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nord_542_6 | Therapies of Growth Hormone Deficiency | Treatment
When a diagnosis of GHD is made, treatment may then be initiated. Children with GHD should be started on recombinant human growth hormone as soon as the disorder is recognized to optimize growth potential. The dosage is gradually increased to its highest dose during puberty, and discontinued at or near completion of skeletal maturation when the patient may require retesting to see if GH is needed as an adult.The FDA has approved the use of somatropin (Nutropin [Genentech)] Humatrope [Lilly], Genotropin [Pfizer], Saizen [EMD Serono], Norditropin [Novo Nordisk], Tev-Tropin [Teva], and Omnitrope [Sandoz] for the treatment of growth hormone deficiency. | Therapies of Growth Hormone Deficiency. Treatment
When a diagnosis of GHD is made, treatment may then be initiated. Children with GHD should be started on recombinant human growth hormone as soon as the disorder is recognized to optimize growth potential. The dosage is gradually increased to its highest dose during puberty, and discontinued at or near completion of skeletal maturation when the patient may require retesting to see if GH is needed as an adult.The FDA has approved the use of somatropin (Nutropin [Genentech)] Humatrope [Lilly], Genotropin [Pfizer], Saizen [EMD Serono], Norditropin [Novo Nordisk], Tev-Tropin [Teva], and Omnitrope [Sandoz] for the treatment of growth hormone deficiency. | 542 | Growth Hormone Deficiency |
nord_543_0 | Overview of Growth Hormone Insensitivity | SummaryGrowth hormone insensitivity (GHI) is a group of extremely rare genetic disorders in which the body is unable to use the growth hormone that it produces. GHI can be caused by mutations in the growth hormone receptor (GHR) gene or mutations in genes involved in the action pathway within the cell after growth hormone binds to its receptor, preventing production of insulin-like growth factor (IGF-1), the substance responsible for the growth effects of growth hormone. Even more rarely, children with a GH gene deletion who have been treated with recombinant GH develop antibodies that block GH binding to its receptor. Affected children fail to grow normally.Children with GHRD who are treated with IGF-1 before puberty have improved growth, but, unlike children with GH deficiency given recombinant GH treatment, they do not have normal growth restored. Treatment for these conditions is only effective while the growing bones are still open, i.e. before the completion of adolescence. IGF-I insensitivity due to IGF-I receptor mutation mimics GHI, but results in less severe growth deficiency and is somewhat responsive to treatment with recombinant GH.GHI is characterized by short stature and delayed bone age, as well as normal or high levels of circulating GH. Other common symptoms are delayed onset of puberty, prominent forehead, low blood sugar in infancy and early childhood, and obesity in adulthood. Except for an extremely rare form of GHI, where the gene for IGF-I is defective, brain development is normal, apparently because IGF-I can be made during fetal life without GH stimulation in the other conditions. Some, but definitely not all, patients with the less rare condition of IGF-I receptor deficiency may have mild intellectual impairment.IntroductionLaron and colleagues in Israel, first reported GHRD in 1966, based on observations that began in 1958, and have continued to the present. The molecular basis for the syndrome they described, a mutation of the GHR gene in some of the Israeli patients was initially described in 1989, and since then over 60 different mutations in the gene for this protein has been identified by many investigators. Mutations in genes in the action pathway of GH after it’s binding to the GHR and associated with varying effects of IGF-I deficiency have been described in the past 15 years. | Overview of Growth Hormone Insensitivity. SummaryGrowth hormone insensitivity (GHI) is a group of extremely rare genetic disorders in which the body is unable to use the growth hormone that it produces. GHI can be caused by mutations in the growth hormone receptor (GHR) gene or mutations in genes involved in the action pathway within the cell after growth hormone binds to its receptor, preventing production of insulin-like growth factor (IGF-1), the substance responsible for the growth effects of growth hormone. Even more rarely, children with a GH gene deletion who have been treated with recombinant GH develop antibodies that block GH binding to its receptor. Affected children fail to grow normally.Children with GHRD who are treated with IGF-1 before puberty have improved growth, but, unlike children with GH deficiency given recombinant GH treatment, they do not have normal growth restored. Treatment for these conditions is only effective while the growing bones are still open, i.e. before the completion of adolescence. IGF-I insensitivity due to IGF-I receptor mutation mimics GHI, but results in less severe growth deficiency and is somewhat responsive to treatment with recombinant GH.GHI is characterized by short stature and delayed bone age, as well as normal or high levels of circulating GH. Other common symptoms are delayed onset of puberty, prominent forehead, low blood sugar in infancy and early childhood, and obesity in adulthood. Except for an extremely rare form of GHI, where the gene for IGF-I is defective, brain development is normal, apparently because IGF-I can be made during fetal life without GH stimulation in the other conditions. Some, but definitely not all, patients with the less rare condition of IGF-I receptor deficiency may have mild intellectual impairment.IntroductionLaron and colleagues in Israel, first reported GHRD in 1966, based on observations that began in 1958, and have continued to the present. The molecular basis for the syndrome they described, a mutation of the GHR gene in some of the Israeli patients was initially described in 1989, and since then over 60 different mutations in the gene for this protein has been identified by many investigators. Mutations in genes in the action pathway of GH after it’s binding to the GHR and associated with varying effects of IGF-I deficiency have been described in the past 15 years. | 543 | Growth Hormone Insensitivity |
nord_543_1 | Symptoms of Growth Hormone Insensitivity | There is a wide range of effects depending on the gene mutations involved (see Causes section). The very few individuals with IGF-I gene mutation have severe intellectual disability and intrauterine growth failure, with deafness and micrognathia. GHRD results in severe growth failure without deleterious effects on intrauterine growth or brain development, and the mutation of STAT5b, responsible for an important activator protein, has similar growth effects but is also associated with severe impairment of immunocompetence. The IGFALS mutation, affecting an important stabilizing component of the circulating IGF-I, while associated with very low circulating IGF levels, has only modest effects on growth.GHI is characterized by severe but proportionate short stature as a result of growth failure that begins at birth. Along with growth retardation, there are delays in tooth eruption. There is also disproportion between the growth of the skull and face, a saddle nose and deep-set eyes. Sexual development is moderately delayed in both genders. In females with these disorders, the onset of menses usually takes place between 16 to 19 years of age. Hands and feet are smaller than normal, in proportion to overall body size. A high-pitched voice may also be present and obesity is common in the adults, especially women.High circulating levels of GH are found in the children but may not be obvious without stimulation tests in the adults. A high percentage of young patients have low blood sugar levels (hypoglycemia) that can be associated with seizures in some very young children. Recently, researchers have found that a population of individuals with GHRD in Ecuador (where approximately 1/3 of the world’s population of GHRD has been identified) had absence of cancer and diabetes with molecular evidence of protection from aging changes in their DNA. This may be due to a protective effect from the low IGF-I levels, and in the case of absence of diabetes despite obesity, due to absence of counter-regulation effects of GH. | Symptoms of Growth Hormone Insensitivity. There is a wide range of effects depending on the gene mutations involved (see Causes section). The very few individuals with IGF-I gene mutation have severe intellectual disability and intrauterine growth failure, with deafness and micrognathia. GHRD results in severe growth failure without deleterious effects on intrauterine growth or brain development, and the mutation of STAT5b, responsible for an important activator protein, has similar growth effects but is also associated with severe impairment of immunocompetence. The IGFALS mutation, affecting an important stabilizing component of the circulating IGF-I, while associated with very low circulating IGF levels, has only modest effects on growth.GHI is characterized by severe but proportionate short stature as a result of growth failure that begins at birth. Along with growth retardation, there are delays in tooth eruption. There is also disproportion between the growth of the skull and face, a saddle nose and deep-set eyes. Sexual development is moderately delayed in both genders. In females with these disorders, the onset of menses usually takes place between 16 to 19 years of age. Hands and feet are smaller than normal, in proportion to overall body size. A high-pitched voice may also be present and obesity is common in the adults, especially women.High circulating levels of GH are found in the children but may not be obvious without stimulation tests in the adults. A high percentage of young patients have low blood sugar levels (hypoglycemia) that can be associated with seizures in some very young children. Recently, researchers have found that a population of individuals with GHRD in Ecuador (where approximately 1/3 of the world’s population of GHRD has been identified) had absence of cancer and diabetes with molecular evidence of protection from aging changes in their DNA. This may be due to a protective effect from the low IGF-I levels, and in the case of absence of diabetes despite obesity, due to absence of counter-regulation effects of GH. | 543 | Growth Hormone Insensitivity |
nord_543_2 | Causes of Growth Hormone Insensitivity | GHI is inherited as an autosomal recessive genetic disorder and caused by mutation of the GHR gene or mutations in the genes involved in the action pathway within the cell after GH binds to its receptor, including STAT5b, IGF-1, and IGFALS.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. 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 Growth Hormone Insensitivity. GHI is inherited as an autosomal recessive genetic disorder and caused by mutation of the GHR gene or mutations in the genes involved in the action pathway within the cell after GH binds to its receptor, including STAT5b, IGF-1, and IGFALS.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. 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. | 543 | Growth Hormone Insensitivity |
nord_543_3 | Affects of Growth Hormone Insensitivity | Worldwide, only about 300 cases of GHI due to GHRD have been reported. The ethnic background for most (90%) of the reported cases is known. About 65% of patients have Middle Eastern ancestry and a group of Ecuadorian conversos. (Conversos are Jews who converted to Christianity in Spain during the Inquisition, some of whom migrated to the New World) Subsequently, marriage among close relatives made the disorder more common among the descendants of these groups. STAT5b, IGF-1 and IGFALS mutations have been reported in only a few families. | Affects of Growth Hormone Insensitivity. Worldwide, only about 300 cases of GHI due to GHRD have been reported. The ethnic background for most (90%) of the reported cases is known. About 65% of patients have Middle Eastern ancestry and a group of Ecuadorian conversos. (Conversos are Jews who converted to Christianity in Spain during the Inquisition, some of whom migrated to the New World) Subsequently, marriage among close relatives made the disorder more common among the descendants of these groups. STAT5b, IGF-1 and IGFALS mutations have been reported in only a few families. | 543 | Growth Hormone Insensitivity |
nord_543_4 | Related disorders of Growth Hormone Insensitivity | Symptoms of the following disorders can be similar to those of GHI. Comparisons may be useful for a differential diagnosis:In addition to the genetic forms of GHI, failure to have a normal growth response despite adequate GH production is characteristic of a number of conditions including chronic illness, undernutrition, kidney disease, liver disease, and congenital syndromes. These conditions are often referred to as secondary GHI.Coffin-Siris syndrome is a disorder of unknown cause. It is present at birth and affects both sexes. It is chiefly characterized by feeding problems, frequent respiratory infections, and growth deficiencies. (For more information on this disorder, choose “Coffin-Siris” as your search term in the Rare Disease Database.)Cockayne syndrome is a progressive disorder which manifests itself during the second year of life. It is characterized by a hypersensitivity to sunlight and growth retardation. (For more information on this disorder, choose “Cockayne” as your search term in the Rare Disease Database.)Growth hormone deficiency (GHD), in its most severe form, is very similar to primary GHI, the main difference being that in children with GHI, a high level of GH is present in the blood and the administration of recombinant GH does not result in normalization of growth. The cause of GHD is often unknown, but genetic defects have been described in the receptor for GH releasing hormone from the brain and in the GH molecule, as well as in factors that lead to other hormone deficiencies along with GH. It can be treated fairly easily and reliably with injections of recombinant human GH. (For more information on this disorder, choose “growth hormone deficiency” as your search term in the Rare Disease Database.)Hydrocephalus can be confused with GHI due to GHRD in infancy because of the prominence of the forehead, presence of sclera (white) above the iris of the eye, the so-called “setting sun sign”, the small face relative to the skull, and the prominence of scalp veins. However, rapid head growth is not occurring as it is in hydrocephalus. (For more information on this disorder, choose “Hydrocephalus” as your search term in the Rare Disease Database.)There are many disorders that can cause short stature. For more information on those disorders contact the Human Growth Foundation or the MAGIC Foundation noted in the resources section of this report. | Related disorders of Growth Hormone Insensitivity. Symptoms of the following disorders can be similar to those of GHI. Comparisons may be useful for a differential diagnosis:In addition to the genetic forms of GHI, failure to have a normal growth response despite adequate GH production is characteristic of a number of conditions including chronic illness, undernutrition, kidney disease, liver disease, and congenital syndromes. These conditions are often referred to as secondary GHI.Coffin-Siris syndrome is a disorder of unknown cause. It is present at birth and affects both sexes. It is chiefly characterized by feeding problems, frequent respiratory infections, and growth deficiencies. (For more information on this disorder, choose “Coffin-Siris” as your search term in the Rare Disease Database.)Cockayne syndrome is a progressive disorder which manifests itself during the second year of life. It is characterized by a hypersensitivity to sunlight and growth retardation. (For more information on this disorder, choose “Cockayne” as your search term in the Rare Disease Database.)Growth hormone deficiency (GHD), in its most severe form, is very similar to primary GHI, the main difference being that in children with GHI, a high level of GH is present in the blood and the administration of recombinant GH does not result in normalization of growth. The cause of GHD is often unknown, but genetic defects have been described in the receptor for GH releasing hormone from the brain and in the GH molecule, as well as in factors that lead to other hormone deficiencies along with GH. It can be treated fairly easily and reliably with injections of recombinant human GH. (For more information on this disorder, choose “growth hormone deficiency” as your search term in the Rare Disease Database.)Hydrocephalus can be confused with GHI due to GHRD in infancy because of the prominence of the forehead, presence of sclera (white) above the iris of the eye, the so-called “setting sun sign”, the small face relative to the skull, and the prominence of scalp veins. However, rapid head growth is not occurring as it is in hydrocephalus. (For more information on this disorder, choose “Hydrocephalus” as your search term in the Rare Disease Database.)There are many disorders that can cause short stature. For more information on those disorders contact the Human Growth Foundation or the MAGIC Foundation noted in the resources section of this report. | 543 | Growth Hormone Insensitivity |
nord_543_5 | Diagnosis of Growth Hormone Insensitivity | A diagnosis of GHI is usually made when failure to grow is accompanied by the typical facial appearance and central chubbiness that suggests GH deficiency, but with the finding of elevated GH levels. | Diagnosis of Growth Hormone Insensitivity. A diagnosis of GHI is usually made when failure to grow is accompanied by the typical facial appearance and central chubbiness that suggests GH deficiency, but with the finding of elevated GH levels. | 543 | Growth Hormone Insensitivity |
nord_543_6 | Therapies of Growth Hormone Insensitivity | TreatmentThe orphan drug mecasermin rinfabate (recombinant IGF-I) has been approved for children whose growth failure is due to GHRD or GH inactivating antibodies. For more information contact:Ipsen Biopharmaceuticals
Basking Ridge, NJ
http://increlex.com/patient-patient-product-information.aspTreatment of GHI with recombinant human GH is not effective because the body cannot utilize the hormone to grow. Recombinant IGF-I therapy is associated with a risk of hypoglycemia which can be prevented by feeding. Fortunately, long-term effects of hypoglycemia have not been seen.Genetic counseling is recommended for patients and their families. | Therapies of Growth Hormone Insensitivity. TreatmentThe orphan drug mecasermin rinfabate (recombinant IGF-I) has been approved for children whose growth failure is due to GHRD or GH inactivating antibodies. For more information contact:Ipsen Biopharmaceuticals
Basking Ridge, NJ
http://increlex.com/patient-patient-product-information.aspTreatment of GHI with recombinant human GH is not effective because the body cannot utilize the hormone to grow. Recombinant IGF-I therapy is associated with a risk of hypoglycemia which can be prevented by feeding. Fortunately, long-term effects of hypoglycemia have not been seen.Genetic counseling is recommended for patients and their families. | 543 | Growth Hormone Insensitivity |
nord_544_0 | Overview of Guanidinoacetate Methyltransferase Deficiency | Summary
Guanidinoacetate methyltransferase deficiency (GAMT) is one of the three cerebral creatine deficiency syndromes (CCDS). These conditions are inborn errors of creatine metabolism which interrupt the formation or transport of creatine. Creatine is necessary to use energy derived from adenosine triphosphate (ATP), which provides energy to all cells in the body. Creatine is essential to sustain the high energy levels needed for muscle and brain development. The onset of GAMT symptoms occurs between ages 3 months and 3 years of age. | Overview of Guanidinoacetate Methyltransferase Deficiency. Summary
Guanidinoacetate methyltransferase deficiency (GAMT) is one of the three cerebral creatine deficiency syndromes (CCDS). These conditions are inborn errors of creatine metabolism which interrupt the formation or transport of creatine. Creatine is necessary to use energy derived from adenosine triphosphate (ATP), which provides energy to all cells in the body. Creatine is essential to sustain the high energy levels needed for muscle and brain development. The onset of GAMT symptoms occurs between ages 3 months and 3 years of age. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_1 | Symptoms of Guanidinoacetate Methyltransferase Deficiency | The severity of GAMT varies from patient to patient. Global developmental delays affect all individuals with this disorder and may be the first sign, appearing before other symptoms. Most individuals with GAMT deficiency have intellectual disabilities, seizure disorders, muscle weakness, behavior disorders and movement disorders. People with GAMT may have weak muscle tone and delayed development of motor skills such as sitting or walking. Severely affected patients may lose previously acquired skills such as the ability to support their head or to sit unsupported. | Symptoms of Guanidinoacetate Methyltransferase Deficiency. The severity of GAMT varies from patient to patient. Global developmental delays affect all individuals with this disorder and may be the first sign, appearing before other symptoms. Most individuals with GAMT deficiency have intellectual disabilities, seizure disorders, muscle weakness, behavior disorders and movement disorders. People with GAMT may have weak muscle tone and delayed development of motor skills such as sitting or walking. Severely affected patients may lose previously acquired skills such as the ability to support their head or to sit unsupported. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_2 | Causes of Guanidinoacetate Methyltransferase Deficiency | GAMT deficiency is a caused by changes (called variants or mutations) in the GAMT gene that makes the enzyme that creates creatine, resulting in a shortage of creatine. It is the most severe of the three CCDS due to the elevation of guanidinoacetate (which is neurotoxic) in addition to creatine deficiency. Affected individuals may demonstrate cerebral creatine deficiency on MR spectroscopy and high GAA in plasma.The inheritance pattern for GAMT is autosomal recessive. 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. | Causes of Guanidinoacetate Methyltransferase Deficiency. GAMT deficiency is a caused by changes (called variants or mutations) in the GAMT gene that makes the enzyme that creates creatine, resulting in a shortage of creatine. It is the most severe of the three CCDS due to the elevation of guanidinoacetate (which is neurotoxic) in addition to creatine deficiency. Affected individuals may demonstrate cerebral creatine deficiency on MR spectroscopy and high GAA in plasma.The inheritance pattern for GAMT is autosomal recessive. 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. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_3 | Affects of Guanidinoacetate Methyltransferase Deficiency | The prevalence of GAMT deficiency has been estimated to be from 1 out of 250,000 to 1 out of 550,000 patients being diagnosed. As of 2015, there have only been 110 individuals with GAMT deficiency diagnosed worldwide. | Affects of Guanidinoacetate Methyltransferase Deficiency. The prevalence of GAMT deficiency has been estimated to be from 1 out of 250,000 to 1 out of 550,000 patients being diagnosed. As of 2015, there have only been 110 individuals with GAMT deficiency diagnosed worldwide. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_4 | Related disorders of Guanidinoacetate Methyltransferase Deficiency | GAMT deficiency patients are frequently misdiagnosed with cerebral palsy as infants and toddlers. Children are often misdiagnosed with autism or global developmental delays. | Related disorders of Guanidinoacetate Methyltransferase Deficiency. GAMT deficiency patients are frequently misdiagnosed with cerebral palsy as infants and toddlers. Children are often misdiagnosed with autism or global developmental delays. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_5 | Diagnosis of Guanidinoacetate Methyltransferase Deficiency | Testing in both urine and plasma is recommended by measuring the concentration of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn). A positive screen for GAMT is based on plasma GAA that is elevated with creatine being low and urine GAA that is elevated and creatine being low to normal. Urine testing might be normal in young children, for which plasma testing is recommended.Follow up genomic testing for mutations in the GAMT gene may be ordered along with brain MRI with spectroscopy to confirm GAMT diagnosis. MRI with spectroscopy is useful for measuring creatine levels in the brain.Generally not required for diagnosis, but cultured skin fibroblasts for enzyme assay may be helpful when gene sequencing test results are unclear.GAMT deficiency was recommended for inclusion in the Recommended Uniform Screening Panel for newborns in 2022, but it is still unclear when individual states will adopt it. | Diagnosis of Guanidinoacetate Methyltransferase Deficiency. Testing in both urine and plasma is recommended by measuring the concentration of creatine (Cr), guanidinoacetate (GAA), and creatinine (Crn). A positive screen for GAMT is based on plasma GAA that is elevated with creatine being low and urine GAA that is elevated and creatine being low to normal. Urine testing might be normal in young children, for which plasma testing is recommended.Follow up genomic testing for mutations in the GAMT gene may be ordered along with brain MRI with spectroscopy to confirm GAMT diagnosis. MRI with spectroscopy is useful for measuring creatine levels in the brain.Generally not required for diagnosis, but cultured skin fibroblasts for enzyme assay may be helpful when gene sequencing test results are unclear.GAMT deficiency was recommended for inclusion in the Recommended Uniform Screening Panel for newborns in 2022, but it is still unclear when individual states will adopt it. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_544_6 | Therapies of Guanidinoacetate Methyltransferase Deficiency | Treatment
Individuals diagnosed with GAMT may require the coordinated efforts of a team of specialists. A pediatrician or an adult primary care physician, neurologist, geneticist, dietician and a doctor who is familiar with metabolic disorders may need to work together to ensure a comprehensive approach to treatment. Occupational, speech, and physical therapists may be necessary to treat developmental disabilities and behavior therapy to address behavior problems.Treatments vary with each GAMT patient. Oral supplementation is available and effective if initiated early in life.Oral creatine monohydrate is given to replenish creatine levels in the brain and other tissues in individuals with GAMT. A low arginine/protein diet, L-ornithine supplementation, and sodium benzoate are used to reduce toxic levels of guanidinoacetate in individuals with GAMT deficiency. For GAMT patients being treated with creatine monohydrate, a routine measurement of renal function should be considered to detect possible creatine-associated kidney disease (nephropathy).Prevention of Primary Symptoms
