD. Two common variations (polymorphisms) have also been found in the ACADS gene. It has been suggested that SCAD deficiency may be a risk factor that can make other neuromuscular disorders worse, but this remains unproven. 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 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. All individuals carry a few 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.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_3
|
Affects of Short Chain Acyl CoA Dehydrogenase Deficiency
|
SCAD deficiency is thought to affect 1 in 40,000 to 100,000 newborns. In the US, ~10% of individuals have two copies of one of the common polymorphisms leading to potential identification of related metabolites in urine or blood.
|
Affects of Short Chain Acyl CoA Dehydrogenase Deficiency. SCAD deficiency is thought to affect 1 in 40,000 to 100,000 newborns. In the US, ~10% of individuals have two copies of one of the common polymorphisms leading to potential identification of related metabolites in urine or blood.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_4
|
Related disorders of Short Chain Acyl CoA Dehydrogenase Deficiency
|
The following disorders can have similar lab findings to those seen SCADD and therefore should be considered when symptoms are present. Comparisons may be useful for a differential diagnosis:Mitochondrial respiratory chain disorders are a group of related disorders characterized by mutations affecting the parts of the cell that release energy (mitochondria). Mitochondrial disorders often hamper the ability of affected cells to combine food with oxygen to produce energy. In most mitochondrial disorders, abnormally high numbers of defective mitochondria are present in the cells of the body. Mitochondrial diseases often affect more than one organ system of the body. Common symptoms associated with mitochondrial disorders include muscle weakness, stroke-like episodes, and seizures. Exercise intolerance is another common symptom. Some forms are associated with disease of the heart muscle (cardiomyopathy). Mitochondrial disorders include Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, NARP, and Leber hereditary optic neuropathy. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.) Ethylmalonic acid (EMA) is elevated in both mitochondrial respiratory chain disorders and SCADD.Ethylmaloninc encephalopathy is another disorder of mitochondrial metabolism caused by mutations in the ETHE1 gene. Symptoms include lactic acid build up in the blood, seizures, and platelet gastrointestinal dysfunction. EMA is elevated in this disorder, though typically higher than in SCADD
|
Related disorders of Short Chain Acyl CoA Dehydrogenase Deficiency. The following disorders can have similar lab findings to those seen SCADD and therefore should be considered when symptoms are present. Comparisons may be useful for a differential diagnosis:Mitochondrial respiratory chain disorders are a group of related disorders characterized by mutations affecting the parts of the cell that release energy (mitochondria). Mitochondrial disorders often hamper the ability of affected cells to combine food with oxygen to produce energy. In most mitochondrial disorders, abnormally high numbers of defective mitochondria are present in the cells of the body. Mitochondrial diseases often affect more than one organ system of the body. Common symptoms associated with mitochondrial disorders include muscle weakness, stroke-like episodes, and seizures. Exercise intolerance is another common symptom. Some forms are associated with disease of the heart muscle (cardiomyopathy). Mitochondrial disorders include Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, NARP, and Leber hereditary optic neuropathy. (For more information on this disorder, choose the specific disorder name as your search term in the Rare Disease Database.) Ethylmalonic acid (EMA) is elevated in both mitochondrial respiratory chain disorders and SCADD.Ethylmaloninc encephalopathy is another disorder of mitochondrial metabolism caused by mutations in the ETHE1 gene. Symptoms include lactic acid build up in the blood, seizures, and platelet gastrointestinal dysfunction. EMA is elevated in this disorder, though typically higher than in SCADD
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_5
|
Diagnosis of Short Chain Acyl CoA Dehydrogenase Deficiency
|
Diagnosis of SCADD should be suspected on the basis of elevated ethylmalonic acid (EMA) excretion in urine or butyrylcarnitine (C4 carnitine) in blood. Patients with this finding should have whole gene sequencing. If a mutation is not identified and EMA excretion is persistent, additional clinical evaluation is warranted as another diagnosis is likely. The presence of the common polymorphisms generally leads to reduction of muscle SCAD activity to 50-67% of normal; rarely, patients with no other identifiable mutations have had complete loss of activity. However, there is little or no clinical utility in measuring enzyme activity and muscle biopsy is not recommended to diagnosis SCAD deficiency.As noted above, expanded newborn screening with tandem mass spectrometry is identifying more infants with SCADD than in the past. Adjustment of the screening results interpretation can usually differentiate between individuals having the common polymorphisms vs. complete SCADD.