Early treatment at the first sign of symptoms in patients with GAMT is effective in improving patient’s quality of life. The treatment in newborn siblings of individuals with GAMT has been shown to prevent disease manifestation. | Therapies of Guanidinoacetate Methyltransferase Deficiency. Treatment
Individuals diagnosed with GAMT may require the coordinated efforts of a team of specialists. A pediatrician or an adult primary care physician, neurologist, geneticist, dietician and a doctor who is familiar with metabolic disorders may need to work together to ensure a comprehensive approach to treatment. Occupational, speech, and physical therapists may be necessary to treat developmental disabilities and behavior therapy to address behavior problems.Treatments vary with each GAMT patient. Oral supplementation is available and effective if initiated early in life.Oral creatine monohydrate is given to replenish creatine levels in the brain and other tissues in individuals with GAMT. A low arginine/protein diet, L-ornithine supplementation, and sodium benzoate are used to reduce toxic levels of guanidinoacetate in individuals with GAMT deficiency. For GAMT patients being treated with creatine monohydrate, a routine measurement of renal function should be considered to detect possible creatine-associated kidney disease (nephropathy).Prevention of Primary Symptoms
Early treatment at the first sign of symptoms in patients with GAMT is effective in improving patient’s quality of life. The treatment in newborn siblings of individuals with GAMT has been shown to prevent disease manifestation. | 544 | Guanidinoacetate Methyltransferase Deficiency |
nord_545_0 | Overview of Guillain-Barré Syndrome | Introduction Guillain-Barré syndrome (GBS) is a rare, rapidly progressive disease due to inflammation of the nerves (polyneuritis) causing muscle weakness, sometimes progressing to complete paralysis. GBS affects about one or two people each year in every 100,000 population. Its exact cause is unknown. About half the people with the disease have a gastrointestinal or respiratory infection a few days before the onset. According to strong evidence, the infection produces an immune response which damages the nerve fibers causing weakness and loss of sensation. In milder disease the damage only affects the sheaths of the nerve fibers (like the coating round an electric wire). This blocks the transmission of nerve impulses. It can recover completely in a few weeks. In more severe disease, the immune response damages the conducting cores of the nerve fibers (that is the electric wires themselves). This takes longer to get better and may cause permanent weakness. | Overview of Guillain-Barré Syndrome. Introduction Guillain-Barré syndrome (GBS) is a rare, rapidly progressive disease due to inflammation of the nerves (polyneuritis) causing muscle weakness, sometimes progressing to complete paralysis. GBS affects about one or two people each year in every 100,000 population. Its exact cause is unknown. About half the people with the disease have a gastrointestinal or respiratory infection a few days before the onset. According to strong evidence, the infection produces an immune response which damages the nerve fibers causing weakness and loss of sensation. In milder disease the damage only affects the sheaths of the nerve fibers (like the coating round an electric wire). This blocks the transmission of nerve impulses. It can recover completely in a few weeks. In more severe disease, the immune response damages the conducting cores of the nerve fibers (that is the electric wires themselves). This takes longer to get better and may cause permanent weakness. | 545 | Guillain-Barré Syndrome |
nord_545_1 | Symptoms of Guillain-Barré Syndrome | Weakness usually begins in the legs and spreads to the arms and body. Sometimes it spreads to the breathing muscles, face and throat. In up to a quarter of people with GBS, the breathing muscles become so weak as to need temporary support of respiration on a breathing machine. Feelings of tingling, pins and needles, and numbness (loss of feeling) are common. These are due to damage to the sensory nerves that signal feeling from the skin and joints. The abnormal feelings are usually worst in the feet and hands. The tingling may be painful and the muscles may also hurt. The symptoms usually worsen for the first two weeks but the progression may last as little as one day or as long as four weeks. Symptoms usually affect both sides of the body equally.Most people only have symptoms in their arms and legs but severely affected people have more serious symptoms. They may have difficulty swallowing and become breathless. They may become unable to empty their bladder and bowel. Their pulse may go too fast or too slow and the blood pressure may rise too high or fall too low. Modern medical and nursing care can cope with all these problems as explained below.Symptoms vary widely. Some people only develop mild weakness not affecting walking and lasting only a few weeks. Others become completely paralyzed so that they cannot even move their eyes. Improvement typically starts days to several weeks after the worst has been reached and people go on improving for several months. About 20% of patients still have disability for more than a year, for instance needing aids to walk. In people left with severe weakness, slow improvement continues for two or more years. | Symptoms of Guillain-Barré Syndrome. Weakness usually begins in the legs and spreads to the arms and body. Sometimes it spreads to the breathing muscles, face and throat. In up to a quarter of people with GBS, the breathing muscles become so weak as to need temporary support of respiration on a breathing machine. Feelings of tingling, pins and needles, and numbness (loss of feeling) are common. These are due to damage to the sensory nerves that signal feeling from the skin and joints. The abnormal feelings are usually worst in the feet and hands. The tingling may be painful and the muscles may also hurt. The symptoms usually worsen for the first two weeks but the progression may last as little as one day or as long as four weeks. Symptoms usually affect both sides of the body equally.Most people only have symptoms in their arms and legs but severely affected people have more serious symptoms. They may have difficulty swallowing and become breathless. They may become unable to empty their bladder and bowel. Their pulse may go too fast or too slow and the blood pressure may rise too high or fall too low. Modern medical and nursing care can cope with all these problems as explained below.Symptoms vary widely. Some people only develop mild weakness not affecting walking and lasting only a few weeks. Others become completely paralyzed so that they cannot even move their eyes. Improvement typically starts days to several weeks after the worst has been reached and people go on improving for several months. About 20% of patients still have disability for more than a year, for instance needing aids to walk. In people left with severe weakness, slow improvement continues for two or more years. | 545 | Guillain-Barré Syndrome |
nord_545_2 | Causes of Guillain-Barré Syndrome | The cause of GBS is inflammation of the peripheral nerves. These nerves normally take messages to and from the skin and muscles to the brain and spinal cord. There is strong evidence that the cause is autoimmune. The immune system produces an immune response to an infection which cross-reacts with the nerves. It usually reacts with and damages the outer coating sheath of the nerve fibers, called myelin. In more severely affected people, this damage also affects the central conducting core of the nerve, called the axon. In some people the axon is itself the main target of the autoimmune response.There are three different forms of GBS:The different forms have similar symptoms, signs and disease courses except for the absence of sensory symptoms and signs in acute motor axonal neuropathy. They are distinguished by nerve conduction tests (see below). The treatments used and outcomes are also the same.The infections which trigger the autoimmune response include:Less, usually much less, than 1 in a 1,000 of people who catch these infections get GBS. | Causes of Guillain-Barré Syndrome. The cause of GBS is inflammation of the peripheral nerves. These nerves normally take messages to and from the skin and muscles to the brain and spinal cord. There is strong evidence that the cause is autoimmune. The immune system produces an immune response to an infection which cross-reacts with the nerves. It usually reacts with and damages the outer coating sheath of the nerve fibers, called myelin. In more severely affected people, this damage also affects the central conducting core of the nerve, called the axon. In some people the axon is itself the main target of the autoimmune response.There are three different forms of GBS:The different forms have similar symptoms, signs and disease courses except for the absence of sensory symptoms and signs in acute motor axonal neuropathy. They are distinguished by nerve conduction tests (see below). The treatments used and outcomes are also the same.The infections which trigger the autoimmune response include:Less, usually much less, than 1 in a 1,000 of people who catch these infections get GBS. | 545 | Guillain-Barré Syndrome |
nord_545_3 | Affects of Guillain-Barré Syndrome | Affects of Guillain-Barré Syndrome. | 545 | Guillain-Barré Syndrome |
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nord_545_4 | Related disorders of Guillain-Barré Syndrome | We have described the common form of GBS but some people have a similar illness but lack some characteristic features or have additional features. For instance, Miller Fisher syndrome (https://rarediseases.org/rare-diseases/miller-fisher-syndrome/), has three main features:Some people have these features as well as the usual weakness seen in GBS: their disease is called the GBS-Miller Fisher overlap syndrome. Other people have only parts of GBS or Fisher syndrome, for instance weakness of the face, throat and arms or weakness of the face and loss of tendon reflexes.Guillain-Barré syndrome always has a rapid onset reaching its worst within two or sometimes as long as four weeks. It is rare for it to occur again. Another illness, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), usually develops more slowly, reaching its worst in more than eight weeks. Many of the symptoms, such as weakness affect walking but CIDP does not usually affect the breathing muscles, throat or face. Unlike GBS, CIDP persists and progresses over many months or years or may improve and then come back again. Rarely CIDP begins rapidly, like GBS. | Related disorders of Guillain-Barré Syndrome. We have described the common form of GBS but some people have a similar illness but lack some characteristic features or have additional features. For instance, Miller Fisher syndrome (https://rarediseases.org/rare-diseases/miller-fisher-syndrome/), has three main features:Some people have these features as well as the usual weakness seen in GBS: their disease is called the GBS-Miller Fisher overlap syndrome. Other people have only parts of GBS or Fisher syndrome, for instance weakness of the face, throat and arms or weakness of the face and loss of tendon reflexes.Guillain-Barré syndrome always has a rapid onset reaching its worst within two or sometimes as long as four weeks. It is rare for it to occur again. Another illness, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), usually develops more slowly, reaching its worst in more than eight weeks. Many of the symptoms, such as weakness affect walking but CIDP does not usually affect the breathing muscles, throat or face. Unlike GBS, CIDP persists and progresses over many months or years or may improve and then come back again. Rarely CIDP begins rapidly, like GBS. | 545 | Guillain-Barré Syndrome |
nord_545_5 | Diagnosis of Guillain-Barré Syndrome | Guillain-Barré syndrome is only one of many causes of acute weakness and numbness. The diagnosis requires recognition of the characteristic symptoms and signs. Because the disease is rare, diagnosis may be difficult for the non-specialist and referral to a neurologist is usually appropriate. Clinical examination shows loss of the tendon reflexes and supports the diagnosis of peripheral nerve disease. Two tests are commonly used to support the diagnosis:Other tests exclude many other causes of neuropathy such as alcohol, poisons, drugs, vasculitis (inflammation of blood vessels), vitamin deficiency and cancer. Blood tests and X-rays or scans may also be done. | Diagnosis of Guillain-Barré Syndrome. Guillain-Barré syndrome is only one of many causes of acute weakness and numbness. The diagnosis requires recognition of the characteristic symptoms and signs. Because the disease is rare, diagnosis may be difficult for the non-specialist and referral to a neurologist is usually appropriate. Clinical examination shows loss of the tendon reflexes and supports the diagnosis of peripheral nerve disease. Two tests are commonly used to support the diagnosis:Other tests exclude many other causes of neuropathy such as alcohol, poisons, drugs, vasculitis (inflammation of blood vessels), vitamin deficiency and cancer. Blood tests and X-rays or scans may also be done. | 545 | Guillain-Barré Syndrome |
nord_545_6 | Therapies of Guillain-Barré Syndrome | The most important parts of treatment are general medical and nursing care, physiotherapy, and rehabilitation. Because of the risks of breathing failure and heart-beat instability in the acute stage, people with severe disease need to be in a ward with facilities for monitoring the pulse and breathing. If breathing becomes difficult, mechanical ventilation with a breathing machine in an intensive care unit becomes necessary. For this, a special plastic tube, called an endotracheal tube, connects the person to the breathing machine via the mouth or nose. If mechanical ventilation lasts more than a few days, it is more comfortable to put the tube in the throat by making a small opening in the windpipe for the purpose (an operation called a tracheostomy). After recovery, the tube is removed and the opening gradually closes on its own. Difficulty swallowing requires insertion of a thin plastic tube through the nose into the stomach for feeding and drinking. Medicines and nursing measures treat pain and reduce the risk of veins clotting, bed sores and constipation. Physical therapy helps muscle strength and function and prevents muscle shortening and joint stiffness. When people become medically stable, they often move to a rehabilitation center for physical and occupational therapy. Psychological support is important throughout the illness.Two treatments accelerate recovery from GBS, plasma exchange (PE, also called plasmapheresis) and intravenous immune globulin (IVIg). PE connects one vein via a thin plastic tube to a machine which separates the plasma (the liquid portion of the blood) from the red blood cells and returns the red blood cells with a plasma substitute via another vein. It removes harmful substances, especially the antibodies which cause GBS. IVIg consists of giving high doses of immune globulin (the antibodies in the blood) into a vein. The immune globulin comes from highly purified pooled plasma from thousands of healthy people. It probably works by blocking the effects of the harmful antibodies which cause GBS. IVIg is more convenient and more widely available than PE but both are equally helpful. Combining the two does not help more. Early treatment within the first two weeks after the onset of GBS symptoms is preferable. No other treatments hasten recovery. Against expectations, steroids have not been effective in clinical trials.Outlook
The majority of people recover completely or nearly completely. However, some have mild residual effects such as foot drop or abnormal feeling in the feet and hands for two years or more. Persistent fatigue and pain may be problematic. Fewer than 15 percent have substantial long-term disability severe enough to need a cane, walker or wheelchair. Death from GBS does occur but in fewer than 5 percent of patients and is rare in countries with intensive care facilities. Recurrence is rare.Most variants of GBS are treated in a similar manner with IVIg or PE. The related condition, chronic inflammatory demyelinating polyradiculoneuropathy (https://rarediseases.org/rare-diseases/chronic-inflammatory-demyelinating-polyneuropathy/), is also treated with PE and IVIg but, unlike GBS, it also responds to corticosteroids. | Therapies of Guillain-Barré Syndrome. The most important parts of treatment are general medical and nursing care, physiotherapy, and rehabilitation. Because of the risks of breathing failure and heart-beat instability in the acute stage, people with severe disease need to be in a ward with facilities for monitoring the pulse and breathing. If breathing becomes difficult, mechanical ventilation with a breathing machine in an intensive care unit becomes necessary. For this, a special plastic tube, called an endotracheal tube, connects the person to the breathing machine via the mouth or nose. If mechanical ventilation lasts more than a few days, it is more comfortable to put the tube in the throat by making a small opening in the windpipe for the purpose (an operation called a tracheostomy). After recovery, the tube is removed and the opening gradually closes on its own. Difficulty swallowing requires insertion of a thin plastic tube through the nose into the stomach for feeding and drinking. Medicines and nursing measures treat pain and reduce the risk of veins clotting, bed sores and constipation. Physical therapy helps muscle strength and function and prevents muscle shortening and joint stiffness. When people become medically stable, they often move to a rehabilitation center for physical and occupational therapy. Psychological support is important throughout the illness.Two treatments accelerate recovery from GBS, plasma exchange (PE, also called plasmapheresis) and intravenous immune globulin (IVIg). PE connects one vein via a thin plastic tube to a machine which separates the plasma (the liquid portion of the blood) from the red blood cells and returns the red blood cells with a plasma substitute via another vein. It removes harmful substances, especially the antibodies which cause GBS. IVIg consists of giving high doses of immune globulin (the antibodies in the blood) into a vein. The immune globulin comes from highly purified pooled plasma from thousands of healthy people. It probably works by blocking the effects of the harmful antibodies which cause GBS. IVIg is more convenient and more widely available than PE but both are equally helpful. Combining the two does not help more. Early treatment within the first two weeks after the onset of GBS symptoms is preferable. No other treatments hasten recovery. Against expectations, steroids have not been effective in clinical trials.Outlook
The majority of people recover completely or nearly completely. However, some have mild residual effects such as foot drop or abnormal feeling in the feet and hands for two years or more. Persistent fatigue and pain may be problematic. Fewer than 15 percent have substantial long-term disability severe enough to need a cane, walker or wheelchair. Death from GBS does occur but in fewer than 5 percent of patients and is rare in countries with intensive care facilities. Recurrence is rare.Most variants of GBS are treated in a similar manner with IVIg or PE. The related condition, chronic inflammatory demyelinating polyradiculoneuropathy (https://rarediseases.org/rare-diseases/chronic-inflammatory-demyelinating-polyneuropathy/), is also treated with PE and IVIg but, unlike GBS, it also responds to corticosteroids. | 545 | Guillain-Barré Syndrome |
nord_546_0 | Overview of Hailey-Hailey Disease | SummaryHailey-Hailey disease is a rare genetic disorder that is characterized by blisters and erosions most often affecting the neck, armpits, skin folds and genitals. The lesions may come and go and usually heal without scarring. Sunlight, heat, sweating and friction often aggravate the disorder. The symptoms of Hailey-Hailey disease occur because of the failure of skin cells to stick together resulting in the breakdown of affected skin layers. Hailey-Hailey disease occurs due to a mutation in a specific gene that creates a protein that is essential for the proper health of skin. The disorder becomes apparent after puberty, usually by the third or fourth decade, but symptoms can develop at any age.IntroductionHailey-Hailey disease is also known as familial benign pemphigus, which has created significant confusion in the medical literature. Pemphigus is a general term for a group of rare autoimmune blistering skin disorders. The symptoms and skin damage of pemphigus and Hailey-Hailey disease are similar. However, pemphigus is an autoimmune disorder, a disorder that occurs when the body’s own immune system mistakenly attacks healthy tissue. Hailey-Hailey disease is not an autoimmune disorder and there are no autoantibodies. Hailey-Hailey disease is a distinct genetic disorder caused by a gene mutation. | Overview of Hailey-Hailey Disease. SummaryHailey-Hailey disease is a rare genetic disorder that is characterized by blisters and erosions most often affecting the neck, armpits, skin folds and genitals. The lesions may come and go and usually heal without scarring. Sunlight, heat, sweating and friction often aggravate the disorder. The symptoms of Hailey-Hailey disease occur because of the failure of skin cells to stick together resulting in the breakdown of affected skin layers. Hailey-Hailey disease occurs due to a mutation in a specific gene that creates a protein that is essential for the proper health of skin. The disorder becomes apparent after puberty, usually by the third or fourth decade, but symptoms can develop at any age.IntroductionHailey-Hailey disease is also known as familial benign pemphigus, which has created significant confusion in the medical literature. Pemphigus is a general term for a group of rare autoimmune blistering skin disorders. The symptoms and skin damage of pemphigus and Hailey-Hailey disease are similar. However, pemphigus is an autoimmune disorder, a disorder that occurs when the body’s own immune system mistakenly attacks healthy tissue. Hailey-Hailey disease is not an autoimmune disorder and there are no autoantibodies. Hailey-Hailey disease is a distinct genetic disorder caused by a gene mutation. | 546 | Hailey-Hailey Disease |
nord_546_1 | Symptoms of Hailey-Hailey Disease | The symptoms and severity of Hailey-Hailey disease varies from one person to another, even among members of the same family. In most cases, there is a family history of the disorder.Hailey-Hailey usually first appears as an erosive, blistering skin rash, most often affecting the armpits, neck, chest and groin. The lesions may develop a yellow crusty overlying layer. In many cases, the rash may itch or cause a burning sensation. The lesions can separate leaving painful, cracked skin. Secondary infection of the skin lesions can also occur and may cause an unpleasant odor.The skin lesions that characterize Hailey-Hailey disease are generally relapsing and remitting, which means that they go away on their own but recur periodically. The length of an outbreak and the time between the lesions going away and a recurrence varies. When the lesions heal, they generally do not leave scars. The skin lesions are worsened by friction, heat, injury and sun exposure. | Symptoms of Hailey-Hailey Disease. The symptoms and severity of Hailey-Hailey disease varies from one person to another, even among members of the same family. In most cases, there is a family history of the disorder.Hailey-Hailey usually first appears as an erosive, blistering skin rash, most often affecting the armpits, neck, chest and groin. The lesions may develop a yellow crusty overlying layer. In many cases, the rash may itch or cause a burning sensation. The lesions can separate leaving painful, cracked skin. Secondary infection of the skin lesions can also occur and may cause an unpleasant odor.The skin lesions that characterize Hailey-Hailey disease are generally relapsing and remitting, which means that they go away on their own but recur periodically. The length of an outbreak and the time between the lesions going away and a recurrence varies. When the lesions heal, they generally do not leave scars. The skin lesions are worsened by friction, heat, injury and sun exposure. | 546 | Hailey-Hailey Disease |
nord_546_2 | Causes of Hailey-Hailey Disease | Hailey-Hailey disease is caused by a genetic change (mutation) in the ATP2C1 gene. The ATP2C1 gene contains instructions for creating (encoding) a protein that acts as a calcium and magnesium pump in the cells. This protein pumps calcium or magnesium ions into a specialized organelle in the cell known as the Golgi apparatus. Calcium ions play an essential role in cell-to-cell adhesion and, when the calcium pump does not function properly, the affected cells will not stick together, damaging the skin (acantholysis). The exact process by which loss or improper function of the protein product of the ATP2C1 gene causes Hailey-Hailey disease is not fully understood. The protein is most active in keratinocytes, the main cell type of the outermost layer of skin (epidermis). Failure of keratinocytes to stick together results in the blistering seen in the disease.Hailey-Hailey disease follows an autosomal dominant inheritance pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | Causes of Hailey-Hailey Disease. Hailey-Hailey disease is caused by a genetic change (mutation) in the ATP2C1 gene. The ATP2C1 gene contains instructions for creating (encoding) a protein that acts as a calcium and magnesium pump in the cells. This protein pumps calcium or magnesium ions into a specialized organelle in the cell known as the Golgi apparatus. Calcium ions play an essential role in cell-to-cell adhesion and, when the calcium pump does not function properly, the affected cells will not stick together, damaging the skin (acantholysis). The exact process by which loss or improper function of the protein product of the ATP2C1 gene causes Hailey-Hailey disease is not fully understood. The protein is most active in keratinocytes, the main cell type of the outermost layer of skin (epidermis). Failure of keratinocytes to stick together results in the blistering seen in the disease.Hailey-Hailey disease follows an autosomal dominant inheritance pattern. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. | 546 | Hailey-Hailey Disease |
nord_546_3 | Affects of Hailey-Hailey Disease | Hailey-Hailey disease affects males and females in equal numbers. According to one estimate, the disorder affects 1 in 50,000 people in the general population. Hailey-Hailey disease often goes misdiagnosed or undiagnosed, making it difficult to determine its true frequency in the general population.Although Hailey-Hailey disease usually becomes apparent around puberty, some cases do not develop until the third or fourth decade. Hailey-Hailey disease was first described in the medical literature in 1939. | Affects of Hailey-Hailey Disease. Hailey-Hailey disease affects males and females in equal numbers. According to one estimate, the disorder affects 1 in 50,000 people in the general population. Hailey-Hailey disease often goes misdiagnosed or undiagnosed, making it difficult to determine its true frequency in the general population.Although Hailey-Hailey disease usually becomes apparent around puberty, some cases do not develop until the third or fourth decade. Hailey-Hailey disease was first described in the medical literature in 1939. | 546 | Hailey-Hailey Disease |
nord_546_4 | Related disorders of Hailey-Hailey Disease | Symptoms of the following disorders can be similar to those of Hailey-Hailey disease. Comparisons may be useful for a differential diagnosis.Keratosis follicularis, also known as Darier’s disease, is a rare, genetic skin disorder. Affected individuals develop skin lesions that consist of thickened, rough bumps (papules) or plaques that may also be greasy or have a brown or yellow crust. These hardened, scaly lesions are progressive and may gradually grow bigger or spread. The nails and mucous membranes are also affected in many cases. Additional symptoms may be present in some cases. Individuals may have periods of time when signs improve (remission), but the lesions usually recur (relapse). The specific problems vary from one individual to another. Keratosis follicularis is inherited in an autosomal dominant pattern. (For more information on this disorder, choose “keratosis follicularis” or Darier’s disease as your search term in the Rare Disease Database.)Pemphigus is a general term for a group of rare autoimmune blistering skin disorders. Autoimmune disorders occur when the body’s own immune system mistakenly attacks healthy tissue. Two main types of pemphigus are pemphigus vulgaris and pemphigus foliaceus. Each type has subtypes. Additional disorders are sometimes classified as pemphigus including paraneoplastic pemphigus and pemphigus IgA. Some physicians consider these disorders similar, yet distinct, autoimmune blistering disorders with different clinical, immunological and microscopic tissue (histological) features. The symptoms and severity associated with the various forms of pemphigus vary. All forms of pemphigus are characterized by the development of blistering eruptions on the outer layer of the skin (epidermis). In pemphigus vulgaris, lesions also develop on the mucous membranes such as those lining the inside the mouth. Mucous membranes are the thin, moist coverings of many of the body’s internal surfaces. If left untreated, pemphigus can progress to cause life-threatening complications. The exact cause of pemphigus is unknown. (For more information on this disorder, choose “pemphigus” as your search term in the Rare Disease Database.) | Related disorders of Hailey-Hailey Disease. Symptoms of the following disorders can be similar to those of Hailey-Hailey disease. Comparisons may be useful for a differential diagnosis.Keratosis follicularis, also known as Darier’s disease, is a rare, genetic skin disorder. Affected individuals develop skin lesions that consist of thickened, rough bumps (papules) or plaques that may also be greasy or have a brown or yellow crust. These hardened, scaly lesions are progressive and may gradually grow bigger or spread. The nails and mucous membranes are also affected in many cases. Additional symptoms may be present in some cases. Individuals may have periods of time when signs improve (remission), but the lesions usually recur (relapse). The specific problems vary from one individual to another. Keratosis follicularis is inherited in an autosomal dominant pattern. (For more information on this disorder, choose “keratosis follicularis” or Darier’s disease as your search term in the Rare Disease Database.)Pemphigus is a general term for a group of rare autoimmune blistering skin disorders. Autoimmune disorders occur when the body’s own immune system mistakenly attacks healthy tissue. Two main types of pemphigus are pemphigus vulgaris and pemphigus foliaceus. Each type has subtypes. Additional disorders are sometimes classified as pemphigus including paraneoplastic pemphigus and pemphigus IgA. Some physicians consider these disorders similar, yet distinct, autoimmune blistering disorders with different clinical, immunological and microscopic tissue (histological) features. The symptoms and severity associated with the various forms of pemphigus vary. All forms of pemphigus are characterized by the development of blistering eruptions on the outer layer of the skin (epidermis). In pemphigus vulgaris, lesions also develop on the mucous membranes such as those lining the inside the mouth. Mucous membranes are the thin, moist coverings of many of the body’s internal surfaces. If left untreated, pemphigus can progress to cause life-threatening complications. The exact cause of pemphigus is unknown. (For more information on this disorder, choose “pemphigus” as your search term in the Rare Disease Database.) | 546 | Hailey-Hailey Disease |
nord_546_5 | Diagnosis of Hailey-Hailey Disease | A diagnosis of Hailey-Hailey disease is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of specialized tests including the surgical removal and microscopic examination (biopsy) of affected skin tissue. A biopsy may reveal abnormal formation of keratin tissue (keratinization) and failure of cell-to-cell adhesion (acantholysis). Blood tests in individuals with Hailey-Hailey disease will fail to detect antibodies, which rules out autoimmune disorders such as pemphigus.Molecular genetic testing for mutations in the ATP2C1 gene is available to confirm the diagnosis. | Diagnosis of Hailey-Hailey Disease. A diagnosis of Hailey-Hailey disease is made based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic findings and a variety of specialized tests including the surgical removal and microscopic examination (biopsy) of affected skin tissue. A biopsy may reveal abnormal formation of keratin tissue (keratinization) and failure of cell-to-cell adhesion (acantholysis). Blood tests in individuals with Hailey-Hailey disease will fail to detect antibodies, which rules out autoimmune disorders such as pemphigus.Molecular genetic testing for mutations in the ATP2C1 gene is available to confirm the diagnosis. | 546 | Hailey-Hailey Disease |
nord_546_6 | Therapies of Hailey-Hailey Disease | Treatment
The treatment of Hailey-Hailey disease is directed toward the specific symptoms that are apparent in each individual. Specific therapies depend upon several factors including the extent and severity of the disease and an individual’s age and general health.Individuals with Hailey-Hailey disease are encouraged to avoid “triggers” such as sunburn, sweating and friction and to keep affected areas dry. For some individuals, sunscreen, loose clothing, moisturizing creams and avoiding excessive heat may help prevent outbreaks.Cool compresses, dressings, mild corticosteroid creams and topical antibiotics may be effective in treating mild cases. More serious cases may require systemic antibiotics or stronger corticosteroid creams. Long-term corticosteroid therapy is not recommended because it can further weaken damaged skin over time.Drugs that fight bacterial, fungal or viral infections are also commonly used to treat or prevent secondary infection sometimes associated with Hailey-Hailey disease.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Hailey-Hailey Disease. Treatment
The treatment of Hailey-Hailey disease is directed toward the specific symptoms that are apparent in each individual. Specific therapies depend upon several factors including the extent and severity of the disease and an individual’s age and general health.Individuals with Hailey-Hailey disease are encouraged to avoid “triggers” such as sunburn, sweating and friction and to keep affected areas dry. For some individuals, sunscreen, loose clothing, moisturizing creams and avoiding excessive heat may help prevent outbreaks.Cool compresses, dressings, mild corticosteroid creams and topical antibiotics may be effective in treating mild cases. More serious cases may require systemic antibiotics or stronger corticosteroid creams. Long-term corticosteroid therapy is not recommended because it can further weaken damaged skin over time.Drugs that fight bacterial, fungal or viral infections are also commonly used to treat or prevent secondary infection sometimes associated with Hailey-Hailey disease.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive. | 546 | Hailey-Hailey Disease |
nord_547_0 | Overview of Haim-Munk Syndrome | Haim-Munk syndrome is a rare genetic disorder characterized by the development of red, scaly thickened patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis), frequent pus-producing (pyogenic) skin infections, overgrowth (hypertrophy) of the fingernails and toenails (onychogryposis), and degeneration of the structures that surround and support the teeth (periodontosis). Periodontosis usually results in the premature loss of teeth. Additional features associated with the disorder may include flat feet (pes planus); abnormally long, slender fingers and toes (arachnodactyly); loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis); and/or other physical findings. Haim-Munk syndrome is inherited as an autosomal recessive trait. | Overview of Haim-Munk Syndrome. Haim-Munk syndrome is a rare genetic disorder characterized by the development of red, scaly thickened patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis), frequent pus-producing (pyogenic) skin infections, overgrowth (hypertrophy) of the fingernails and toenails (onychogryposis), and degeneration of the structures that surround and support the teeth (periodontosis). Periodontosis usually results in the premature loss of teeth. Additional features associated with the disorder may include flat feet (pes planus); abnormally long, slender fingers and toes (arachnodactyly); loss of bone tissue at the ends of the fingers and/or toes (acroosteolysis); and/or other physical findings. Haim-Munk syndrome is inherited as an autosomal recessive trait. | 547 | Haim-Munk Syndrome |
nord_547_1 | Symptoms of Haim-Munk Syndrome | Haim-Munk syndrome is a rare inherited disorder characterized by the development of dry scaly patches of skin that are abnormally red and thickened on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Such patches may appear around the age of one to five years. However, in some cases, hyperkeratosis may be present at birth (congenital). These reddened patches are usually confined to the undersides of the hands and feet, but may eventually spread to the knees and elbows. In some rare cases, the upper portions of the hands and feet, the eyelids, the lips, and the cheeks may also be affected. Affected individuals also may have frequently recurring, pus-producing (pyogenic) skin infections. In individuals with Haim-Munk syndrome, the teeth usually appear to form and erupt normally. However, most affected individuals develop chronic severe inflammation and degeneration of the tissues that surround and support the teeth (gingivitis and periodontosis). The gums and the underlying ligaments and bones that support the teeth are usually involved. When the primary (deciduous) teeth erupt, the gums become red, swell, and bleed (gingivitis). The mouth may become inflamed (stomatitis), lymph nodes may swell (regional adenopathy), and abnormal “tissue pockets” may form in the gums causing susceptibility to recurring bacterial infections. By the age of five years, the deciduous teeth often may become loose and fall out. Without appropriate treatment, most of the permanent teeth may be lost in the same manner by the age of approximately 16 years. Both deciduous and permanent teeth are usually affected in the order of their eruption. In most cases, individuals with Haim-Munk syndrome exhibit overgrowth (hypertrophy) of the fingernails and toenails causing them to become abnormally thick to appear hooked and curved inward. Most affected individuals may also have flat feet (pes planus) and/or abnormally long, slender fingers and toes (arachnodactyly). In addition, some individuals with Haim-Munk syndrome also experience numbness or tingling due to a lack of normal blood flow to the fingers and/or toes when exposed to cold temperatures (Raynaud's phenomenon). Bone tissue at the ends of the fingers and/or toes (acroosteolysis) may become frail and degrade in some cases. These findings (i.e., involving the nails, hands, and feet) may be helpful in distinguishing this disorder from Papillon-Lefevre syndrome.In one reported cases, an individuals with Haim-Munk syndrome develop destructive inflammation of the joints (arthritis) of the wrists and shoulders. | Symptoms of Haim-Munk Syndrome. Haim-Munk syndrome is a rare inherited disorder characterized by the development of dry scaly patches of skin that are abnormally red and thickened on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Such patches may appear around the age of one to five years. However, in some cases, hyperkeratosis may be present at birth (congenital). These reddened patches are usually confined to the undersides of the hands and feet, but may eventually spread to the knees and elbows. In some rare cases, the upper portions of the hands and feet, the eyelids, the lips, and the cheeks may also be affected. Affected individuals also may have frequently recurring, pus-producing (pyogenic) skin infections. In individuals with Haim-Munk syndrome, the teeth usually appear to form and erupt normally. However, most affected individuals develop chronic severe inflammation and degeneration of the tissues that surround and support the teeth (gingivitis and periodontosis). The gums and the underlying ligaments and bones that support the teeth are usually involved. When the primary (deciduous) teeth erupt, the gums become red, swell, and bleed (gingivitis). The mouth may become inflamed (stomatitis), lymph nodes may swell (regional adenopathy), and abnormal “tissue pockets” may form in the gums causing susceptibility to recurring bacterial infections. By the age of five years, the deciduous teeth often may become loose and fall out. Without appropriate treatment, most of the permanent teeth may be lost in the same manner by the age of approximately 16 years. Both deciduous and permanent teeth are usually affected in the order of their eruption. In most cases, individuals with Haim-Munk syndrome exhibit overgrowth (hypertrophy) of the fingernails and toenails causing them to become abnormally thick to appear hooked and curved inward. Most affected individuals may also have flat feet (pes planus) and/or abnormally long, slender fingers and toes (arachnodactyly). In addition, some individuals with Haim-Munk syndrome also experience numbness or tingling due to a lack of normal blood flow to the fingers and/or toes when exposed to cold temperatures (Raynaud's phenomenon). Bone tissue at the ends of the fingers and/or toes (acroosteolysis) may become frail and degrade in some cases. These findings (i.e., involving the nails, hands, and feet) may be helpful in distinguishing this disorder from Papillon-Lefevre syndrome.In one reported cases, an individuals with Haim-Munk syndrome develop destructive inflammation of the joints (arthritis) of the wrists and shoulders. | 547 | Haim-Munk Syndrome |
nord_547_2 | Causes of Haim-Munk Syndrome | Haim-Munk syndrome is 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%. According to the medical literature, parents of many individuals with Haim-Munk syndrome have been closely related by blood (consanguineous). If both parents carry an altered (mutated) gene for the disorder, there is an increased risk that their children may inherit the two genes necessary for the development of the disorder.Genetic analysis of several affected families (kindreds) suggests that Haim-Munk syndrome may be due to mutations of a gene (known as cathepsin C [CTSC]) located on the long arm (q) of chromosome 11* (11q14.1-q14.3). In addition, such analysis demonstrated that, in affected individuals, a shared, common set of genes (haplotype) surrounded the gene location (locus) and appeared to be transmitted with it as a unit, suggesting that the CTSC gene mutation was inherited from a single common ancestor.Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. Therefore, chromosome 11q14.1 refers to band 14.1 on the long arm of chromosome 11.Researchers also have found that certain mutations of the CTSC gene may cause Papillon-Lefevre syndrome (allelic disorder). (An allele is one of two or more alternative forms of a gene that may occupy a particular chromosomal location.) Papillon-Lefevre syndrome is a rare syndrome characterized by certain features similar to those seen in Haim-Munk syndrome. (For further information, please see the “Related Disorders” section of this report below.) The CTSC gene regulates production (encodes for) of an enzyme (i.e., a lysosomal protease) known as cathepsin C that is expressed in various organs and tissues. It is also thought to play a role in the differentiation of certain tightly packed cells (epithelium) that form the protective outer layer of the skin, such as of the palms, soles, and knees, and bind gum tissues of the mouth (gingiva) to the tooth surface. Mutation of the CTSC gene may result in reduced levels of cathepsin C or defective cathepsin C that cannot perform its normal functions in the body. | Causes of Haim-Munk Syndrome. Haim-Munk syndrome is 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%. According to the medical literature, parents of many individuals with Haim-Munk syndrome have been closely related by blood (consanguineous). If both parents carry an altered (mutated) gene for the disorder, there is an increased risk that their children may inherit the two genes necessary for the development of the disorder.Genetic analysis of several affected families (kindreds) suggests that Haim-Munk syndrome may be due to mutations of a gene (known as cathepsin C [CTSC]) located on the long arm (q) of chromosome 11* (11q14.1-q14.3). In addition, such analysis demonstrated that, in affected individuals, a shared, common set of genes (haplotype) surrounded the gene location (locus) and appeared to be transmitted with it as a unit, suggesting that the CTSC gene mutation was inherited from a single common ancestor.Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered. Therefore, chromosome 11q14.1 refers to band 14.1 on the long arm of chromosome 11.Researchers also have found that certain mutations of the CTSC gene may cause Papillon-Lefevre syndrome (allelic disorder). (An allele is one of two or more alternative forms of a gene that may occupy a particular chromosomal location.) Papillon-Lefevre syndrome is a rare syndrome characterized by certain features similar to those seen in Haim-Munk syndrome. (For further information, please see the “Related Disorders” section of this report below.) The CTSC gene regulates production (encodes for) of an enzyme (i.e., a lysosomal protease) known as cathepsin C that is expressed in various organs and tissues. It is also thought to play a role in the differentiation of certain tightly packed cells (epithelium) that form the protective outer layer of the skin, such as of the palms, soles, and knees, and bind gum tissues of the mouth (gingiva) to the tooth surface. Mutation of the CTSC gene may result in reduced levels of cathepsin C or defective cathepsin C that cannot perform its normal functions in the body. | 547 | Haim-Munk Syndrome |
nord_547_3 | Affects of Haim-Munk Syndrome | Haim-Munk syndrome is a rare genetic disorder that affects males and females in equal numbers. The disorder is named after the investigators (Haim S, Munk J) who originally reported the disease entity in 1965 among members of an extended Jewish family (kindred) from Cochin, India. Since then, the disorder has been described in over 50 individuals in several multigenerational Jewish families in Cochin. It has sometimes been referred to as Cochin Jewish disorder. | Affects of Haim-Munk Syndrome. Haim-Munk syndrome is a rare genetic disorder that affects males and females in equal numbers. The disorder is named after the investigators (Haim S, Munk J) who originally reported the disease entity in 1965 among members of an extended Jewish family (kindred) from Cochin, India. Since then, the disorder has been described in over 50 individuals in several multigenerational Jewish families in Cochin. It has sometimes been referred to as Cochin Jewish disorder. | 547 | Haim-Munk Syndrome |
nord_547_4 | Related disorders of Haim-Munk Syndrome | Symptoms of the following disorders may be similar to those of Haim-Munk syndrome. Comparisons may be useful for a differential diagnosis: Papillon-Lefevre syndrome is a rare genetic disorder characterized by the development of dry scaly patches of skin on the palms of the hands and the soles of the feet (palmar-plantar hyperkeratosis) and severe inflammation and degeneration of the structures that surround and support the teeth (periodontium), resulting in the premature loss of teeth (periodontoclasia). Additional features may include frequent pus-producing (pyogenic) skin infections, abnormalities of the nails (nail dystrophy), and/or excessive perspiration (hyperhidrosis). Papillon-Lefevre Syndrome is inherited as an autosomal recessive trait. As noted above (see “Causes”), evidence indicates that Papillon-Lefevre Syndrome may be due to certain mutations of the same gene (i.e., the CTSC gene) responsible for Haim-Munk syndrome. (For more information on this disorder, choose “Papillon Lefevre” as your search term in the Rare Disease Database.) Schopf-Schulz-Passarge syndrome is a rare genetic disorder characterized by dry, scaly skin on the palms and the soles, fragile nails, and/or the development of cysts on the eyelids. Other findings may include the early loss of primary (deciduous) teeth, absence of some or all of the permanent teeth (hypodontia), and/or lack of body and/or scalp hair (hypotrichosis). Schopf-Schulz-Passarge syndrome is thought to be inherited as an autosomal dominant trait. Jadassohn-Lewandowsky type pachyonychia congenita is a rare genetic disorder characterized by reddening, dryness, and a scaly appearance of the skin on the palms and soles (palmoplantar hyperkeratosis) and/or overgrowth and malformation of the fingernails and toenails (onychogryposis). Additional features may include the presence of teeth at birth (neonatal dentition), loss of scalp hair, excessive sweating (hyperhidrosis) of the hands and feet, hoarseness, and/or, in some cases, respiratory distress. Mental retardation may also be present in some cases. Jadassohn-Lewandowsky type pachyonychia congenita is thought to be inherited as an autosomal dominant trait. Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Meleda” as your search term in the Rare Disease Database.)There are several additional disorders that are characterized by skin abnormalities similar to those observed in Haim-Munk syndrome. These may include psoriasis, epidermolytic hyperkeratosis, and some forms of ectodermal dysplasias. (For more information on these disorders, choose “Psoriasis,” “Epidermolytic Hyperkeratosis,” and “Ectodermal Dysplasia” as your search terms in the Rare Disease Database.) | Related disorders of Haim-Munk Syndrome. Symptoms of the following disorders may be similar to those of Haim-Munk syndrome. Comparisons may be useful for a differential diagnosis: Papillon-Lefevre syndrome is a rare genetic disorder characterized by the development of dry scaly patches of skin on the palms of the hands and the soles of the feet (palmar-plantar hyperkeratosis) and severe inflammation and degeneration of the structures that surround and support the teeth (periodontium), resulting in the premature loss of teeth (periodontoclasia). Additional features may include frequent pus-producing (pyogenic) skin infections, abnormalities of the nails (nail dystrophy), and/or excessive perspiration (hyperhidrosis). Papillon-Lefevre Syndrome is inherited as an autosomal recessive trait. As noted above (see “Causes”), evidence indicates that Papillon-Lefevre Syndrome may be due to certain mutations of the same gene (i.e., the CTSC gene) responsible for Haim-Munk syndrome. (For more information on this disorder, choose “Papillon Lefevre” as your search term in the Rare Disease Database.) Schopf-Schulz-Passarge syndrome is a rare genetic disorder characterized by dry, scaly skin on the palms and the soles, fragile nails, and/or the development of cysts on the eyelids. Other findings may include the early loss of primary (deciduous) teeth, absence of some or all of the permanent teeth (hypodontia), and/or lack of body and/or scalp hair (hypotrichosis). Schopf-Schulz-Passarge syndrome is thought to be inherited as an autosomal dominant trait. Jadassohn-Lewandowsky type pachyonychia congenita is a rare genetic disorder characterized by reddening, dryness, and a scaly appearance of the skin on the palms and soles (palmoplantar hyperkeratosis) and/or overgrowth and malformation of the fingernails and toenails (onychogryposis). Additional features may include the presence of teeth at birth (neonatal dentition), loss of scalp hair, excessive sweating (hyperhidrosis) of the hands and feet, hoarseness, and/or, in some cases, respiratory distress. Mental retardation may also be present in some cases. Jadassohn-Lewandowsky type pachyonychia congenita is thought to be inherited as an autosomal dominant trait. Meleda disease is an extremely rare inherited skin disorder characterized by the slowly progressive development of dry, thick patches of skin on the palms of the hands and soles of the feet (palmoplantar hyperkeratosis). Affected skin may be unusually red (erythema) and become abnormally thick and scaly (symmetrical cornification). Affected children may also exhibit various abnormalities of the nails; excessive sweating (hyperhidrosis) associated with an unpleasant odor; and/or, in some cases, development of small, firm raised lesions (lichenoid plaques). The range and severity of symptoms may vary from case to case. Meleda disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Meleda” as your search term in the Rare Disease Database.)There are several additional disorders that are characterized by skin abnormalities similar to those observed in Haim-Munk syndrome. These may include psoriasis, epidermolytic hyperkeratosis, and some forms of ectodermal dysplasias. (For more information on these disorders, choose “Psoriasis,” “Epidermolytic Hyperkeratosis,” and “Ectodermal Dysplasia” as your search terms in the Rare Disease Database.) | 547 | Haim-Munk Syndrome |