|
Diagnosis of Short Chain Acyl CoA Dehydrogenase Deficiency. Diagnosis of SCADD should be suspected on the basis of elevated ethylmalonic acid (EMA) excretion in urine or butyrylcarnitine (C4 carnitine) in blood. Patients with this finding should have whole gene sequencing. If a mutation is not identified and EMA excretion is persistent, additional clinical evaluation is warranted as another diagnosis is likely. The presence of the common polymorphisms generally leads to reduction of muscle SCAD activity to 50-67% of normal; rarely, patients with no other identifiable mutations have had complete loss of activity. However, there is little or no clinical utility in measuring enzyme activity and muscle biopsy is not recommended to diagnosis SCAD deficiency.As noted above, expanded newborn screening with tandem mass spectrometry is identifying more infants with SCADD than in the past. Adjustment of the screening results interpretation can usually differentiate between individuals having the common polymorphisms vs. complete SCADD.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1113_6
|
Therapies of Short Chain Acyl CoA Dehydrogenase Deficiency
|
TreatmentThere is no need to treat SCADD.Genetic counseling is recommended for patients and their families.
|
Therapies of Short Chain Acyl CoA Dehydrogenase Deficiency. TreatmentThere is no need to treat SCADD.Genetic counseling is recommended for patients and their families.
| 1,113 |
Short Chain Acyl CoA Dehydrogenase Deficiency
|
nord_1114_0
|
Overview of Short QT Syndrome
|
SummaryShort QT syndrome (SQTS) is an extremely rare but life-threatening familial disorder characterized by an abnormally short QT interval on the electrocardiogram (ECG), indicating that the heart muscle takes less time than usual to recharge between beats. SQTS increases the risk of an abnormal rate or rhythm of the heartbeat (cardiac arrhythmia), and sudden cardiac death (SCD). SQTS is a “channelopathy” caused by changes (mutations) in genes encoding proteins forming potassium or calcium ion channels (pores) on the cardiac, and even neuronal, cell membranes that are essential for the heart’s electro-mechanical function. The syndrome was first identified in 2000; since then, only about 250 cases have been reported in the scientific literature. Families with SQTS usually have incomplete penetrance, which means that children of an affected parent who inherit the gene mutation may or may not develop the disease. The specific symptoms, onset of symptoms and severity vary from one sibling to another. Accordingly, although SQTS may be diagnosed in children if they show clear cardiac symptoms, or if family history is suspected, it is difficult to establish a specific age of onset. Consequently, the incidence of SQTS in the general population remains unclear. In cases in which the genetic cause is known (20-30% of cases) the mutation is inherited in an autosomal dominant manner. However, the mechanisms that link the gene mutation to the arrhythmias and SCD are unknown, and the treatment depends on the signs and symptoms in each individual patient.IntroductionShort QT syndrome (SQTS) receives its specific name because on the electrocardiogram (ECG), its main characteristic is the presence of an abnormally short QT interval. The ECG is widely used by cardiologists to diagnose heart rhythm and conduction problems associated with cardiovascular conditions. Every time the heart beats, electrical currents flow through it, the ECG records the changes in voltage associated with such currents versus time. By placing electrodes at specific locations of the body surface and connecting them to an ECG machine, an expert can identify a wide variety of cardiac alterations, including abnormal heart rate and rhythm. Normally on ECG, each beat is composed by specific voltage waves, labelled P, Q, R, S and T, and organized as complexes, segments, and intervals with known amplitudes and durations. They indicate the local excitation and recovery as the electrical wave moves from the atria to the ventricles of the heart. The P wave represents the excitation (depolarization) of the atria; the QRS complex represents the depolarization of the ventricles and the T wave indicates the recovery (repolarization) from ventricular excitation. The time interval between the onset of the QRS and the end of the T wave is the QT interval. In humans, the QT interval normally lasts between 0.35 and 0.45 seconds, which is optimal to allow the ventricles to contract and pump the blood to the rest of the body. Since the QT interval normally varies depending on the heart rate, a mathematical formula is used to correct the QT interval (QTc) for changes in this parameter. In patients with