nord_547_5 | Diagnosis of Haim-Munk Syndrome | The diagnosis of Haim-Munk syndrome may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In some cases, skin abnormalities, including characteristic red, scaly thick patches of skin (hyperkeratosis) on the palms of the hands and the soles of the feet, may be apparent at birth (congenital) or during infancy. In most cases, Haim-Munk syndrome may not be firmly distinguished from other disorders with similar skin abnormalities until the inflammation and degeneration of the tissues surrounding and supporting the teeth (periodontium) becomes apparent. This usually occurs between the third and fifth year of life, when the infant teeth (deciduous) begin to erupt.In addition, identification of physical findings specific to Haim-Munk syndrome is necessary to distinguish this disorder from Papillon-Lefevre Syndrome. These findings may include the abnormal growth of fingernails and toenails (onychogryphosis), unusually long, slender fingers and toes (arachnodactyly), heightened sensitivity of the fingers and toes to cold temperatures, loss of bone tissue in fingers and toes (acroosteolysis), and/or flat feet (pes planus). | Diagnosis of Haim-Munk Syndrome. The diagnosis of Haim-Munk syndrome may be confirmed by a thorough clinical evaluation that includes a detailed patient history and identification of characteristic physical findings. In some cases, skin abnormalities, including characteristic red, scaly thick patches of skin (hyperkeratosis) on the palms of the hands and the soles of the feet, may be apparent at birth (congenital) or during infancy. In most cases, Haim-Munk syndrome may not be firmly distinguished from other disorders with similar skin abnormalities until the inflammation and degeneration of the tissues surrounding and supporting the teeth (periodontium) becomes apparent. This usually occurs between the third and fifth year of life, when the infant teeth (deciduous) begin to erupt.In addition, identification of physical findings specific to Haim-Munk syndrome is necessary to distinguish this disorder from Papillon-Lefevre Syndrome. These findings may include the abnormal growth of fingernails and toenails (onychogryphosis), unusually long, slender fingers and toes (arachnodactyly), heightened sensitivity of the fingers and toes to cold temperatures, loss of bone tissue in fingers and toes (acroosteolysis), and/or flat feet (pes planus). | 547 | Haim-Munk Syndrome |
nord_547_6 | Therapies of Haim-Munk Syndrome | TreatmentThe treatment of Haim-Munk syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who evaluate and treat skin problems (dermatologists), dentists, specialists in treating disorders affecting the structures supporting and surrounding the teeth (periodontists), specialists in treating disorders affecting the feet (podiatrists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Physicians may carefully monitor affected individuals to help prevent and ensure early identification of infection. If infection occurs, antibiotic therapy may be prescribed.Limited success has been found in treating associated skin abnormalities with topical lubricants. In some cases, surgery and skin grafts may be used to alleviate skin problems. Use of special footwear may help affected individuals who exhibit flat feet (pes planus). Protective clothing may alleviate the discomfort experienced during exposure to cold temperatures.Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Haim-Munk Syndrome. TreatmentThe treatment of Haim-Munk syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, physicians who evaluate and treat skin problems (dermatologists), dentists, specialists in treating disorders affecting the structures supporting and surrounding the teeth (periodontists), specialists in treating disorders affecting the feet (podiatrists), and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Physicians may carefully monitor affected individuals to help prevent and ensure early identification of infection. If infection occurs, antibiotic therapy may be prescribed.Limited success has been found in treating associated skin abnormalities with topical lubricants. In some cases, surgery and skin grafts may be used to alleviate skin problems. Use of special footwear may help affected individuals who exhibit flat feet (pes planus). Protective clothing may alleviate the discomfort experienced during exposure to cold temperatures.Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. | 547 | Haim-Munk Syndrome |
nord_548_0 | Overview of Hairy Cell Leukemia | General DiscussionHairy cell leukemia (HCL) is a rare type of blood cancer characterized by abnormal changes in white blood cells known as B lymphocytes. The bone marrow creates too many of these defective cells, known as “hairy cells” because of the thin hair-like projections found on their surface. Overproduction and accumulation of hairy cells causes a deficiency of normal blood cells (pancytopenia), including an abnormal decrease of certain white blood cells (neutrophils [neutropenia]) and certain red blood cells (platelets [thrombocytopenia]). Affected individuals usually exhibit fatigue, weakness, fever, weight loss, and/or abdominal discomfort due to an abnormally enlarged spleen (splenomegaly). In addition, affected individuals may have a slightly enlarged liver (hepatomegaly) and may be unusually susceptible to bruising and/or severe infection. The exact cause of hairy cell leukemia is not known. | Overview of Hairy Cell Leukemia. General DiscussionHairy cell leukemia (HCL) is a rare type of blood cancer characterized by abnormal changes in white blood cells known as B lymphocytes. The bone marrow creates too many of these defective cells, known as “hairy cells” because of the thin hair-like projections found on their surface. Overproduction and accumulation of hairy cells causes a deficiency of normal blood cells (pancytopenia), including an abnormal decrease of certain white blood cells (neutrophils [neutropenia]) and certain red blood cells (platelets [thrombocytopenia]). Affected individuals usually exhibit fatigue, weakness, fever, weight loss, and/or abdominal discomfort due to an abnormally enlarged spleen (splenomegaly). In addition, affected individuals may have a slightly enlarged liver (hepatomegaly) and may be unusually susceptible to bruising and/or severe infection. The exact cause of hairy cell leukemia is not known. | 548 | Hairy Cell Leukemia |
nord_548_1 | Symptoms of Hairy Cell Leukemia | Onset of hairy cell leukemia is usually gradual. Symptoms are nonspecific and may include a general feeling of ill health (malaise), fatigue, weakness, fever, night sweats, and/or weight loss. In addition, affected individuals may experience abdominal pain and a feeling of abdominal fullness due to an abnormally enlarged spleen (splenomegaly). In some cases, affected individuals may have a slightly enlarged liver (hepatomegaly) and may be unusually susceptible to bruising and/or severe, frequent infections. These infections were often the most serious complication of hairy cell leukemia, but occur rarely with advances in treatment. | Symptoms of Hairy Cell Leukemia. Onset of hairy cell leukemia is usually gradual. Symptoms are nonspecific and may include a general feeling of ill health (malaise), fatigue, weakness, fever, night sweats, and/or weight loss. In addition, affected individuals may experience abdominal pain and a feeling of abdominal fullness due to an abnormally enlarged spleen (splenomegaly). In some cases, affected individuals may have a slightly enlarged liver (hepatomegaly) and may be unusually susceptible to bruising and/or severe, frequent infections. These infections were often the most serious complication of hairy cell leukemia, but occur rarely with advances in treatment. | 548 | Hairy Cell Leukemia |
nord_548_2 | Causes of Hairy Cell Leukemia | The exact cause of hairy cell leukemia is unknown. The specific symptoms of hairy cell leukemia are due to overproduction of abnormal “hairy” cells, which results in a deficiency of the three main types of blood cells – red and white blood cells and platelets. Red blood cells deliver oxygen to the body, white blood cells help fight infections, and platelets assist in clotting to stop blood loss. | Causes of Hairy Cell Leukemia. The exact cause of hairy cell leukemia is unknown. The specific symptoms of hairy cell leukemia are due to overproduction of abnormal “hairy” cells, which results in a deficiency of the three main types of blood cells – red and white blood cells and platelets. Red blood cells deliver oxygen to the body, white blood cells help fight infections, and platelets assist in clotting to stop blood loss. | 548 | Hairy Cell Leukemia |
nord_548_3 | Affects of Hairy Cell Leukemia | Hairy cell leukemia is a rare disorder that affects males four times more often than females (M4:F1). Hairy cell leukemia affects about 6,000 persons in the United States. Approximately 600-800 new cases are diagnosed each year. Most of the affected individuals are males 50 years of age or older. However, the disorder may occur in individuals between 20 to 80 years of age. Hairy cell leukemia accounts for one to two percent of all cases of adult leukemia. It was first identified in 1958. | Affects of Hairy Cell Leukemia. Hairy cell leukemia is a rare disorder that affects males four times more often than females (M4:F1). Hairy cell leukemia affects about 6,000 persons in the United States. Approximately 600-800 new cases are diagnosed each year. Most of the affected individuals are males 50 years of age or older. However, the disorder may occur in individuals between 20 to 80 years of age. Hairy cell leukemia accounts for one to two percent of all cases of adult leukemia. It was first identified in 1958. | 548 | Hairy Cell Leukemia |
nord_548_4 | Related disorders of Hairy Cell Leukemia | Leukemia is a form of cancer affecting the bone marrow and blood. It is characterized by the uncontrolled accumulation of cancerous blood cells. Acute forms of leukemia often result in low levels of red and white blood cells and platelets (pancytopenia). (For more information, choose “leukemia” as your search term in the Rare Disease Database.) Myelofibrosis is a condition characterized by formation of fibrous tissue (fibrosis) within the bone marrow. Bone marrow is sponge-like tissue found within the bones of the body and is responsible for the production of all blood cells (i.e., red and white blood cells and platelets). Myelofibrosis may occur as a secondary characteristic to other disorders such as polycythemia vera, certain metabolic disorders, and/or chronic myeloid leukemia. In many cases, the cause of myelofibrosis is unknown (idiopathic). In idiopathic myelofibrosis, the ability of the bone marrow to produce red blood cells may be impaired. Symptoms of idiopathic myelofibrosis may include abnormally low levels of circulating red blood cells (anemia), an abnormally large spleen (splenomegaly), an abnormally large liver (hepatomegaly), weight loss, weakness and fatigue due to replacement of normal bone marrow cells, and/or episodes of severe pain in the abdomen, bones, and joints. (For more information on this disorder, choose “myelofibrosis” as your search term in the Rare Disease Database.) | Related disorders of Hairy Cell Leukemia. Leukemia is a form of cancer affecting the bone marrow and blood. It is characterized by the uncontrolled accumulation of cancerous blood cells. Acute forms of leukemia often result in low levels of red and white blood cells and platelets (pancytopenia). (For more information, choose “leukemia” as your search term in the Rare Disease Database.) Myelofibrosis is a condition characterized by formation of fibrous tissue (fibrosis) within the bone marrow. Bone marrow is sponge-like tissue found within the bones of the body and is responsible for the production of all blood cells (i.e., red and white blood cells and platelets). Myelofibrosis may occur as a secondary characteristic to other disorders such as polycythemia vera, certain metabolic disorders, and/or chronic myeloid leukemia. In many cases, the cause of myelofibrosis is unknown (idiopathic). In idiopathic myelofibrosis, the ability of the bone marrow to produce red blood cells may be impaired. Symptoms of idiopathic myelofibrosis may include abnormally low levels of circulating red blood cells (anemia), an abnormally large spleen (splenomegaly), an abnormally large liver (hepatomegaly), weight loss, weakness and fatigue due to replacement of normal bone marrow cells, and/or episodes of severe pain in the abdomen, bones, and joints. (For more information on this disorder, choose “myelofibrosis” as your search term in the Rare Disease Database.) | 548 | Hairy Cell Leukemia |
nord_548_5 | Diagnosis of Hairy Cell Leukemia | Diagnosis of Hairy Cell Leukemia. | 548 | Hairy Cell Leukemia |
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nord_548_6 | Therapies of Hairy Cell Leukemia | Until recently, treatment of hairy cell leukemia consisted of surgically removing the spleen (splenectomy). In rare cases, in which individuals do not respond to drug treatments, a splenectomy may still be performed. Chemotherapy drugs, specifically purine analogs such as cladribine and pentostatin, are now the initial treatment option for most individuals with hairy cell leukemia. Those who do not have any symptoms may not need treatment right away.The drug cladribine (Leustatin©) has been approved by the Food and Drug Administration (FDA) for treatment of HCL. This drug interferes with the development of cancer cells and has proven to be an effective drug in the treatment of hairy cell leukemia. The orphan drug pentostatin (Nipent) has been approved by the FDA for affected individuals who do not respond to initial therapy for hairy cell leukemia. According to studies, the drug produced “durable complete responses” in individuals with hairy cell leukemia. The drug is manufactured by SuperGen, Inc. In 2018, Lumoxiti (moxetumomab pasudotox-tdfk) was approved for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Lumoxiti is manufactured by AstraZeneca Pharmaceuticals.Approximately 10 percent of individuals will not respond to treatment with chemotherapy drugs. In addition, some individuals cannot take such drugs. In such cases, individuals may be treated with biological therapies such as alpha interferon. Biologic therapies attempt to use the body's immune system directly or indirectly to treat the malignancy.The orphan drug alpha interferon has been approved by the FDA for use in the treatment of hairy cell leukemia. The drug is manufactured by Hoffman-LaRoche and Schering Plough. Interferon is a hormone naturally produced by the body to fight viral infections. Treatment with alpha interferon may include daily injections for up to six months, followed by maintenance injections three times weekly. Side effects mimic flu-like symptoms, which diminish over time. | Therapies of Hairy Cell Leukemia. Until recently, treatment of hairy cell leukemia consisted of surgically removing the spleen (splenectomy). In rare cases, in which individuals do not respond to drug treatments, a splenectomy may still be performed. Chemotherapy drugs, specifically purine analogs such as cladribine and pentostatin, are now the initial treatment option for most individuals with hairy cell leukemia. Those who do not have any symptoms may not need treatment right away.The drug cladribine (Leustatin©) has been approved by the Food and Drug Administration (FDA) for treatment of HCL. This drug interferes with the development of cancer cells and has proven to be an effective drug in the treatment of hairy cell leukemia. The orphan drug pentostatin (Nipent) has been approved by the FDA for affected individuals who do not respond to initial therapy for hairy cell leukemia. According to studies, the drug produced “durable complete responses” in individuals with hairy cell leukemia. The drug is manufactured by SuperGen, Inc. In 2018, Lumoxiti (moxetumomab pasudotox-tdfk) was approved for the treatment of adult patients with relapsed or refractory hairy cell leukemia who have received at least two prior systemic therapies, including treatment with a purine nucleoside analog. Lumoxiti is manufactured by AstraZeneca Pharmaceuticals.Approximately 10 percent of individuals will not respond to treatment with chemotherapy drugs. In addition, some individuals cannot take such drugs. In such cases, individuals may be treated with biological therapies such as alpha interferon. Biologic therapies attempt to use the body's immune system directly or indirectly to treat the malignancy.The orphan drug alpha interferon has been approved by the FDA for use in the treatment of hairy cell leukemia. The drug is manufactured by Hoffman-LaRoche and Schering Plough. Interferon is a hormone naturally produced by the body to fight viral infections. Treatment with alpha interferon may include daily injections for up to six months, followed by maintenance injections three times weekly. Side effects mimic flu-like symptoms, which diminish over time. | 548 | Hairy Cell Leukemia |
nord_549_0 | Overview of Hajdu Cheney Syndrome | SummaryHajdu-Cheney syndrome is a rare genetic disorder. The specific symptoms and the severity can vary greatly from one person to another. The breakdown of bone (osteolysis), especially the outermost bones of the fingers and toes (acroosteolysis), is a major characteristic. In addition, affected individuals frequently have skull deformities, distinctive facial features, abnormally loose joints (joint laxity), a severe reduction of bone mass (osteoporosis), and short stature are also common. There are additional symptoms sometimes associated with the disorder including neurological problems, heart abnormalities that are present at birth (congenital), and abnormalities of the kidneys and urinary tract. Most affected individuals have normal mental development, but a small proportion show mild delays in development. Hajdu-Cheney syndrome is associated with a change (mutation) in the NOTCH2 gene. This condition can be inherited in an autosomal dominant manner, but many cases occur due to a new mutation that is not inherited.IntroductionFor some time, a rare disorder called serpentine fibula-polycystic kidney syndrome (SFPKS) shared similar symptoms with Hajdu-Cheney syndrome. Researchers now believe that these disorders are the same and that people with SFPKS have Hajdu-Cheney syndrome with some specific symptoms including malformed long bones of the legs and cysts in the kidneys. | Overview of Hajdu Cheney Syndrome. SummaryHajdu-Cheney syndrome is a rare genetic disorder. The specific symptoms and the severity can vary greatly from one person to another. The breakdown of bone (osteolysis), especially the outermost bones of the fingers and toes (acroosteolysis), is a major characteristic. In addition, affected individuals frequently have skull deformities, distinctive facial features, abnormally loose joints (joint laxity), a severe reduction of bone mass (osteoporosis), and short stature are also common. There are additional symptoms sometimes associated with the disorder including neurological problems, heart abnormalities that are present at birth (congenital), and abnormalities of the kidneys and urinary tract. Most affected individuals have normal mental development, but a small proportion show mild delays in development. Hajdu-Cheney syndrome is associated with a change (mutation) in the NOTCH2 gene. This condition can be inherited in an autosomal dominant manner, but many cases occur due to a new mutation that is not inherited.IntroductionFor some time, a rare disorder called serpentine fibula-polycystic kidney syndrome (SFPKS) shared similar symptoms with Hajdu-Cheney syndrome. Researchers now believe that these disorders are the same and that people with SFPKS have Hajdu-Cheney syndrome with some specific symptoms including malformed long bones of the legs and cysts in the kidneys. | 549 | Hajdu Cheney Syndrome |
nord_549_1 | Symptoms of Hajdu Cheney Syndrome | The signs and symptoms of Hajdu-Cheney syndrome can vary greatly among affected individuals. The disorder is present at birth (congenital), but in some individuals the signs and symptoms may be more apparent during adolescence and adulthood.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 cases, 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 the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.A characteristic finding is the breakdown of bone and tissue (osteolysis), particularly the outermost bones of the fingers and toes (acroosteolysis). This may be painless or can occur with inflammation, pain, swelling and abnormal sensations like burning or tingling (paresthesia). In severe instances, the fingers and toes may be shortened and appear clubbed or rounded. Generally, the fingers are affected worse than the toes.Some individuals also have a reduction of bone mass (osteoporosis), which predisposes individuals to fractures. Osteoporosis can be severe and fractures can be frequent. The bones of the spinal column, called the vertebrae, may be susceptible to compression fractures, in which the vertebrae collapse. This is extremely painful and can lead to spinal malformation. Some individuals may have abnormal sideways curvature of the spine (scoliosis) or an abnormal rounding of the spine (kyphosis) may occur. The long bones of the arms and legs can be misshapen or bowed. Because of these various skeletal problems, affected individuals may reach an adult height that is noticeably shorter than would otherwise be expected (short stature). Sometimes, these skeletal problems can become a significant impairment in daily life by late adolescent or early adulthood.Individuals have distinctive facial features. Some features are noted during infancy or childhood, while others become more pronounced as affected individuals age. These features include eyes that are slightly farther apart than normal (mild hypertelorism); an abnormally wide space in between the upper and lower eyelids; a single, thick eyebrow over the eyes (synophrys); low-set ears, a high arched roof of the mouth (palate); a cleft palate; a small jaw (micrognathia); flattening of the middle portion of the face; coarse hair; and a short neck. The range of motion of the neck may be limited.There are also abnormalities of the skull including open sutures. An infant’s skull has seven bones and several joints called sutures. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant’s “soft spots”. The seven bones of an infant’s skull usually fuse together until around age two or later. In affected adults, the occipital bone, which is located in the back of skull, may bulge outward, a condition called bathrocephaly.Dental abnormalities are common including permanent teeth that get blocked as they try to emerge from the gums (impacted) and upper and lower teeth may not meet correctly when biting (malocclusion). There may be early loss of permanent teeth. The gums of affected individuals may be infected and swollen and bleed (periodontal disease).Additional symptoms can include hearing loss, and joints that can be abnormally loose and flexible (joint hypermobility), and can be moved beyond their normal range. Various heart defects have been reported in some children. Abnormalities affecting the urinary tract can also occur. Some children experience protrusion of parts of the large intestine through an opening near the bellybutton (umbilical hernia). Some affected individuals may have flattening of the base of the skull (platybasia). This may occur because the base of the skull is pushed upward because of basilar invagination. Basilar invagination occurs when the upper bones of the spinal column are located higher than normal, blocking the hole in the base of skull through which the spinal column passes. This blocks the flow of the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). These conditions can cause excessive fluid accumulation and pressure within the brain (hydrocephalus), respiratory arrest, and sudden death.A subset of affected individuals has polycystic kidney disease, which is the formation of cysts within the kidneys. This can cause pain on both sides of the body between the last rib and hip (flank pain), blood in urine, and progressively poor function of the kidneys, which means that the kidneys will not be able to effectively remove waste products from the blood and excrete them in the urine. | Symptoms of Hajdu Cheney Syndrome. The signs and symptoms of Hajdu-Cheney syndrome can vary greatly among affected individuals. The disorder is present at birth (congenital), but in some individuals the signs and symptoms may be more apparent during adolescence and adulthood.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 cases, 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 the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.A characteristic finding is the breakdown of bone and tissue (osteolysis), particularly the outermost bones of the fingers and toes (acroosteolysis). This may be painless or can occur with inflammation, pain, swelling and abnormal sensations like burning or tingling (paresthesia). In severe instances, the fingers and toes may be shortened and appear clubbed or rounded. Generally, the fingers are affected worse than the toes.Some individuals also have a reduction of bone mass (osteoporosis), which predisposes individuals to fractures. Osteoporosis can be severe and fractures can be frequent. The bones of the spinal column, called the vertebrae, may be susceptible to compression fractures, in which the vertebrae collapse. This is extremely painful and can lead to spinal malformation. Some individuals may have abnormal sideways curvature of the spine (scoliosis) or an abnormal rounding of the spine (kyphosis) may occur. The long bones of the arms and legs can be misshapen or bowed. Because of these various skeletal problems, affected individuals may reach an adult height that is noticeably shorter than would otherwise be expected (short stature). Sometimes, these skeletal problems can become a significant impairment in daily life by late adolescent or early adulthood.Individuals have distinctive facial features. Some features are noted during infancy or childhood, while others become more pronounced as affected individuals age. These features include eyes that are slightly farther apart than normal (mild hypertelorism); an abnormally wide space in between the upper and lower eyelids; a single, thick eyebrow over the eyes (synophrys); low-set ears, a high arched roof of the mouth (palate); a cleft palate; a small jaw (micrognathia); flattening of the middle portion of the face; coarse hair; and a short neck. The range of motion of the neck may be limited.There are also abnormalities of the skull including open sutures. An infant’s skull has seven bones and several joints called sutures. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant’s “soft spots”. The seven bones of an infant’s skull usually fuse together until around age two or later. In affected adults, the occipital bone, which is located in the back of skull, may bulge outward, a condition called bathrocephaly.Dental abnormalities are common including permanent teeth that get blocked as they try to emerge from the gums (impacted) and upper and lower teeth may not meet correctly when biting (malocclusion). There may be early loss of permanent teeth. The gums of affected individuals may be infected and swollen and bleed (periodontal disease).Additional symptoms can include hearing loss, and joints that can be abnormally loose and flexible (joint hypermobility), and can be moved beyond their normal range. Various heart defects have been reported in some children. Abnormalities affecting the urinary tract can also occur. Some children experience protrusion of parts of the large intestine through an opening near the bellybutton (umbilical hernia). Some affected individuals may have flattening of the base of the skull (platybasia). This may occur because the base of the skull is pushed upward because of basilar invagination. Basilar invagination occurs when the upper bones of the spinal column are located higher than normal, blocking the hole in the base of skull through which the spinal column passes. This blocks the flow of the fluid that surrounds the brain and spinal cord (cerebrospinal fluid). These conditions can cause excessive fluid accumulation and pressure within the brain (hydrocephalus), respiratory arrest, and sudden death.A subset of affected individuals has polycystic kidney disease, which is the formation of cysts within the kidneys. This can cause pain on both sides of the body between the last rib and hip (flank pain), blood in urine, and progressively poor function of the kidneys, which means that the kidneys will not be able to effectively remove waste products from the blood and excrete them in the urine. | 549 | Hajdu Cheney Syndrome |
nord_549_2 | Causes of Hajdu Cheney Syndrome | Hajdu-Cheney syndrome is associated with a change (mutation) in the NOTCH2 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, absent, or have increased function. When there is increased function, this is called a gain-of-function mutation. In Hajdu-Cheney syndrome there is a gain of NOTCH2 protein function and increased activity of the protein. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The NOTCH2 gene produces a protein that is essential for the proper growth and development of the body. Because of the alterations to the NOTCH2 gene, the protein is stable and more effective. The exact manner that these gene changes result in the symptoms of Hajdu-Cheney syndrome is not fully understood.The changes in the NOTCH2 gene that are associated with Hajdu-Cheney syndrome are inherited in an autosomal dominant manner but many sporadic cases occur. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.In most individuals, physicians believe that the disorder occurs because of sporadic (de novo) genetic mutations that occur in the egg or sperm cell. In such situations, the disorder is not inherited from the parents and occurs randomly. | Causes of Hajdu Cheney Syndrome. Hajdu-Cheney syndrome is associated with a change (mutation) in the NOTCH2 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, absent, or have increased function. When there is increased function, this is called a gain-of-function mutation. In Hajdu-Cheney syndrome there is a gain of NOTCH2 protein function and increased activity of the protein. Depending upon the functions of the particular protein, this can affect many organ systems of the body.The NOTCH2 gene produces a protein that is essential for the proper growth and development of the body. Because of the alterations to the NOTCH2 gene, the protein is stable and more effective. The exact manner that these gene changes result in the symptoms of Hajdu-Cheney syndrome is not fully understood.The changes in the NOTCH2 gene that are associated with Hajdu-Cheney syndrome are inherited in an autosomal dominant manner but many sporadic cases occur. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.In most individuals, physicians believe that the disorder occurs because of sporadic (de novo) genetic mutations that occur in the egg or sperm cell. In such situations, the disorder is not inherited from the parents and occurs randomly. | 549 | Hajdu Cheney Syndrome |
nord_549_3 | Affects of Hajdu Cheney Syndrome | Hajdu-Cheney syndrome is an extremely rare disorder. More than 80 affected individuals have been described in the medical literature. The exact prevalence or incidence of the disorder is unknown. Rare disorders often go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. | Affects of Hajdu Cheney Syndrome. Hajdu-Cheney syndrome is an extremely rare disorder. More than 80 affected individuals have been described in the medical literature. The exact prevalence or incidence of the disorder is unknown. Rare disorders often go undiagnosed or misdiagnosed, making it difficult to determine the true frequency in the general population. | 549 | Hajdu Cheney Syndrome |
nord_549_4 | Related disorders of Hajdu Cheney Syndrome | Symptoms of the following disorders can be similar to those of Hajdu-Cheney syndrome. Comparisons may be useful for a differential diagnosis.There are numerous disorders that can have symptoms similar to those seen in Hajdu-Cheney syndrome. Acroosteolysis can be seen in various autoimmune disorders. There are other rare, genetic skeletal disorders including osteogenesis imperfecta, Melnick-Needles syndrome, Ehlers-Danlos syndrome, cleidocranial dysplasia, and certain lysosomal storage diseases. Hutchison-Gilford progeria syndrome has similar symptoms, but is distinguished by features of premature aging. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Hajdu Cheney Syndrome. Symptoms of the following disorders can be similar to those of Hajdu-Cheney syndrome. Comparisons may be useful for a differential diagnosis.There are numerous disorders that can have symptoms similar to those seen in Hajdu-Cheney syndrome. Acroosteolysis can be seen in various autoimmune disorders. There are other rare, genetic skeletal disorders including osteogenesis imperfecta, Melnick-Needles syndrome, Ehlers-Danlos syndrome, cleidocranial dysplasia, and certain lysosomal storage diseases. Hutchison-Gilford progeria syndrome has similar symptoms, but is distinguished by features of premature aging. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | 549 | Hajdu Cheney Syndrome |
nord_549_5 | Diagnosis of Hajdu Cheney Syndrome | A diagnosis of Hajdu-Cheney syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized imaging tests.Clinical Testing and Workup
Common x-rays of the skull can reveal characteristic changes including open sutures and an abnormally flattened base of the skull. X-rays of the spine can show fractures and bone loss. A test known as dual-energy X-ray absorptiometry (DXA) can be used to measure bone mineral density and detect the presence of osteoporosis.Molecular genetic testing for mutations in the NOTCH2 gene can confirm a diagnosis of Hajdu-Cheney syndrome, and is available as a diagnostic service at specialized laboratories. | Diagnosis of Hajdu Cheney Syndrome. A diagnosis of Hajdu-Cheney syndrome is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized imaging tests.Clinical Testing and Workup
Common x-rays of the skull can reveal characteristic changes including open sutures and an abnormally flattened base of the skull. X-rays of the spine can show fractures and bone loss. A test known as dual-energy X-ray absorptiometry (DXA) can be used to measure bone mineral density and detect the presence of osteoporosis.Molecular genetic testing for mutations in the NOTCH2 gene can confirm a diagnosis of Hajdu-Cheney syndrome, and is available as a diagnostic service at specialized laboratories. | 549 | Hajdu Cheney Syndrome |
nord_549_6 | Therapies of Hajdu Cheney Syndrome | Treatment
The treatment of Hajdu-Cheney syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who asses and treat disorders of the skeleton (orthopedists or orthopedic surgeons), specialists who assess and treat disorders of the heart (cardiologists), dental specialists, speech pathologists, specialists who asses and treat hearing problems (audiologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.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 Hajdu-Cheney syndrome. Some individuals have been treated with medications that prevent bone resorption in order to treat osteoporosis. Normally, bone gradually breaks down (bone resorption) and then reforms, a process called bone turnover. It appears that excessive or accelerated bone turnover contributes to Hajdu-Cheney syndrome. The benefit of these medications has not been established.Surgery may be necessary to treat various complications of Hajdu-Cheney syndrome including hydrocephalus, spinal cord abnormalities, cleft palate, and congenital heart defects. Hearing aids may be used to treat hearing loss. | Therapies of Hajdu Cheney Syndrome. Treatment
The treatment of Hajdu-Cheney syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who asses and treat disorders of the skeleton (orthopedists or orthopedic surgeons), specialists who assess and treat disorders of the heart (cardiologists), dental specialists, speech pathologists, specialists who asses and treat hearing problems (audiologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.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 Hajdu-Cheney syndrome. Some individuals have been treated with medications that prevent bone resorption in order to treat osteoporosis. Normally, bone gradually breaks down (bone resorption) and then reforms, a process called bone turnover. It appears that excessive or accelerated bone turnover contributes to Hajdu-Cheney syndrome. The benefit of these medications has not been established.Surgery may be necessary to treat various complications of Hajdu-Cheney syndrome including hydrocephalus, spinal cord abnormalities, cleft palate, and congenital heart defects. Hearing aids may be used to treat hearing loss. | 549 | Hajdu Cheney Syndrome |
nord_550_0 | Overview of Hallermann-Streiff Syndrome | SummaryHallermann-Streiff syndrome (HSS) is a rare disorder that is primarily characterized by distinctive malformations of the skull and facial (craniofacial) region; sparse hair (hypotrichosis); eye abnormalities; dental defects; degenerative skin changes (atrophy), particularly in the scalp and nasal regions; and proportionate short stature. Characteristic craniofacial features include a short, broad head (brachycephaly) with an unusually prominent forehead and/or sides of the skull (dyscephaly); a small, underdeveloped lower jaw (hypoplastic mandible); a narrow, highly arched roof of the mouth (palate); and a thin, pinched, tapering nose. Many affected individuals also have clouding of the lenses of the eyes at birth (congenital cataracts or corneal stromal opacities); unusually small eyes (microphthalmia); and/or other ocular abnormalities (glaucoma, retinal detachments). Dental defects may include natal or neonatal teeth, delayed tooth eruption, enamel hypoplasia, absent permanent teeth (hypodontia or partial adontia), abnormal tooth development resulting in short roots and early loss of teeth, and/or improper alignment of teeth. In almost all cases, HSS has appeared to occur randomly for unknown reasons (sporadically), and this syndrome is thought to be the result of a new change to genetic material (mutation).Introduction Hallermann-Streiff syndrome was first described in the medical literature in 1893. The disorder was named for two eye doctors who later independently reported cases of the syndrome, recognizing it as a distinct disease entity. | Overview of Hallermann-Streiff Syndrome. SummaryHallermann-Streiff syndrome (HSS) is a rare disorder that is primarily characterized by distinctive malformations of the skull and facial (craniofacial) region; sparse hair (hypotrichosis); eye abnormalities; dental defects; degenerative skin changes (atrophy), particularly in the scalp and nasal regions; and proportionate short stature. Characteristic craniofacial features include a short, broad head (brachycephaly) with an unusually prominent forehead and/or sides of the skull (dyscephaly); a small, underdeveloped lower jaw (hypoplastic mandible); a narrow, highly arched roof of the mouth (palate); and a thin, pinched, tapering nose. Many affected individuals also have clouding of the lenses of the eyes at birth (congenital cataracts or corneal stromal opacities); unusually small eyes (microphthalmia); and/or other ocular abnormalities (glaucoma, retinal detachments). Dental defects may include natal or neonatal teeth, delayed tooth eruption, enamel hypoplasia, absent permanent teeth (hypodontia or partial adontia), abnormal tooth development resulting in short roots and early loss of teeth, and/or improper alignment of teeth. In almost all cases, HSS has appeared to occur randomly for unknown reasons (sporadically), and this syndrome is thought to be the result of a new change to genetic material (mutation).Introduction Hallermann-Streiff syndrome was first described in the medical literature in 1893. The disorder was named for two eye doctors who later independently reported cases of the syndrome, recognizing it as a distinct disease entity. | 550 | Hallermann-Streiff Syndrome |
nord_550_1 | Symptoms of Hallermann-Streiff Syndrome | Associated symptoms and signs vary greatly in range and severity from case to case. The principal features of Hallermann-Streiff syndrome include abnormalities of the skull (cranium) and certain bones of the face (known as dyscephaly); distinctive facial features; ocular defects; dental anomalies; and/or proportionate short stature. In many cases, additional abnormalities are also present.Many affected infants have an unusually shaped skull, with abnormal shortness of the head (brachycephaly) and prominence of the forehead and/or sides of the skull (frontal and/or parietal bossing). In some cases, the head may also be relatively small (microcephaly) and the cheekbones may be underdeveloped (malar hypoplasia). In addition, there is typically abnormal widening of the fibrous joints (sutures) between certain bones of the skull and delayed closure of the two “soft spots” (fontanelles) at the front and back of the cranium.Affected individuals also often have a disproportionately small face; a high, narrow roof of the mouth (palate); and/or a small lower jaw (micrognathia) with receding chin (retrognathia). The nose is typically quite narrow and pointed; with a narrow nasal bridge, small nostrils and underdeveloped nasal cartilage that tends to become more convex (beaked) with age. The underdevelopment of the jaw and nose may result in upper airway obstruction and breathing difficulties in young children. In addition, many people with this syndrome have very sparse hair (hypotrichosis), particularly of the scalp, eyelashes, eyebrows, beard, pubic hair, and hair under the arms. Degenerative skin changes (atrophy) are also often present and largely limited to the scalp and nose. Due to such changes, the skin in these regions may appear unusually taut and thin, and regional blood vessels may seem unusually pronounced. Nasal lipofilling has been used to treat the atrophy of the nasal skin, resulting in improvement in nasal skin color and texture.The craniofacial abnormalities associated with the disorder, such as small nostrils and glossoptosis, can cause obstruction of the upper airway, particularly during the newborn period and infancy. Glossoptosis refers to downward displacement or retraction of the tongue that may occur secondary to abnormal smallness of the lower jaw (micrognathia). A narrow upper airway may lead to feeding, swallowing, and/or breathing difficulties; severe early respiratory infections; episodes in which there is absence of spontaneous breathing (apnea); anesthetic complications; and potentially life-threatening complications in severe cases. Abnormal softening of cartilage of the windpipe (tracheomalacia) has also been reported in some cases, which may further complicate swallowing and breathing difficulties. In addition, there have also been reports in which respiratory insufficiency (e.g., due to a narrow upper airway and/or tracheomalacia) has resulted in enlargement and strain of the lower right chamber (ventricle) of the heart (cor pulmonale) and possibly the left ventricle as well, leading to heart failure. Heart failure is an inability of the heart to pump enough blood to meet the body’s requirements for oxygen and other nutrients.Most individuals with HSS have ocular abnormalities. The most common ocular finding is clouding (opacity) of the lenses of both eyes at birth (congenital bilateral cataracts). According to reports in the medical literature, the cataracts, which consist of whitish, milky lens masses, may gradually spontaneously resolve (spontaneous cataract absorption) in some cases. Many individuals with this disorder also have abnormal smallness of both eyes (bilateral microphthalmia) of varying severity and/or unusually deep-set eyes (enophthalmos). As a result of these small deeply-seated eyes, patients may appear to have small, droopy eyelids (blepharoptosis). The edges of the eyelids may appear to turn inwards, particularly on the lower side (lower lid entropion) so that the eyelashes rub against the eye surface (cornea) leading to irritation, erosions and corneal opacities. Some eye experts suggest corneal stromal opacities, which are ill defined and bilateral with clear stroma between the opacities might be a hallmark feature of this condition. In some cases, additional ocular defects may also be present, such as abnormal deviation of one eye in relation to the other (strabismus); involuntary, rapid, rhythmic eye movements (nystagmus); unusual blueness of the “whites” of the eyes (blue sclera); abnormally elevated pressure of the fluid of the eyes (glaucoma); retinal detachments; down-slanting eyelids (palpebral fissures); or malformed orbital bones and/or other findings. Such ocular defects may result in varying degrees of visual impairment or, in some cases, blindness.Hallermann-Streiff syndrome is frequently characterized by dental abnormalities. These may include the eruption of teeth before or shortly after birth (natal or neonatal teeth), which may be misdiagnosed as supernumerary teeth. There is also delayed eruption of permanent teeth, abnormal tooth development, with severely undeveloped roots leading to early loss of permanent teeth and partially developed crowns, improper contact between the teeth of the upper jaw and those of the lower jaw (malocclusion), and/or persistence of the primary (deciduous) teeth. Additional dental defects may include absence of permanent teeth (hypodontia or anodontia), and/or severe, early tooth decay with enamel hypoplasia.In approximately one third of reported cases, infants with HSS are born prematurely and/or have a low birth weight. About two thirds of affected individuals have growth deficiency after birth and associated proportionate short stature.In some cases, additional physical abnormalities have also been reported in association with the disorder. Some affected males may have decreased testicular function (hypogonadism), undescended testes (cryptorchidism), and/or abnormal placement of the urinary opening of the penis (hypospadias). Skeletal abnormalities have also been reported in some cases, such as widely flared shoulder blades (winged scapula), abnormal curvature of the spine (lordosis or scoliosis), abnormal depression of the breastbone (pectus excavatum), and/or webbing of fingers and/or toes (syndactyly). Radiological findings in infants can include a large, poorly ossified skull with decreased ossification in the sutural areas, multiple Wormian bones within sutures, and severe mid-facial hypoplasia with a prominent nasal bone, small teeth, thin and gracile long bones with poor demarcation of the cortex from the medullary portion, neonatal bowing of the radius and ulna and widening at the metaphyseal ends of the long bones. Some affected infants may also have vitiligo, a condition characterized by irregular patches of skin that lack pigmentation. In addition, in rare cases, various structural heart malformations (congenital heart defects) have been reported. Such congenital heart defects have included an abnormal opening in the partition (septum) that separates the lower or upper chambers of the heart (ventricular or atrial septal defects) or abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis).In most cases, children with this disorder have normal intelligence; however, intellectual disability has been reported in approximately 15 percent of cases. In rare instances, neurologic abnormalities have been noted, including hyperactivity; seizures, and/or choreoathetosis, a condition characterized by abnormal, involuntary, irregular jerky motions and slow, writhing movements. With more patients undergoing MRI studies, various structural abnormalities of the brain have been reported. One as such case showed the absence of the corpus callosum (the thick band of nerve fibers that connects the right and left halves of the brain). | Symptoms of Hallermann-Streiff Syndrome. Associated symptoms and signs vary greatly in range and severity from case to case. The principal features of Hallermann-Streiff syndrome include abnormalities of the skull (cranium) and certain bones of the face (known as dyscephaly); distinctive facial features; ocular defects; dental anomalies; and/or proportionate short stature. In many cases, additional abnormalities are also present.Many affected infants have an unusually shaped skull, with abnormal shortness of the head (brachycephaly) and prominence of the forehead and/or sides of the skull (frontal and/or parietal bossing). In some cases, the head may also be relatively small (microcephaly) and the cheekbones may be underdeveloped (malar hypoplasia). In addition, there is typically abnormal widening of the fibrous joints (sutures) between certain bones of the skull and delayed closure of the two “soft spots” (fontanelles) at the front and back of the cranium.Affected individuals also often have a disproportionately small face; a high, narrow roof of the mouth (palate); and/or a small lower jaw (micrognathia) with receding chin (retrognathia). The nose is typically quite narrow and pointed; with a narrow nasal bridge, small nostrils and underdeveloped nasal cartilage that tends to become more convex (beaked) with age. The underdevelopment of the jaw and nose may result in upper airway obstruction and breathing difficulties in young children. In addition, many people with this syndrome have very sparse hair (hypotrichosis), particularly of the scalp, eyelashes, eyebrows, beard, pubic hair, and hair under the arms. Degenerative skin changes (atrophy) are also often present and largely limited to the scalp and nose. Due to such changes, the skin in these regions may appear unusually taut and thin, and regional blood vessels may seem unusually pronounced. Nasal lipofilling has been used to treat the atrophy of the nasal skin, resulting in improvement in nasal skin color and texture.The craniofacial abnormalities associated with the disorder, such as small nostrils and glossoptosis, can cause obstruction of the upper airway, particularly during the newborn period and infancy. Glossoptosis refers to downward displacement or retraction of the tongue that may occur secondary to abnormal smallness of the lower jaw (micrognathia). A narrow upper airway may lead to feeding, swallowing, and/or breathing difficulties; severe early respiratory infections; episodes in which there is absence of spontaneous breathing (apnea); anesthetic complications; and potentially life-threatening complications in severe cases. Abnormal softening of cartilage of the windpipe (tracheomalacia) has also been reported in some cases, which may further complicate swallowing and breathing difficulties. In addition, there have also been reports in which respiratory insufficiency (e.g., due to a narrow upper airway and/or tracheomalacia) has resulted in enlargement and strain of the lower right chamber (ventricle) of the heart (cor pulmonale) and possibly the left ventricle as well, leading to heart failure. Heart failure is an inability of the heart to pump enough blood to meet the body’s requirements for oxygen and other nutrients.Most individuals with HSS have ocular abnormalities. The most common ocular finding is clouding (opacity) of the lenses of both eyes at birth (congenital bilateral cataracts). According to reports in the medical literature, the cataracts, which consist of whitish, milky lens masses, may gradually spontaneously resolve (spontaneous cataract absorption) in some cases. Many individuals with this disorder also have abnormal smallness of both eyes (bilateral microphthalmia) of varying severity and/or unusually deep-set eyes (enophthalmos). As a result of these small deeply-seated eyes, patients may appear to have small, droopy eyelids (blepharoptosis). The edges of the eyelids may appear to turn inwards, particularly on the lower side (lower lid entropion) so that the eyelashes rub against the eye surface (cornea) leading to irritation, erosions and corneal opacities. Some eye experts suggest corneal stromal opacities, which are ill defined and bilateral with clear stroma between the opacities might be a hallmark feature of this condition. In some cases, additional ocular defects may also be present, such as abnormal deviation of one eye in relation to the other (strabismus); involuntary, rapid, rhythmic eye movements (nystagmus); unusual blueness of the “whites” of the eyes (blue sclera); abnormally elevated pressure of the fluid of the eyes (glaucoma); retinal detachments; down-slanting eyelids (palpebral fissures); or malformed orbital bones and/or other findings. Such ocular defects may result in varying degrees of visual impairment or, in some cases, blindness.Hallermann-Streiff syndrome is frequently characterized by dental abnormalities. These may include the eruption of teeth before or shortly after birth (natal or neonatal teeth), which may be misdiagnosed as supernumerary teeth. There is also delayed eruption of permanent teeth, abnormal tooth development, with severely undeveloped roots leading to early loss of permanent teeth and partially developed crowns, improper contact between the teeth of the upper jaw and those of the lower jaw (malocclusion), and/or persistence of the primary (deciduous) teeth. Additional dental defects may include absence of permanent teeth (hypodontia or anodontia), and/or severe, early tooth decay with enamel hypoplasia.In approximately one third of reported cases, infants with HSS are born prematurely and/or have a low birth weight. About two thirds of affected individuals have growth deficiency after birth and associated proportionate short stature.In some cases, additional physical abnormalities have also been reported in association with the disorder. Some affected males may have decreased testicular function (hypogonadism), undescended testes (cryptorchidism), and/or abnormal placement of the urinary opening of the penis (hypospadias). Skeletal abnormalities have also been reported in some cases, such as widely flared shoulder blades (winged scapula), abnormal curvature of the spine (lordosis or scoliosis), abnormal depression of the breastbone (pectus excavatum), and/or webbing of fingers and/or toes (syndactyly). Radiological findings in infants can include a large, poorly ossified skull with decreased ossification in the sutural areas, multiple Wormian bones within sutures, and severe mid-facial hypoplasia with a prominent nasal bone, small teeth, thin and gracile long bones with poor demarcation of the cortex from the medullary portion, neonatal bowing of the radius and ulna and widening at the metaphyseal ends of the long bones. Some affected infants may also have vitiligo, a condition characterized by irregular patches of skin that lack pigmentation. In addition, in rare cases, various structural heart malformations (congenital heart defects) have been reported. Such congenital heart defects have included an abnormal opening in the partition (septum) that separates the lower or upper chambers of the heart (ventricular or atrial septal defects) or abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis).In most cases, children with this disorder have normal intelligence; however, intellectual disability has been reported in approximately 15 percent of cases. In rare instances, neurologic abnormalities have been noted, including hyperactivity; seizures, and/or choreoathetosis, a condition characterized by abnormal, involuntary, irregular jerky motions and slow, writhing movements. With more patients undergoing MRI studies, various structural abnormalities of the brain have been reported. One as such case showed the absence of the corpus callosum (the thick band of nerve fibers that connects the right and left halves of the brain). | 550 | Hallermann-Streiff Syndrome |