SQTS, ventricular repolarization occurs too early and consequently, their QT interval will be too brief. Nowadays, a QTc interval less than 0.34 seconds is sufficient to suspect SQTS.Although the link between a short QT interval and SCD had previously been suspected, Gussak, I. et al. described the SQTS in 2000 in a family with abnormally short QTc and other cardiac complications. Thereafter, SQTS was considered a new clinical entity associated with cardiac arrhythmia and increased risk of SCD but unknown mechanism. The long QT syndrome (LQTS), another channelopathy in which patients have a QTc interval longer than 0.45 seconds, was described several years earlier and its genetic basis was already known to be associated with mutations in genes for sodium, potassium and calcium ion channel proteins. Hence, investigators theorized that perhaps mutations provoking SQTS, while different from LQTS, could occur in the same or related genes. The first time SQTS was linked to a genetic cause was in 2004, when Brugada, R. et al. screened candidate genes encoding ion channels contributing to the repolarization phase of the cellular equivalent of the QT interval, the ventricular action potential. They identified a mutation in KCNH2, the gene coding the membrane potassium channel HERG responsible for positive repolarizing current, in two families with history of short QTc interval, arrhythmias and SCD. However, with time, it has become apparent that SQTS is a genetic disease caused by mutations in several different genes. Much effort has been devoted since then to the study of the causes of SQTS to include these genes in genetic screening panels with the aim of getting an early and appropriate diagnosis.
|
Overview of Short QT Syndrome. SummaryShort QT syndrome (SQTS) is an extremely rare but life-threatening familial disorder characterized by an abnormally short QT interval on the electrocardiogram (ECG), indicating that the heart muscle takes less time than usual to recharge between beats. SQTS increases the risk of an abnormal rate or rhythm of the heartbeat (cardiac arrhythmia), and sudden cardiac death (SCD). SQTS is a “channelopathy” caused by changes (mutations) in genes encoding proteins forming potassium or calcium ion channels (pores) on the cardiac, and even neuronal, cell membranes that are essential for the heart’s electro-mechanical function. The syndrome was first identified in 2000; since then, only about 250 cases have been reported in the scientific literature. Families with SQTS usually have incomplete penetrance, which means that children of an affected parent who inherit the gene mutation may or may not develop the disease. The specific symptoms, onset of symptoms and severity vary from one sibling to another. Accordingly, although SQTS may be diagnosed in children if they show clear cardiac symptoms, or if family history is suspected, it is difficult to establish a specific age of onset. Consequently, the incidence of SQTS in the general population remains unclear. In cases in which the genetic cause is known (20-30% of cases) the mutation is inherited in an autosomal dominant manner. However, the mechanisms that link the gene mutation to the arrhythmias and SCD are unknown, and the treatment depends on the signs and symptoms in each individual patient.IntroductionShort QT syndrome (SQTS) receives its specific name because on the electrocardiogram (ECG), its main characteristic is the presence of an abnormally short QT interval. The ECG is widely used by cardiologists to diagnose heart rhythm and conduction problems associated with cardiovascular conditions. Every time the heart beats, electrical currents flow through it, the ECG records the changes in voltage associated with such currents versus time. By placing electrodes at specific locations of the body surface and connecting them to an ECG machine, an expert can identify a wide variety of cardiac alterations, including abnormal heart rate and rhythm. Normally on ECG, each beat is composed by specific voltage waves, labelled P, Q, R, S and T, and organized as complexes, segments, and intervals with known amplitudes and durations. They indicate the local excitation and recovery as the electrical wave moves from the atria to the ventricles of the heart. The P wave represents the excitation (depolarization) of the atria; the QRS complex represents the depolarization of the ventricles and the T wave indicates the recovery (repolarization) from ventricular excitation. The time interval between the onset of the QRS and the end of the T wave is the QT interval. In humans, the QT interval normally lasts between 0.35 and 0.45 seconds, which is optimal to allow the ventricles to contract and pump the blood to the rest