nord_550_2 | Causes of Hallermann-Streiff Syndrome | In almost all reported cases, Hallermann-Streiff syndrome has occurred randomly for unknown reasons (sporadically), most likely due to a new spontaneous dominant genetic change (mutation). There have been reports of patients with this disorder reproducing successfully and bearing multiple normal children. From families with an affected child, there is little evidence for this being a recessively inherited disorder in which both parents are carriers (normal looking but carry the mutation). Therefore, the mode of inheritance of this disorder remains elusive making it difficult to determine the exact recurrent risk.Hallermann-Streiff syndrome bears some similarity to some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (caused by de novo point mutations in the LMNA gene) and mandibuloacral dysplasia (recessive disorders resulting from mutations in LMNA and ZMPSTE24). ZMPSTE24 and ICMT encode proteins involved in posttranslational processing of lamin A. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in 8 patients with Hallermann-Streiff syndrome revealed no evidence that this disorder is a type of laminopathy, but these other conditions remain part of the differential diagnosis, particularly when autosomal recessive inheritance is suspected. | Causes of Hallermann-Streiff Syndrome. In almost all reported cases, Hallermann-Streiff syndrome has occurred randomly for unknown reasons (sporadically), most likely due to a new spontaneous dominant genetic change (mutation). There have been reports of patients with this disorder reproducing successfully and bearing multiple normal children. From families with an affected child, there is little evidence for this being a recessively inherited disorder in which both parents are carriers (normal looking but carry the mutation). Therefore, the mode of inheritance of this disorder remains elusive making it difficult to determine the exact recurrent risk.Hallermann-Streiff syndrome bears some similarity to some progeroid syndromes that belong to the laminopathies, such as Hutchinson-Gilford progeria syndrome (caused by de novo point mutations in the LMNA gene) and mandibuloacral dysplasia (recessive disorders resulting from mutations in LMNA and ZMPSTE24). ZMPSTE24 and ICMT encode proteins involved in posttranslational processing of lamin A. Sequencing of the genes LMNA, ZMPSTE24 and ICMT in 8 patients with Hallermann-Streiff syndrome revealed no evidence that this disorder is a type of laminopathy, but these other conditions remain part of the differential diagnosis, particularly when autosomal recessive inheritance is suspected. | 550 | Hallermann-Streiff Syndrome |
nord_550_3 | Affects of Hallermann-Streiff Syndrome | Hallermann-Streiff syndrome appears to affect males and females in relatively equal numbers. More than 150 cases have been reported in the medical literature. | Affects of Hallermann-Streiff Syndrome. Hallermann-Streiff syndrome appears to affect males and females in relatively equal numbers. More than 150 cases have been reported in the medical literature. | 550 | Hallermann-Streiff Syndrome |
nord_550_4 | Related disorders of Hallermann-Streiff Syndrome | Symptoms of the following disorders can be similar to those of Hallermann-Streiff syndrome. Comparisons may be useful for a differential diagnosis:Hutchinson-Gilford progeria syndrome is a very rare progressive disorder of childhood characterized by premature aging (progeria); growth delays occurring in the first year of life resulting in short stature and low weight; deterioration of the layer of fatty tissue beneath the skin (subcutaneous lipodystrophy); and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated non-healing fractures, a progressive aged appearance, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. In most cases, affected individuals develop premature, widespread thickening and loss of elasticity of arterial walls (arteriosclerosis), potentially resulting in life-threatening complications. Hutchinson-Gilford progeria syndrome is due to a de novo heterozygous mutation in the lamin A gene (LMNA) on chromosome 1q22. (For more information on this disorder, choose “Hutchinson Gilford” as your search term in the Rare Disease Database) Other disorders with less severe, but overlapping features include mandibuloacral dysplasia, an autosomal recessive disorder, which is caused by different mutations in the LMNA gene or the ZMPSTE24 gene, and Werner syndrome, an autosomal recessive progeroid syndrome caused by autosomal recessive mutations in the RECQL2 gene.Wiedemann-Rautenstrauch syndrome (also known as neonatal progeroid syndrome) is an extremely rare genetic disorder characterized by an aged appearance at birth (neonatal progeroid appearance); growth delays before and after birth (prenatal and postnatal growth deficiency); and deficient or absent fatty tissue under the skin (subcutaneous lipoatrophy), causing the skin to appear abnormally thin, fragile, and wrinkled. In addition abnormal deposits of fat may accumulate around the buttocks, flanks, genitals and anus (anogenital area). Affected infants and children have distinctive facial features with unusual prominence of the forehead (frontal bossing) and the sides of the skull (parietal bossing), causing the head to appear large (pseudohydrocephalus); unusually small, underdeveloped (hypoplastic) bones of the face and abnormally small facial features; a small “beak-shaped” nose that becomes more pronounced with advancing age; and/or sparse scalp hair, eyebrows, and/or eyelashes. Most infants and children with Wiedemann-Rautenstrauch syndrome have unusually thin arms and legs; abnormally large hands and feet; progressive neurological and neuromuscular abnormalities; varying degrees of intellectual disability; and severe delays in the acquisition of skills requiring the coordination of mental and muscular activities (psychomotor retardation). In addition, affected infants and children are prone to repeated respiratory infections that may result in life-threatening complications. Wiedemann-Rautenstrauch syndrome is inherited as an autosomal recessive genetic trait. Core manifestations of this syndrome include marked pre-natal and severe post-natal growth retardation, an unusual face (triangular shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth; hypodontia), generalized lipodystrophy with localized fat masses, and-in some cases-progressive ataxia and tremor. It has been suggested that the syndrome might be caused by biallelic variants in POLR3A, identified by exome sequencing in a single patient only. There are major differences but there are also similarities in phenotype, which sustain the suggestion that the syndrome can be caused by disturbed POLR3A functioning. (For more information on this disorder, choose “Wiedemann Rautenstrauch” as your search term in the Rare Disease Database.)Seckel syndrome is an extremely rare autosomal recessive disorder characterized by growth deficiency prior to birth (intrauterine growth retardation) resulting in low birth weight. Growth deficiency continues after birth, resulting in severe proportionate short stature. Other symptoms and physical features associated with Seckel syndrome include an abnormally small head (microcephaly); varying degrees of intellectual disability; and/or unusual characteristic facial features including “beak-like” protrusion of the nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears, and/or an unusually small jaw (micrognathia). In addition, some affected infants exhibit incurving of the fifth fingers in a bent position (clinodactyly), congenital hip dysplasia, dislocated forearms (radial dislocation), and/or other physical abnormalities. Seckel syndrome inherited as an autosomal recessive genetic trait due to homozygous or compound heterozygous mutation in the ATR gene on chromosome 3q22.1-q24. Other syndromes resembling this disorder are caused by mutations in the RBBP8 gene on chromosome 18q11.31-q11.2; mutations in the CENPJ gene on chromosome 13q12; mutations in the CEP152 gene on chromosome 15q21; or mutations in CDK5RAP2 on chromosome 9q33.2. (For more information on this disorder, choose “Seckel” as your search term in the Rare Disease Database.)Osteodysplastic bird-headed dwarfism, also known as Majewski osteodysplastic primordial dwarfism (MOPD) is an extremely rare inherited disorder characterized by low birth weight, prenatal-onset growth deficiency resulting in severe proportionate short stature with an unusually small head (microcephaly), and characteristic facial features including prominence of the nose, abnormally large eyes, an unusually small jaw (micrognathia) that is recessed (retrognathia), a narrow face, and/or low-set ears. In some cases, affected children may exhibit other abnormalities, such as mild intellectual disability, skeletal deformities, and/or patchy areas of hair loss (alopecia) on the scalp. There are three types of MOPD, designated type I, II, and III that are distinguished by differences in their symptoms. All are inherited as autosomal recessive genetic traits caused by mutations in different genes (MOPD I – RNU4ATAC; MOPD II – PCNT; MOPD III – possibly the same entity as MOPD I).Among children who present with microcephaly and bilateral congenital cataracts with small eyes, one should also consider MICRO syndrome, a rare autosomal recessive disorder characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism. This disorder is caused by mutation in the RAB3GAP2 gene on chromosome 1q41; the RAB3GAP1 gene on 2q21.3; the RAB18 gene on 10p12.1; or the TBC1D20 gene on 20p13.Another possibility is early onset Cockayne syndrome, an autosomal recessive disorder resulting in severe failure to thrive, severe mental retardation, congenital cataracts, loss of adipose tissue, joint contractures, distinctive face with small, deep-set eyes and prominent nasal bridge, kyphosis, and cachectic dwarfism. This disorder is termed Cockayne syndrome type B (CSB) and caused by mutation in the gene encoding the group 6 excision-repair cross-complementing protein (ERCC6) on chromosome 10q11.23. Cockayne syndrome type A (CSA) is caused by mutation in the ERCC8 gene on chromosome 5q11. Among patients with Cockayne syndrome, approximately 80% have mutations in the ERCC6 gene. | Related disorders of Hallermann-Streiff Syndrome. Symptoms of the following disorders can be similar to those of Hallermann-Streiff syndrome. Comparisons may be useful for a differential diagnosis:Hutchinson-Gilford progeria syndrome is a very rare progressive disorder of childhood characterized by premature aging (progeria); growth delays occurring in the first year of life resulting in short stature and low weight; deterioration of the layer of fatty tissue beneath the skin (subcutaneous lipodystrophy); and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated non-healing fractures, a progressive aged appearance, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. In most cases, affected individuals develop premature, widespread thickening and loss of elasticity of arterial walls (arteriosclerosis), potentially resulting in life-threatening complications. Hutchinson-Gilford progeria syndrome is due to a de novo heterozygous mutation in the lamin A gene (LMNA) on chromosome 1q22. (For more information on this disorder, choose “Hutchinson Gilford” as your search term in the Rare Disease Database) Other disorders with less severe, but overlapping features include mandibuloacral dysplasia, an autosomal recessive disorder, which is caused by different mutations in the LMNA gene or the ZMPSTE24 gene, and Werner syndrome, an autosomal recessive progeroid syndrome caused by autosomal recessive mutations in the RECQL2 gene.Wiedemann-Rautenstrauch syndrome (also known as neonatal progeroid syndrome) is an extremely rare genetic disorder characterized by an aged appearance at birth (neonatal progeroid appearance); growth delays before and after birth (prenatal and postnatal growth deficiency); and deficient or absent fatty tissue under the skin (subcutaneous lipoatrophy), causing the skin to appear abnormally thin, fragile, and wrinkled. In addition abnormal deposits of fat may accumulate around the buttocks, flanks, genitals and anus (anogenital area). Affected infants and children have distinctive facial features with unusual prominence of the forehead (frontal bossing) and the sides of the skull (parietal bossing), causing the head to appear large (pseudohydrocephalus); unusually small, underdeveloped (hypoplastic) bones of the face and abnormally small facial features; a small “beak-shaped” nose that becomes more pronounced with advancing age; and/or sparse scalp hair, eyebrows, and/or eyelashes. Most infants and children with Wiedemann-Rautenstrauch syndrome have unusually thin arms and legs; abnormally large hands and feet; progressive neurological and neuromuscular abnormalities; varying degrees of intellectual disability; and severe delays in the acquisition of skills requiring the coordination of mental and muscular activities (psychomotor retardation). In addition, affected infants and children are prone to repeated respiratory infections that may result in life-threatening complications. Wiedemann-Rautenstrauch syndrome is inherited as an autosomal recessive genetic trait. Core manifestations of this syndrome include marked pre-natal and severe post-natal growth retardation, an unusual face (triangular shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth; hypodontia), generalized lipodystrophy with localized fat masses, and-in some cases-progressive ataxia and tremor. It has been suggested that the syndrome might be caused by biallelic variants in POLR3A, identified by exome sequencing in a single patient only. There are major differences but there are also similarities in phenotype, which sustain the suggestion that the syndrome can be caused by disturbed POLR3A functioning. (For more information on this disorder, choose “Wiedemann Rautenstrauch” as your search term in the Rare Disease Database.)Seckel syndrome is an extremely rare autosomal recessive disorder characterized by growth deficiency prior to birth (intrauterine growth retardation) resulting in low birth weight. Growth deficiency continues after birth, resulting in severe proportionate short stature. Other symptoms and physical features associated with Seckel syndrome include an abnormally small head (microcephaly); varying degrees of intellectual disability; and/or unusual characteristic facial features including “beak-like” protrusion of the nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears, and/or an unusually small jaw (micrognathia). In addition, some affected infants exhibit incurving of the fifth fingers in a bent position (clinodactyly), congenital hip dysplasia, dislocated forearms (radial dislocation), and/or other physical abnormalities. Seckel syndrome inherited as an autosomal recessive genetic trait due to homozygous or compound heterozygous mutation in the ATR gene on chromosome 3q22.1-q24. Other syndromes resembling this disorder are caused by mutations in the RBBP8 gene on chromosome 18q11.31-q11.2; mutations in the CENPJ gene on chromosome 13q12; mutations in the CEP152 gene on chromosome 15q21; or mutations in CDK5RAP2 on chromosome 9q33.2. (For more information on this disorder, choose “Seckel” as your search term in the Rare Disease Database.)Osteodysplastic bird-headed dwarfism, also known as Majewski osteodysplastic primordial dwarfism (MOPD) is an extremely rare inherited disorder characterized by low birth weight, prenatal-onset growth deficiency resulting in severe proportionate short stature with an unusually small head (microcephaly), and characteristic facial features including prominence of the nose, abnormally large eyes, an unusually small jaw (micrognathia) that is recessed (retrognathia), a narrow face, and/or low-set ears. In some cases, affected children may exhibit other abnormalities, such as mild intellectual disability, skeletal deformities, and/or patchy areas of hair loss (alopecia) on the scalp. There are three types of MOPD, designated type I, II, and III that are distinguished by differences in their symptoms. All are inherited as autosomal recessive genetic traits caused by mutations in different genes (MOPD I – RNU4ATAC; MOPD II – PCNT; MOPD III – possibly the same entity as MOPD I).Among children who present with microcephaly and bilateral congenital cataracts with small eyes, one should also consider MICRO syndrome, a rare autosomal recessive disorder characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism. This disorder is caused by mutation in the RAB3GAP2 gene on chromosome 1q41; the RAB3GAP1 gene on 2q21.3; the RAB18 gene on 10p12.1; or the TBC1D20 gene on 20p13.Another possibility is early onset Cockayne syndrome, an autosomal recessive disorder resulting in severe failure to thrive, severe mental retardation, congenital cataracts, loss of adipose tissue, joint contractures, distinctive face with small, deep-set eyes and prominent nasal bridge, kyphosis, and cachectic dwarfism. This disorder is termed Cockayne syndrome type B (CSB) and caused by mutation in the gene encoding the group 6 excision-repair cross-complementing protein (ERCC6) on chromosome 10q11.23. Cockayne syndrome type A (CSA) is caused by mutation in the ERCC8 gene on chromosome 5q11. Among patients with Cockayne syndrome, approximately 80% have mutations in the ERCC6 gene. | 550 | Hallermann-Streiff Syndrome |
nord_550_5 | Diagnosis of Hallermann-Streiff Syndrome | Hallermann-Streiff syndrome may be suspected shortly after birth or during the first year of life by the identification of characteristic physical findings and symptoms. The diagnosis may be confirmed by thorough clinical evaluation; a detailed patient history; and specialized tests (e.g., radiographic, ophthalmologic, and dental studies) that may help to detect and characterize the abnormalities associated with this disorder. Congenital cataracts with unusually small eyes (microphthalmia) are important findings for the initial diagnosis of Hallermann-Streiff syndrome, but other disorders must be considered as part of the differential diagnosis, and this is best accomplished through whole exome sequencing given the extensive differential diagnosis, which includes a number of autosomal recessive disorders. | Diagnosis of Hallermann-Streiff Syndrome. Hallermann-Streiff syndrome may be suspected shortly after birth or during the first year of life by the identification of characteristic physical findings and symptoms. The diagnosis may be confirmed by thorough clinical evaluation; a detailed patient history; and specialized tests (e.g., radiographic, ophthalmologic, and dental studies) that may help to detect and characterize the abnormalities associated with this disorder. Congenital cataracts with unusually small eyes (microphthalmia) are important findings for the initial diagnosis of Hallermann-Streiff syndrome, but other disorders must be considered as part of the differential diagnosis, and this is best accomplished through whole exome sequencing given the extensive differential diagnosis, which includes a number of autosomal recessive disorders. | 550 | Hallermann-Streiff Syndrome |
nord_550_6 | Therapies of Hallermann-Streiff Syndrome | Treatment
The treatment of Hallermann-Streiff syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians, craniofacial surgeons, eye specialists (ophthalmologists), dental specialists, and/or other health care professionals.For infants with feeding and respiratory difficulties, early disease management should include monitoring of breathing, consideration of tracheostomy (creation of an opening through the neck into the windpipe into which a tube is inserted, to help maintain an effective airway), and various supportive measures to improve feeding and ensure sufficient intake of nutrients. In addition, early surgical removal of cataracts may be recommended to help preserve vision; however, some investigators indicate that the frequency of spontaneous cataract absorption (see “Symptoms”) may be underestimated in those with Hallermann-Streiff syndrome, suggesting that it may occur in up to 50 percent of untreated patients followed up through age 5 years. These physicians may advise waiting for possible spontaneous cataract absorption in selected cases, particularly for patients with significant microphthalmia. Regular close ophthalmology follow-up is strongly recommended to identify and treat other eye abnormalities like nystagmus, ptosis and entropion, which may require surgical intervention to avoid developing a lazy eye (amblyopia) and allow appropriate development of vision. Further investigation is needed regarding the frequency of spontaneous cataract absorption and optimal treatment approaches.With respect to dental anomalies, it is important to note that the natal/neonatal teeth (teeth present at birth) may be incorrectly diagnosed as supernumerary (extra) teeth and there may be a tendency to extract them. However, apart from their role in mastication (chewing), teeth are also important for maintaining the vertical dimensions of the oral cavity, and the loss of teeth may worsen the glossoptosis (posterior location of the tongue) by over closure of the already small lower jaw (micrognathia). Whenever possible every effort should be made to preserve these prematurely erupted deciduous (baby) teeth to facilitate future nutritional intake and prevent unfavorable sequelae, until the existence of successional permanent teeth can be confirmed. Also, because individuals with Hallermann-Streiff syndrome have malformed teeth with abnormal roots and enamel hypoplasia, they are predisposed to developing severe dental caries making it imperative to ensure good dental hygiene. It may be difficult to perform root canal treatment and other therapies to preserve a tooth with underdeveloped roots, and therefore these patients need appropriate, frequent pediatric dental evaluations.Recommended disease management may also include surgical reconstruction of certain craniofacial malformations (particularly the mandibular and nasal region) at the appropriate age. Some affected individuals may have a risk of anesthetic complications, since endotracheal intubation and laryngoscopy may be difficult due to upper airway obstruction. Intubation may be required for the delivery of oxygen or anesthetic gases during surgery. A viewing tube (laryngoscope) is used before intubation to help identify the vocal cords. A breathing (endotracheal) tube is then passed through the mouth down the throat and into the windpipe. The greatest anesthetic challenge lies in the maintenance of an appropriate airway due to upper airway deformities which make mask ventilation, laryngeal exposure and tracheal intubation
difficult. The options available to circumvent the problems during difficult intubation are, awake intubation, intubation over a fiberoptic bronchoscope and intubation under inhalational anesthesia. This potential anesthetic risk must be taken into consideration by surgeons, pediatric anesthesiologists, and other health care providers when making decisions concerning surgery.For some affected infants and children with heart defects, medical treatment, surgical intervention, and/or other surgical measures may also be recommended. The specific surgical procedures performed will depend upon the size, nature, severity, and/or combination of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention is important to ensure that children with Hallermann-Streiff syndrome reach their potential. Special services that may be beneficial include special remedial education, special social support, physical therapy, and other medical, social, and/or vocational services.Genetic counseling may also be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. | Therapies of Hallermann-Streiff Syndrome. Treatment
The treatment of Hallermann-Streiff syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians, craniofacial surgeons, eye specialists (ophthalmologists), dental specialists, and/or other health care professionals.For infants with feeding and respiratory difficulties, early disease management should include monitoring of breathing, consideration of tracheostomy (creation of an opening through the neck into the windpipe into which a tube is inserted, to help maintain an effective airway), and various supportive measures to improve feeding and ensure sufficient intake of nutrients. In addition, early surgical removal of cataracts may be recommended to help preserve vision; however, some investigators indicate that the frequency of spontaneous cataract absorption (see “Symptoms”) may be underestimated in those with Hallermann-Streiff syndrome, suggesting that it may occur in up to 50 percent of untreated patients followed up through age 5 years. These physicians may advise waiting for possible spontaneous cataract absorption in selected cases, particularly for patients with significant microphthalmia. Regular close ophthalmology follow-up is strongly recommended to identify and treat other eye abnormalities like nystagmus, ptosis and entropion, which may require surgical intervention to avoid developing a lazy eye (amblyopia) and allow appropriate development of vision. Further investigation is needed regarding the frequency of spontaneous cataract absorption and optimal treatment approaches.With respect to dental anomalies, it is important to note that the natal/neonatal teeth (teeth present at birth) may be incorrectly diagnosed as supernumerary (extra) teeth and there may be a tendency to extract them. However, apart from their role in mastication (chewing), teeth are also important for maintaining the vertical dimensions of the oral cavity, and the loss of teeth may worsen the glossoptosis (posterior location of the tongue) by over closure of the already small lower jaw (micrognathia). Whenever possible every effort should be made to preserve these prematurely erupted deciduous (baby) teeth to facilitate future nutritional intake and prevent unfavorable sequelae, until the existence of successional permanent teeth can be confirmed. Also, because individuals with Hallermann-Streiff syndrome have malformed teeth with abnormal roots and enamel hypoplasia, they are predisposed to developing severe dental caries making it imperative to ensure good dental hygiene. It may be difficult to perform root canal treatment and other therapies to preserve a tooth with underdeveloped roots, and therefore these patients need appropriate, frequent pediatric dental evaluations.Recommended disease management may also include surgical reconstruction of certain craniofacial malformations (particularly the mandibular and nasal region) at the appropriate age. Some affected individuals may have a risk of anesthetic complications, since endotracheal intubation and laryngoscopy may be difficult due to upper airway obstruction. Intubation may be required for the delivery of oxygen or anesthetic gases during surgery. A viewing tube (laryngoscope) is used before intubation to help identify the vocal cords. A breathing (endotracheal) tube is then passed through the mouth down the throat and into the windpipe. The greatest anesthetic challenge lies in the maintenance of an appropriate airway due to upper airway deformities which make mask ventilation, laryngeal exposure and tracheal intubation
difficult. The options available to circumvent the problems during difficult intubation are, awake intubation, intubation over a fiberoptic bronchoscope and intubation under inhalational anesthesia. This potential anesthetic risk must be taken into consideration by surgeons, pediatric anesthesiologists, and other health care providers when making decisions concerning surgery.For some affected infants and children with heart defects, medical treatment, surgical intervention, and/or other surgical measures may also be recommended. The specific surgical procedures performed will depend upon the size, nature, severity, and/or combination of the anatomical abnormalities, their associated symptoms, and other factors.Early intervention is important to ensure that children with Hallermann-Streiff syndrome reach their potential. Special services that may be beneficial include special remedial education, special social support, physical therapy, and other medical, social, and/or vocational services.Genetic counseling may also be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. | 550 | Hallermann-Streiff Syndrome |
nord_551_0 | Overview of Hanhart Syndrome | SummaryHanhart syndrome is a rare condition characterized by a short, incompletely developed tongue (hypoglossia); absent or partially missing fingers and/or toes (hypodactylia); malformed arms and/or legs (peromelia); and an extremely small jaw (micrognathia).The severity of these physical abnormalities varies greatly from person to person. Children with this disorder often have some, but not all, of these symptoms. The cause of Hanhart syndrome is not fully understood.IntroductionHanhart syndrome is in the group of conditions known as oromandibular-limb hypogenesis syndromes (OLHS). These syndromes are characterized by underdevelopment of the limbs, mouth and jaw.Hanhart syndrome was first described in 1932. In 1950, Dr. Hanhart described three children who had a missing tongue with associated limb defects and the name ‘Hanhart syndrome’ was adopted. | Overview of Hanhart Syndrome. SummaryHanhart syndrome is a rare condition characterized by a short, incompletely developed tongue (hypoglossia); absent or partially missing fingers and/or toes (hypodactylia); malformed arms and/or legs (peromelia); and an extremely small jaw (micrognathia).The severity of these physical abnormalities varies greatly from person to person. Children with this disorder often have some, but not all, of these symptoms. The cause of Hanhart syndrome is not fully understood.IntroductionHanhart syndrome is in the group of conditions known as oromandibular-limb hypogenesis syndromes (OLHS). These syndromes are characterized by underdevelopment of the limbs, mouth and jaw.Hanhart syndrome was first described in 1932. In 1950, Dr. Hanhart described three children who had a missing tongue with associated limb defects and the name ‘Hanhart syndrome’ was adopted. | 551 | Hanhart Syndrome |
nord_551_1 | Symptoms of Hanhart Syndrome | The craniofacial abnormalities in children with Hanhart syndrome can include a small mouth (microstomia); small jaw and deeply receding jaw (micrognathia); shorty, incompletely developed tongue (hypoglossia); cleft palate; cleft tongue; broad nose; increased distance between the inner corners of the eyelids (telecanthus); lower eyelid defects; facial asymmetry; and partial absence of the jaw (mandibular hypodontia).Affected children may have fingers and/or toes that are partially missing or completely absent (ectrodactylia). In addition, lower (distal) portions of the arms and/or legs may be malformed, partially missing, and/or completely absent (amelia). Limb malformations may vary in severity from limb to limb (asymmetric).Infants with Hanhart syndrome may have loss of some motor function (paralysis) in the facial area at birth due to impairment of one or more of the 12 nerve pairs that arise from the brain (cranial nerve palsy). In many cases, congenital nerve palsy of the 6th (abducens) and/or 7th (facialis) cranial nerves is present. In rarer cases, the 3rd (oculomotorius), 5th (trigeminus), 9th (glossopharyngeus), and/or 12th (hypoglossus) cranial nerves are affected. The presence of some of these nerve palsies can worsen any feeding problems that occur because of tongue, mouth, and/or jaw abnormalities.Additional abnormalities may occur in association with Hanhart syndrome. In some affected individuals, the spleen and the gonads (i.e., testes in males, ovaries in females) may have fused together during fetal development (splenogonadal fusion). This may be manifested in males as a testicular mass or as a testis that has failed to descend into the scrotum (cryptorchidism). Some individuals may have vertical skin folds that cover the inner corners of the eyes (epicanthus); a malformation of the foot (clubfoot or talipes); an absent kidney (unilateral renal agenesis); a cyst in the brain (porencephalic cyst); and/or an absent or abnormally located anus (imperforate anus). Obstruction of the central portion of the small intestine (jejunal atresia) may occur due to twisting of the small intestine.Intellectual disability may be present in some individuals with Hanhart syndrome. | Symptoms of Hanhart Syndrome. The craniofacial abnormalities in children with Hanhart syndrome can include a small mouth (microstomia); small jaw and deeply receding jaw (micrognathia); shorty, incompletely developed tongue (hypoglossia); cleft palate; cleft tongue; broad nose; increased distance between the inner corners of the eyelids (telecanthus); lower eyelid defects; facial asymmetry; and partial absence of the jaw (mandibular hypodontia).Affected children may have fingers and/or toes that are partially missing or completely absent (ectrodactylia). In addition, lower (distal) portions of the arms and/or legs may be malformed, partially missing, and/or completely absent (amelia). Limb malformations may vary in severity from limb to limb (asymmetric).Infants with Hanhart syndrome may have loss of some motor function (paralysis) in the facial area at birth due to impairment of one or more of the 12 nerve pairs that arise from the brain (cranial nerve palsy). In many cases, congenital nerve palsy of the 6th (abducens) and/or 7th (facialis) cranial nerves is present. In rarer cases, the 3rd (oculomotorius), 5th (trigeminus), 9th (glossopharyngeus), and/or 12th (hypoglossus) cranial nerves are affected. The presence of some of these nerve palsies can worsen any feeding problems that occur because of tongue, mouth, and/or jaw abnormalities.Additional abnormalities may occur in association with Hanhart syndrome. In some affected individuals, the spleen and the gonads (i.e., testes in males, ovaries in females) may have fused together during fetal development (splenogonadal fusion). This may be manifested in males as a testicular mass or as a testis that has failed to descend into the scrotum (cryptorchidism). Some individuals may have vertical skin folds that cover the inner corners of the eyes (epicanthus); a malformation of the foot (clubfoot or talipes); an absent kidney (unilateral renal agenesis); a cyst in the brain (porencephalic cyst); and/or an absent or abnormally located anus (imperforate anus). Obstruction of the central portion of the small intestine (jejunal atresia) may occur due to twisting of the small intestine.Intellectual disability may be present in some individuals with Hanhart syndrome. | 551 | Hanhart Syndrome |
nord_551_2 | Causes of Hanhart Syndrome | The exact cause of Hanhart syndrome is not known. Cases tend to occur randomly, with no apparent cause (sporadic). Some researchers believe that the disorder, which has been reported in the children of blood relatives (consanguinity) in a number of cases, may be inherited in an autosomal recessive pattern.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.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.Some clinicians theorize that the defect in development responsible for Hanhart syndrome may occur when there is an hemorrhagic lesion or an interruption of the necessary blood supply to the parts of the embryo that eventually develop into the arms, legs, hands, and feet (the limb buds); the tongue; the mouth and jaw area (Meckel’s cartilage); and, possibly in some cases, parts of the brain. It is projected that a clot has formed within a blood vessel (thrombus) or has traveled through the blood stream and become lodged in a vessel (embolus) is responsible for the interruption of blood flow. Such a clot may result from exposure of the embryo to certain drugs taken during pregnancy that decrease blood flow (hypoperfusion) through particular organs. Or a clot could result from the death of another embryo in the uterus that was originally formed from the same fertilized egg (discordant monozygotic twins). | Causes of Hanhart Syndrome. The exact cause of Hanhart syndrome is not known. Cases tend to occur randomly, with no apparent cause (sporadic). Some researchers believe that the disorder, which has been reported in the children of blood relatives (consanguinity) in a number of cases, may be inherited in an autosomal recessive pattern.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.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.Some clinicians theorize that the defect in development responsible for Hanhart syndrome may occur when there is an hemorrhagic lesion or an interruption of the necessary blood supply to the parts of the embryo that eventually develop into the arms, legs, hands, and feet (the limb buds); the tongue; the mouth and jaw area (Meckel’s cartilage); and, possibly in some cases, parts of the brain. It is projected that a clot has formed within a blood vessel (thrombus) or has traveled through the blood stream and become lodged in a vessel (embolus) is responsible for the interruption of blood flow. Such a clot may result from exposure of the embryo to certain drugs taken during pregnancy that decrease blood flow (hypoperfusion) through particular organs. Or a clot could result from the death of another embryo in the uterus that was originally formed from the same fertilized egg (discordant monozygotic twins). | 551 | Hanhart Syndrome |
nord_551_3 | Affects of Hanhart Syndrome | Hanhart syndrome is a very rare developmental disorder that affects males and females in equal numbers. Fewer than 1 in 20,000 children are affected with this disorder. Approximately 30 cases of Hanhart syndrome were reported in the medical literature from 1932 to 1991. | Affects of Hanhart Syndrome. Hanhart syndrome is a very rare developmental disorder that affects males and females in equal numbers. Fewer than 1 in 20,000 children are affected with this disorder. Approximately 30 cases of Hanhart syndrome were reported in the medical literature from 1932 to 1991. | 551 | Hanhart Syndrome |
nord_551_4 | Related disorders of Hanhart Syndrome | Symptoms of the following disorders can be similar to those of Hanhart syndrome. Comparisons may be useful for a differential diagnosis:Oromandibular-limb hypogenesis syndrome is the name sometimes used to describe a group of rare disorders that are all characterized by underdevelopment (hypogenesis) of the mouth and jaw (oromandibular) areas, the limb buds, and possibly other areas in the developing embryo. This group of disorders includes Hanhart syndrome, ankyloglossum superiorsyndrome, Charlie M syndrome, and Moebius syndrome. Some researchers believe that these are overlapping disorders or disease variants representing a spectrum of malformations caused by environmental or other factors.Ankyloglossum superior syndrome is a rare developmental disorder in which part of the tongue is joined to the roof of the mouth (palate), causing restricted movement of the tongue and difficulty with speech. The disorder is also characterized by malformations of the arms, legs, hands, and/or feet. Although the exact cause of ankyloglossum superior syndrome is not known, it is believed that genetic and/or environmental factors may play a role.Charlie M syndrome is a rare birth defect characterized by distinctive facial abnormalities in association with malformations of the arms, legs, hands, and/or feet. Facial abnormalities may include eyes that are set widely apart (ocular hypertelorism), a broad nose and small mouth, incomplete closure of the roof of the mouth (cleft palate), an abnormally small jaw (micrognathia), and dental abnormalities, including front teeth (incisors) that are absent (hypodontia) or appear to be cone-shaped (conical). Affected individuals may also have a short, incompletely developed tongue (hypoglossia), a vertical groove in the front of the tongue (cleft tongue), and/or some degree of facial nerve paralysis (cranial nerve palsy). Lower (distal) portions of the arms, legs, hands, and/or feet may be malformed, partially missing, and/or absent. Some individuals with Charlie M syndrome may also exhibit the main characteristics of Poland syndrome. (For information on Poland syndrome, see the end of this section.) The exact cause of Charlie M syndrome is not known. Some researchers believe that the syndrome may be inherited in an X-linked pattern or may be caused by the interaction of several genes (polygenic inheritance).Moebius syndrome is a rare neurological disorder characterized by weakness or paralysis (palsy) of multiple cranial nerves, most often the 6th (abducens) and 7th (facial) nerves. Other cranial nerves are sometimes affected. The disorder is present at birth (congenital). If the 7th nerve is involved, the individual with Moebius syndrome is unable to smile, frown, pucker the lips, raise the eyebrows, or close the eyelids. If the 6th nerve is affected, the eye cannot turn outward past the midline. Other abnormalities include underdevelopment of the pectoral muscles and defects of the limbs. Moebius syndrome is not progressive. The exact cause is unknown. It appears to occur randomly (sporadically) in most cases; however, some cases occur in families suggesting that there may be a genetic component. (For more information on this disorder, choose “Moebius” as your search term in the Rare Disease Database.)Poland syndrome is a rare condition that is evident at birth (congenital). Associated features may be extremely variable from person to person. However, it is classically characterized by absence (aplasia) of chest wall muscles on one side of the body (unilateral) and abnormally short, webbed fingers (symbrachydactyly) of the hand on the same side (ipsilateral). In those with the condition, there is typically unilateral absence of the pectoralis minor and the sternal or breastbone portion of the pectoralis major. The pectoralis minor is a thin, triangular muscle of the upper chest wall; the pectoralis major is a large, fanlike muscle that covers most of the upper, front part of the chest. Affected individuals may have variable associated features, such as underdevelopment or absence of one nipple (including the darkened area around the nipple [areola]) and/or patchy absence of hair under the arm (axilla). In females, there may be underdevelopment or absence (aplasia) of one breast and underlying (subcutaneous) tissues. In some cases, associated skeletal abnormalities may also be present, such as underdevelopment or absence of upper ribs; elevation of the shoulder blade (Sprengel deformity); and/or shortening of the arm, with underdevelopment of the forearm bones (i.e., ulna and radius). Poland syndrome affects males more commonly than females and most frequently involves the right side of the body. The exact cause of the condition is unknown. (For more information on this disorder, choose “Poland” as your search term in the Rare Disease Database.)In Poland-Moebius syndrome, the developmental abnormalities associated with Poland syndrome occur in conjunction with facial paralysis due to impairment of the 6th and/or 7th cranial nerves, as occurs in Moebius syndrome. The exact cause of Poland-Moebius syndrome is not known.Phocomelia is primarily characterized by deficient limb development. In most affected children, parts of the hands and arms may be malformed or missing; malformations of portions of the legs may also be present in some cases. The hands and/or feet may be attached close to the body, or the limbs may be abnormally small. Other physical abnormalities may include a swelling or mass of blood vessels (hemangioma) on the face; abnormalities of the eyes, ears, and/or nose; testes that have failed to descend (cryptorchidism); and/or malformations of several internal organs. In some children, intellectual disability may also be present. Phocomelia may occur randomly for no apparent reason (sporadic), may be inherited in an autosomal recessive pattern, or may be caused by the ingestion of certain drugs during early pregnancy such as thalidomide. | Related disorders of Hanhart Syndrome. Symptoms of the following disorders can be similar to those of Hanhart syndrome. Comparisons may be useful for a differential diagnosis:Oromandibular-limb hypogenesis syndrome is the name sometimes used to describe a group of rare disorders that are all characterized by underdevelopment (hypogenesis) of the mouth and jaw (oromandibular) areas, the limb buds, and possibly other areas in the developing embryo. This group of disorders includes Hanhart syndrome, ankyloglossum superiorsyndrome, Charlie M syndrome, and Moebius syndrome. Some researchers believe that these are overlapping disorders or disease variants representing a spectrum of malformations caused by environmental or other factors.Ankyloglossum superior syndrome is a rare developmental disorder in which part of the tongue is joined to the roof of the mouth (palate), causing restricted movement of the tongue and difficulty with speech. The disorder is also characterized by malformations of the arms, legs, hands, and/or feet. Although the exact cause of ankyloglossum superior syndrome is not known, it is believed that genetic and/or environmental factors may play a role.Charlie M syndrome is a rare birth defect characterized by distinctive facial abnormalities in association with malformations of the arms, legs, hands, and/or feet. Facial abnormalities may include eyes that are set widely apart (ocular hypertelorism), a broad nose and small mouth, incomplete closure of the roof of the mouth (cleft palate), an abnormally small jaw (micrognathia), and dental abnormalities, including front teeth (incisors) that are absent (hypodontia) or appear to be cone-shaped (conical). Affected individuals may also have a short, incompletely developed tongue (hypoglossia), a vertical groove in the front of the tongue (cleft tongue), and/or some degree of facial nerve paralysis (cranial nerve palsy). Lower (distal) portions of the arms, legs, hands, and/or feet may be malformed, partially missing, and/or absent. Some individuals with Charlie M syndrome may also exhibit the main characteristics of Poland syndrome. (For information on Poland syndrome, see the end of this section.) The exact cause of Charlie M syndrome is not known. Some researchers believe that the syndrome may be inherited in an X-linked pattern or may be caused by the interaction of several genes (polygenic inheritance).Moebius syndrome is a rare neurological disorder characterized by weakness or paralysis (palsy) of multiple cranial nerves, most often the 6th (abducens) and 7th (facial) nerves. Other cranial nerves are sometimes affected. The disorder is present at birth (congenital). If the 7th nerve is involved, the individual with Moebius syndrome is unable to smile, frown, pucker the lips, raise the eyebrows, or close the eyelids. If the 6th nerve is affected, the eye cannot turn outward past the midline. Other abnormalities include underdevelopment of the pectoral muscles and defects of the limbs. Moebius syndrome is not progressive. The exact cause is unknown. It appears to occur randomly (sporadically) in most cases; however, some cases occur in families suggesting that there may be a genetic component. (For more information on this disorder, choose “Moebius” as your search term in the Rare Disease Database.)Poland syndrome is a rare condition that is evident at birth (congenital). Associated features may be extremely variable from person to person. However, it is classically characterized by absence (aplasia) of chest wall muscles on one side of the body (unilateral) and abnormally short, webbed fingers (symbrachydactyly) of the hand on the same side (ipsilateral). In those with the condition, there is typically unilateral absence of the pectoralis minor and the sternal or breastbone portion of the pectoralis major. The pectoralis minor is a thin, triangular muscle of the upper chest wall; the pectoralis major is a large, fanlike muscle that covers most of the upper, front part of the chest. Affected individuals may have variable associated features, such as underdevelopment or absence of one nipple (including the darkened area around the nipple [areola]) and/or patchy absence of hair under the arm (axilla). In females, there may be underdevelopment or absence (aplasia) of one breast and underlying (subcutaneous) tissues. In some cases, associated skeletal abnormalities may also be present, such as underdevelopment or absence of upper ribs; elevation of the shoulder blade (Sprengel deformity); and/or shortening of the arm, with underdevelopment of the forearm bones (i.e., ulna and radius). Poland syndrome affects males more commonly than females and most frequently involves the right side of the body. The exact cause of the condition is unknown. (For more information on this disorder, choose “Poland” as your search term in the Rare Disease Database.)In Poland-Moebius syndrome, the developmental abnormalities associated with Poland syndrome occur in conjunction with facial paralysis due to impairment of the 6th and/or 7th cranial nerves, as occurs in Moebius syndrome. The exact cause of Poland-Moebius syndrome is not known.Phocomelia is primarily characterized by deficient limb development. In most affected children, parts of the hands and arms may be malformed or missing; malformations of portions of the legs may also be present in some cases. The hands and/or feet may be attached close to the body, or the limbs may be abnormally small. Other physical abnormalities may include a swelling or mass of blood vessels (hemangioma) on the face; abnormalities of the eyes, ears, and/or nose; testes that have failed to descend (cryptorchidism); and/or malformations of several internal organs. In some children, intellectual disability may also be present. Phocomelia may occur randomly for no apparent reason (sporadic), may be inherited in an autosomal recessive pattern, or may be caused by the ingestion of certain drugs during early pregnancy such as thalidomide. | 551 | Hanhart Syndrome |
nord_551_5 | Diagnosis of Hanhart Syndrome | Hanhart syndrome can be diagnosed in a newborn baby based upon a thorough clinical evaluation and characteristic physical findings. | Diagnosis of Hanhart Syndrome. Hanhart syndrome can be diagnosed in a newborn baby based upon a thorough clinical evaluation and characteristic physical findings. | 551 | Hanhart Syndrome |
nord_551_6 | Therapies of Hanhart Syndrome | Treatment
The treatment of Hanhart syndrome requires the coordinated efforts of a team of specialists. Pediatricians, plastic and orthopedic surgeons, dental specialists, speech pathologists, physical therapists, and others must systematically and comprehensively plan the child’s treatment.Infants with Hanhart syndrome may have feeding difficulties resulting from tongue, mouth, and/or jaw malformations and cranial nerve palsies that must be addressed immediately to ensure proper nutrition and growth. Abnormalities of the tongue, mouth, and jaw area may be treated through surgical correction, the use of artificial devices (prostheses) and/or physical therapy.
Children with Hanhart syndrome may benefit from speech therapy if speech is affected by tongue, mouth, and/or jaw malformations. Depending on the severity of any limb abnormalities, children with Hanhart syndrome may have difficulty performing skills that require coordination of motion (motor skills), such as walking, writing, etc. Treatment may consist of surgery; the use of artificial replacements for parts of the arms, legs, hands, and/or feet that may be missing (limb prostheses); and/or physical therapy to help individuals enhance their motor skills.Individuals with Hanhart syndrome may also benefit from special social support, special education, and vocational and occupational services. Other treatment is symptomatic and supportive, based upon the specifics of the affected individual’s case.Genetic counseling is recommended for patients and their families. | Therapies of Hanhart Syndrome. Treatment
The treatment of Hanhart syndrome requires the coordinated efforts of a team of specialists. Pediatricians, plastic and orthopedic surgeons, dental specialists, speech pathologists, physical therapists, and others must systematically and comprehensively plan the child’s treatment.Infants with Hanhart syndrome may have feeding difficulties resulting from tongue, mouth, and/or jaw malformations and cranial nerve palsies that must be addressed immediately to ensure proper nutrition and growth. Abnormalities of the tongue, mouth, and jaw area may be treated through surgical correction, the use of artificial devices (prostheses) and/or physical therapy.