of the body. Since the QT interval normally varies depending on the heart rate, a mathematical formula is used to correct the QT interval (QTc) for changes in this parameter. In patients with SQTS, ventricular repolarization occurs too early and consequently, their QT interval will be too brief. Nowadays, a QTc interval less than 0.34 seconds is sufficient to suspect SQTS.Although the link between a short QT interval and SCD had previously been suspected, Gussak, I. et al. described the SQTS in 2000 in a family with abnormally short QTc and other cardiac complications. Thereafter, SQTS was considered a new clinical entity associated with cardiac arrhythmia and increased risk of SCD but unknown mechanism. The long QT syndrome (LQTS), another channelopathy in which patients have a QTc interval longer than 0.45 seconds, was described several years earlier and its genetic basis was already known to be associated with mutations in genes for sodium, potassium and calcium ion channel proteins. Hence, investigators theorized that perhaps mutations provoking SQTS, while different from LQTS, could occur in the same or related genes. The first time SQTS was linked to a genetic cause was in 2004, when Brugada, R. et al. screened candidate genes encoding ion channels contributing to the repolarization phase of the cellular equivalent of the QT interval, the ventricular action potential. They identified a mutation in KCNH2, the gene coding the membrane potassium channel HERG responsible for positive repolarizing current, in two families with history of short QTc interval, arrhythmias and SCD. However, with time, it has become apparent that SQTS is a genetic disease caused by mutations in several different genes. Much effort has been devoted since then to the study of the causes of SQTS to include these genes in genetic screening panels with the aim of getting an early and appropriate diagnosis.
| 1,114 |
Short QT Syndrome
|
nord_1114_1
|
Symptoms of Short QT Syndrome
|
The extremely abbreviated QTc interval that characterizes the ECG of SQTS patients is associated with defects in cardiac electrical function including life-threatening arrhythmias that may appear at rest or during exercise with no apparent initiating cause. The median age of appearance is 30 years, though it ranges widely, from a few months to 60 years of life. Moreover, the clinical presentation of the syndrome is diverse due to its variable expressivity even among members of the same family. Nevertheless, in up to 20% of patients, the first symptoms are usually: cardiac arrest (up to 40%), palpitations (30%) and syncope (25%). Atrial fibrillation has been reported in up to 80% of SQTS patients including children, adolescents and young adults. However, frequently, ventricular fibrillation and SCD can be the first manifestation, a fatal event that may have devastating impact on the families and the community. Moreover, since some of the ionic channels related to SQTS are also present in neurons, there are subtypes of SQTS that include epilepsy and autism as well.All the above signs of the syndrome are associated with a QTc interval briefer than 0.34 seconds in patients with structurally normal hearts, but the precise link between the electrical abnormality and the fatal event has not been established.
|
Symptoms of Short QT Syndrome. The extremely abbreviated QTc interval that characterizes the ECG of SQTS patients is associated with defects in cardiac electrical function including life-threatening arrhythmias that may appear at rest or during exercise with no apparent initiating cause. The median age of appearance is 30 years, though it ranges widely, from a few months to 60 years of life. Moreover, the clinical presentation of the syndrome is diverse due to its variable expressivity even among members of the same family. Nevertheless, in up to 20% of patients, the first symptoms are usually: cardiac arrest (up to 40%), palpitations (30%) and syncope (25%). Atrial fibrillation has been reported in up to 80% of SQTS patients including children, adolescents and young adults. However, frequently, ventricular fibrillation and SCD can be the first manifestation, a fatal event that may have devastating impact on the families and the community. Moreover, since some of the ionic channels related to SQTS are also present in neurons, there are subtypes of SQTS that include epilepsy and autism as well.All the above signs of the syndrome are associated with a QTc interval briefer than 0.34 seconds in patients with structurally normal hearts, but the precise link between the electrical abnormality and the fatal event has not been established.
| 1,114 |
Short QT Syndrome
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.