Children with Hanhart syndrome may benefit from speech therapy if speech is affected by tongue, mouth, and/or jaw malformations. Depending on the severity of any limb abnormalities, children with Hanhart syndrome may have difficulty performing skills that require coordination of motion (motor skills), such as walking, writing, etc. Treatment may consist of surgery; the use of artificial replacements for parts of the arms, legs, hands, and/or feet that may be missing (limb prostheses); and/or physical therapy to help individuals enhance their motor skills.Individuals with Hanhart syndrome may also benefit from special social support, special education, and vocational and occupational services. Other treatment is symptomatic and supportive, based upon the specifics of the affected individual’s case.Genetic counseling is recommended for patients and their families. | 551 | Hanhart Syndrome |
nord_552_0 | Overview of Hantavirus Pulmonary Syndrome | Hantavirus pulmonary syndrome (HPS) is an infectious disease caused by hantaviruses (Sin Nombre hantavirus in most of the US). Transmission occurs when direct or indirect (airborne) contact is made with the saliva or waste products of rodents that carry the virus, most commonly the deer mouse (Peromyscus maniculatus). Initial symptoms may include fever, muscle aches (myalgias), headache, cough, and/or difficulty breathing. Symptoms progress rapidly, and abnormally low blood pressure (hypotension), shock, and/or respiratory failure may occur. | Overview of Hantavirus Pulmonary Syndrome. Hantavirus pulmonary syndrome (HPS) is an infectious disease caused by hantaviruses (Sin Nombre hantavirus in most of the US). Transmission occurs when direct or indirect (airborne) contact is made with the saliva or waste products of rodents that carry the virus, most commonly the deer mouse (Peromyscus maniculatus). Initial symptoms may include fever, muscle aches (myalgias), headache, cough, and/or difficulty breathing. Symptoms progress rapidly, and abnormally low blood pressure (hypotension), shock, and/or respiratory failure may occur. | 552 | Hantavirus Pulmonary Syndrome |
nord_552_1 | Symptoms of Hantavirus Pulmonary Syndrome | The initial symptoms of HPS most commonly include fever, muscle aches (myalgias), headache, and/or cough. Chills, abdominal pain, diarrhea, and/or a sense of overall discomfort (malaise) may be present. Other symptoms usually include shortness of breath, rapid breathing (tachypnea), rapid heartbeat (tachycardia), dizziness, and sometimes joint pain (arthralgia), back and/or chest pain, and/or sweating.Shortly after the initial symptoms of HPS appear excess fluid may accumulate in the lungs (pulmonary edema), beginning in the air spaces in the lungs (interstitial edema). Fluid may then fill the pockets in the lung tissue (alveolar edema) of both lungs (bilaterally) and cause difficulty in breathing and abnormally low levels of oxygen in the blood (hypoxemia). Accumulation of tissue and cells not normally found in the lungs (infiltrates) may also occur. The disease progresses rapidly and may cause abnormally low blood pressure (hypotension), shock, and/or respiratory distress. | Symptoms of Hantavirus Pulmonary Syndrome. The initial symptoms of HPS most commonly include fever, muscle aches (myalgias), headache, and/or cough. Chills, abdominal pain, diarrhea, and/or a sense of overall discomfort (malaise) may be present. Other symptoms usually include shortness of breath, rapid breathing (tachypnea), rapid heartbeat (tachycardia), dizziness, and sometimes joint pain (arthralgia), back and/or chest pain, and/or sweating.Shortly after the initial symptoms of HPS appear excess fluid may accumulate in the lungs (pulmonary edema), beginning in the air spaces in the lungs (interstitial edema). Fluid may then fill the pockets in the lung tissue (alveolar edema) of both lungs (bilaterally) and cause difficulty in breathing and abnormally low levels of oxygen in the blood (hypoxemia). Accumulation of tissue and cells not normally found in the lungs (infiltrates) may also occur. The disease progresses rapidly and may cause abnormally low blood pressure (hypotension), shock, and/or respiratory distress. | 552 | Hantavirus Pulmonary Syndrome |
nord_552_2 | Causes of Hantavirus Pulmonary Syndrome | HPS in the US is mostly caused by Sin Nombre Hantavirus, a newly identified virus within the Bunyaviridae family. The virus is carried by the deer mouse (Peromyscus maniculatus). The deer mouse can be found in most parts of the United States, except the southeast. Not all deer mice are infected with Sin Nombre hantavirus, and those that do carry the virus do not appear to be affected by any associated disease.Three other species of hantavirus are causing human disease in the US: New York Virus identified in the white-footed mouse (eastern US), Black Creek Canal virus in cotton rat in Florida, and Bayou virus in Rice Field Mice in Texas and Louisiana. In addition, many other hantaviruses have been found in other rodent species in several States but were never detected in humans. In South America, numerous hantaviruses have been found responsible of human diseases. Andes virus is the cause of very severe HPS in Argentina and Chile.Sin Nombre hantavirus is transmitted to humans when they come in direct or indirect (airborne) contact with waste products or saliva from an infected rodent. Respiratory transmission, thought to be the most frequent mode of transmission of Sin Nombre hantavirus, occurs when an individual inhales airborne particles of dust or dried particles that carry saliva or waste products from an infected rodent. Infectious virus particles could also penetrate through the mucosa. | Causes of Hantavirus Pulmonary Syndrome. HPS in the US is mostly caused by Sin Nombre Hantavirus, a newly identified virus within the Bunyaviridae family. The virus is carried by the deer mouse (Peromyscus maniculatus). The deer mouse can be found in most parts of the United States, except the southeast. Not all deer mice are infected with Sin Nombre hantavirus, and those that do carry the virus do not appear to be affected by any associated disease.Three other species of hantavirus are causing human disease in the US: New York Virus identified in the white-footed mouse (eastern US), Black Creek Canal virus in cotton rat in Florida, and Bayou virus in Rice Field Mice in Texas and Louisiana. In addition, many other hantaviruses have been found in other rodent species in several States but were never detected in humans. In South America, numerous hantaviruses have been found responsible of human diseases. Andes virus is the cause of very severe HPS in Argentina and Chile.Sin Nombre hantavirus is transmitted to humans when they come in direct or indirect (airborne) contact with waste products or saliva from an infected rodent. Respiratory transmission, thought to be the most frequent mode of transmission of Sin Nombre hantavirus, occurs when an individual inhales airborne particles of dust or dried particles that carry saliva or waste products from an infected rodent. Infectious virus particles could also penetrate through the mucosa. | 552 | Hantavirus Pulmonary Syndrome |
nord_552_3 | Affects of Hantavirus Pulmonary Syndrome | HPS appears to affect males and females in equal numbers. Approximately half of the cases reported in the medical literature have affected Native Americans, and the majority of the remaining reported cases affected Caucasians. The population affected by HPS appears to be related to geographic location and exposure to rodent droppings as opposed to ethnic background. Because many of the documented cases have occurred in the southwestern United States, a high percentage of the initially affected individuals were Native Americans. As the virus was found in others parts of the US, many others of varied ethnic backgrounds have been affected throughout the United States. | Affects of Hantavirus Pulmonary Syndrome. HPS appears to affect males and females in equal numbers. Approximately half of the cases reported in the medical literature have affected Native Americans, and the majority of the remaining reported cases affected Caucasians. The population affected by HPS appears to be related to geographic location and exposure to rodent droppings as opposed to ethnic background. Because many of the documented cases have occurred in the southwestern United States, a high percentage of the initially affected individuals were Native Americans. As the virus was found in others parts of the US, many others of varied ethnic backgrounds have been affected throughout the United States. | 552 | Hantavirus Pulmonary Syndrome |
nord_552_4 | Related disorders of Hantavirus Pulmonary Syndrome | Symptoms of the following disorders can be similar to those of Hantavirus Pulmonary Syndrome. Comparisons may be useful for a differential diagnosis:There are many types of pneumonia that can be caused by bacteria or virus. In general the symptoms of pneumonia are similar to those of Hantavirus Pulmonary Syndrome. Only laboratory testing can determine which disease is affecting an individual.Interstitial pneumonia, involving the spaces and tissue (interstices) of the lungs, is a type of primary pneumonia. It involves an abnormal increase in the interstitial tissue and a decrease and hardening (induration) of other lung tissue. Major symptoms may include shortness of breath on exertion, cough (which may or may not be present), and loss of appetite. Symptoms of interstitial pneumonia may vary from mild to severe according to the extent of lung involvement, accumulation of tissue and cells not normally found in the lungs (infiltrate), the rate of progress, and the presence of complications (such as other lung infections). The patient often has no fever (afebrile). However, occasionally the onset may be rapid, with fever, suggesting an acute respiratory infection. (For more information on this disorder, choose “Interstitial Pneumonia” as your search term in the Rare Disease Database.)Eosinophilic pneumonia is characterized by an inflammation of the lungs and an abnormal increase in the number of certain white blood cells (eosinophils) in the lymph nodes, lungs, and blood. This disorder is usually associated with allergic conditions and various parasitic infections. Eosinophilic pneumonia usually has a sudden onset. There may be accompanying weight loss and increased pulse rate. Symptoms may also include low-grade fever, cough with the possibility of blood in the phlegm, wheezing and labored breathing. There may also be chills, sweating, chest pain, and/or a general feeling of ill health. The symptoms of eosinophilic pneumonia may be mild or severe, depending upon the amount of lung area affected. (For more information on this disorder, choose “Eosinophilic Pneumonia” as your search term in the Rare Disease Database.) | Related disorders of Hantavirus Pulmonary Syndrome. Symptoms of the following disorders can be similar to those of Hantavirus Pulmonary Syndrome. Comparisons may be useful for a differential diagnosis:There are many types of pneumonia that can be caused by bacteria or virus. In general the symptoms of pneumonia are similar to those of Hantavirus Pulmonary Syndrome. Only laboratory testing can determine which disease is affecting an individual.Interstitial pneumonia, involving the spaces and tissue (interstices) of the lungs, is a type of primary pneumonia. It involves an abnormal increase in the interstitial tissue and a decrease and hardening (induration) of other lung tissue. Major symptoms may include shortness of breath on exertion, cough (which may or may not be present), and loss of appetite. Symptoms of interstitial pneumonia may vary from mild to severe according to the extent of lung involvement, accumulation of tissue and cells not normally found in the lungs (infiltrate), the rate of progress, and the presence of complications (such as other lung infections). The patient often has no fever (afebrile). However, occasionally the onset may be rapid, with fever, suggesting an acute respiratory infection. (For more information on this disorder, choose “Interstitial Pneumonia” as your search term in the Rare Disease Database.)Eosinophilic pneumonia is characterized by an inflammation of the lungs and an abnormal increase in the number of certain white blood cells (eosinophils) in the lymph nodes, lungs, and blood. This disorder is usually associated with allergic conditions and various parasitic infections. Eosinophilic pneumonia usually has a sudden onset. There may be accompanying weight loss and increased pulse rate. Symptoms may also include low-grade fever, cough with the possibility of blood in the phlegm, wheezing and labored breathing. There may also be chills, sweating, chest pain, and/or a general feeling of ill health. The symptoms of eosinophilic pneumonia may be mild or severe, depending upon the amount of lung area affected. (For more information on this disorder, choose “Eosinophilic Pneumonia” as your search term in the Rare Disease Database.) | 552 | Hantavirus Pulmonary Syndrome |
nord_552_5 | Diagnosis of Hantavirus Pulmonary Syndrome | Diagnosis of Hantavirus Pulmonary Syndrome. | 552 | Hantavirus Pulmonary Syndrome |
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nord_552_6 | Therapies of Hantavirus Pulmonary Syndrome | It is important to avoid areas where deer mice leave their droppings, such as storage sheds, basements, and wood piles. When exposed to mouse droppings, an individual should wear a face mask that covers both nose and mouth, as well as rubber gloves. The area should be sanitized with disinfectant to avoid aerosolization of potentially infected dust. People who exhibit flu-like symptoms after exposure to mouse droppings should be taken to a hospital immediately, because this disorder progresses over a matter of hours, and every hour is crucial.The diagnosis of HPS depends on several factors, including the symptoms of the affected individual, a history of contact with rodents (especially deer mice) or exposure to areas where rodents may live, the lack of any alternative diagnosis, and/or laboratory tests that show characteristic changes. Because the symptoms of HPS are rapidly progressive, immediate aggressive care is indicated if HPS is suspected.Characteristic laboratory blood test results for people with HPS may show abnormally enlarged white blood cells (atypical lymphocytes), a platelet count that is lower than normal (thrombocytopenia) or dropping, and/or a higher than normal white blood cell count. Oxygen levels in blood and/or tissue may be extremely low (hypoxemia).The diagnosis of HPS is confirmed when laboratory tests reveal the presence and/or increased levels of certain proteins (Hantavirus IgM and/or a rising IgG titer) in blood samples from affected individuals. A process called polymerase chain reaction (PCR) may be used to detect a hantavirus and identify which strain has caused the infection.Treatment of HPS involves intensive care, including the monitoring of fluid balances, electrolyte balances, and blood pressure. Abnormally low levels of oxygen in the blood (hypoxemia) may require the administration of oxygen. Shock and low blood pressure (hypotension) associated with HPS may be treated with drugs (i.e., dopamine and norepinephrine) to increase blood flow and thus improve blood and oxygen delivery to organs. In severe patients, Extra Corporeal Membrane Oxygenation (ECMO) therapy could be offered in specialized centers and may be the only chance of survival. | Therapies of Hantavirus Pulmonary Syndrome. It is important to avoid areas where deer mice leave their droppings, such as storage sheds, basements, and wood piles. When exposed to mouse droppings, an individual should wear a face mask that covers both nose and mouth, as well as rubber gloves. The area should be sanitized with disinfectant to avoid aerosolization of potentially infected dust. People who exhibit flu-like symptoms after exposure to mouse droppings should be taken to a hospital immediately, because this disorder progresses over a matter of hours, and every hour is crucial.The diagnosis of HPS depends on several factors, including the symptoms of the affected individual, a history of contact with rodents (especially deer mice) or exposure to areas where rodents may live, the lack of any alternative diagnosis, and/or laboratory tests that show characteristic changes. Because the symptoms of HPS are rapidly progressive, immediate aggressive care is indicated if HPS is suspected.Characteristic laboratory blood test results for people with HPS may show abnormally enlarged white blood cells (atypical lymphocytes), a platelet count that is lower than normal (thrombocytopenia) or dropping, and/or a higher than normal white blood cell count. Oxygen levels in blood and/or tissue may be extremely low (hypoxemia).The diagnosis of HPS is confirmed when laboratory tests reveal the presence and/or increased levels of certain proteins (Hantavirus IgM and/or a rising IgG titer) in blood samples from affected individuals. A process called polymerase chain reaction (PCR) may be used to detect a hantavirus and identify which strain has caused the infection.Treatment of HPS involves intensive care, including the monitoring of fluid balances, electrolyte balances, and blood pressure. Abnormally low levels of oxygen in the blood (hypoxemia) may require the administration of oxygen. Shock and low blood pressure (hypotension) associated with HPS may be treated with drugs (i.e., dopamine and norepinephrine) to increase blood flow and thus improve blood and oxygen delivery to organs. In severe patients, Extra Corporeal Membrane Oxygenation (ECMO) therapy could be offered in specialized centers and may be the only chance of survival. | 552 | Hantavirus Pulmonary Syndrome |
nord_553_0 | Overview of Harlequin Ichthyosis | Harlequin ichthyosis is a rare genetic skin disorder. The newborn infant is covered with plates of thick skin that crack and split apart. The thick plates can pull at and distort facial features and can restrict breathing and eating. Harlequin infants need to be cared for in the neonatal intensive care unit immediately. Harlequin ichthyosis is inherited in an autosomal recessive pattern. | Overview of Harlequin Ichthyosis. Harlequin ichthyosis is a rare genetic skin disorder. The newborn infant is covered with plates of thick skin that crack and split apart. The thick plates can pull at and distort facial features and can restrict breathing and eating. Harlequin infants need to be cared for in the neonatal intensive care unit immediately. Harlequin ichthyosis is inherited in an autosomal recessive pattern. | 553 | Harlequin Ichthyosis |
nord_553_1 | Symptoms of Harlequin Ichthyosis | Infants with Harlequin ichthyosis are covered in thick plate-like scales of skin. The tightness of the skin pulls around the eyes and the mouth, forcing the eyelids and lips to turn inside out, revealing the red inner linings. The chest and abdomen of the infant may be severely restricted by the tightness of the skin, making breathing and eating difficult. The hands and feet may be small and swollen, and partially flexed. The ears may appear to be misshapen or missing, but are really fused to the head by the thick skin. Infants born with harlequin ichthyosis may also have a flat nose (depressed nasal bridge), abnormal hearing, frequent respiratory infections, and decreased joint mobility.Premature birth is typical, leaving the infants at risk for complications from early delivery. These infants are also at high risk for low body temperature, dehydration, and hypernatremia (elevated levels of sodium in the blood). Constriction and swelling of the mouth may interfere with the suck response and infants may need tube feeding. The baby’s corneas need to be lubricated and protected if the eyelids are forced open by the tightness of the skin. | Symptoms of Harlequin Ichthyosis. Infants with Harlequin ichthyosis are covered in thick plate-like scales of skin. The tightness of the skin pulls around the eyes and the mouth, forcing the eyelids and lips to turn inside out, revealing the red inner linings. The chest and abdomen of the infant may be severely restricted by the tightness of the skin, making breathing and eating difficult. The hands and feet may be small and swollen, and partially flexed. The ears may appear to be misshapen or missing, but are really fused to the head by the thick skin. Infants born with harlequin ichthyosis may also have a flat nose (depressed nasal bridge), abnormal hearing, frequent respiratory infections, and decreased joint mobility.Premature birth is typical, leaving the infants at risk for complications from early delivery. These infants are also at high risk for low body temperature, dehydration, and hypernatremia (elevated levels of sodium in the blood). Constriction and swelling of the mouth may interfere with the suck response and infants may need tube feeding. The baby’s corneas need to be lubricated and protected if the eyelids are forced open by the tightness of the skin. | 553 | Harlequin Ichthyosis |
nord_553_2 | Causes of Harlequin Ichthyosis | Harlequin ichthyosis is caused by changes (mutations) in the ABCA12 gene, which gives instructions for making a protein that is necessary for skin cells to develop normally. It plays a key role in the transport of fats (lipids) to most superficial layer of the skin (epidermis), creating an effective skin barrier. When this gene is mutated, the skin barrier is disrupted.Harlequin ichthyosis is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females. | Causes of Harlequin Ichthyosis. Harlequin ichthyosis is caused by changes (mutations) in the ABCA12 gene, which gives instructions for making a protein that is necessary for skin cells to develop normally. It plays a key role in the transport of fats (lipids) to most superficial layer of the skin (epidermis), creating an effective skin barrier. When this gene is mutated, the skin barrier is disrupted.Harlequin ichthyosis is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females. | 553 | Harlequin Ichthyosis |
nord_553_3 | Affects of Harlequin Ichthyosis | Harlequin ichthyosis affects males and females in equal numbers. This condition affects approximately one in 500,000 persons or about seven births annually in the United States. | Affects of Harlequin Ichthyosis. Harlequin ichthyosis affects males and females in equal numbers. This condition affects approximately one in 500,000 persons or about seven births annually in the United States. | 553 | Harlequin Ichthyosis |
nord_553_4 | Related disorders of Harlequin Ichthyosis | Symptoms of the following disorder may be similar to harlequin ichthyosis.Lamellar ichthyosis is an inherited skin disorder characterized by broad, dark, plate-like scales separated by deep cracks. Lamellar ichthyosis may also cause reddened skin (erythroderma), thickened skin on the palms and soles and decreased sweating with heat intolerance. (For more information on lamellar ichthyosis, choose “Ichthyosis, Lamellar” as your search term in the Rare Disease Database.) | Related disorders of Harlequin Ichthyosis. Symptoms of the following disorder may be similar to harlequin ichthyosis.Lamellar ichthyosis is an inherited skin disorder characterized by broad, dark, plate-like scales separated by deep cracks. Lamellar ichthyosis may also cause reddened skin (erythroderma), thickened skin on the palms and soles and decreased sweating with heat intolerance. (For more information on lamellar ichthyosis, choose “Ichthyosis, Lamellar” as your search term in the Rare Disease Database.) | 553 | Harlequin Ichthyosis |
nord_553_5 | Diagnosis of Harlequin Ichthyosis | Harlequin ichthyosis is diagnosed at birth based on the child’s physical appearance. Prenatal testing may be possible by testing fetal DNA for mutations in the ABCA12 gene. In addition, some of the features of harlequin ichthyosis maybe seen on ultrasound during the second trimester and onward. | Diagnosis of Harlequin Ichthyosis. Harlequin ichthyosis is diagnosed at birth based on the child’s physical appearance. Prenatal testing may be possible by testing fetal DNA for mutations in the ABCA12 gene. In addition, some of the features of harlequin ichthyosis maybe seen on ultrasound during the second trimester and onward. | 553 | Harlequin Ichthyosis |
nord_553_6 | Therapies of Harlequin Ichthyosis | A multi-disciplinary team is involved in the care of infants with harlequin ichthyosis as soon as they are born. This has been shown to improve outcomes and reduce complications such as respiratory distress, dehydration, electrolyte imbalances, impaired thermoregulation, systemic bacterial infections, and feeding difficulties. Early treatment with oral retinoids is also thought to improve outcomes. However, they are only used in severe cases due to their known toxicity and side effects.The thick, plate-like skin of harlequin type ichthyosis will gradually split and peel off over several weeks. Antibiotic treatment may be necessary to prevent infection at this time. Administration of oral acitretin may accelerate shedding of the thick scales. Most harlequin infants will need one-on-one nursing care for the first several weeks of life.After the thick plates peel off, the skin is left dry and reddened, and may be covered in large thin scales. The skin symptoms are treated by applying skin softening emollients. This can be particularly effective after bathing while the skin is still moist. Many patients with severe ichthyosis exfoliate manually by rubbing off the thick scale with special exfoliating gloves with a rough surface. Skin barrier repair formulas containing ceramides or cholesterol, moisturizers with petrolatum or lanolin, and mild keratolytics (products containing alpha-hydroxy acids or urea) can all work to keep the skin moisturized and pliable, and prevent cracking and fissuring that can lead to infection. Removal of damaged tissue (debridement) from the fingers may be needed if they are constricted by bands of skin to avoid a loss of circulation. | Therapies of Harlequin Ichthyosis. A multi-disciplinary team is involved in the care of infants with harlequin ichthyosis as soon as they are born. This has been shown to improve outcomes and reduce complications such as respiratory distress, dehydration, electrolyte imbalances, impaired thermoregulation, systemic bacterial infections, and feeding difficulties. Early treatment with oral retinoids is also thought to improve outcomes. However, they are only used in severe cases due to their known toxicity and side effects.The thick, plate-like skin of harlequin type ichthyosis will gradually split and peel off over several weeks. Antibiotic treatment may be necessary to prevent infection at this time. Administration of oral acitretin may accelerate shedding of the thick scales. Most harlequin infants will need one-on-one nursing care for the first several weeks of life.After the thick plates peel off, the skin is left dry and reddened, and may be covered in large thin scales. The skin symptoms are treated by applying skin softening emollients. This can be particularly effective after bathing while the skin is still moist. Many patients with severe ichthyosis exfoliate manually by rubbing off the thick scale with special exfoliating gloves with a rough surface. Skin barrier repair formulas containing ceramides or cholesterol, moisturizers with petrolatum or lanolin, and mild keratolytics (products containing alpha-hydroxy acids or urea) can all work to keep the skin moisturized and pliable, and prevent cracking and fissuring that can lead to infection. Removal of damaged tissue (debridement) from the fingers may be needed if they are constricted by bands of skin to avoid a loss of circulation. | 553 | Harlequin Ichthyosis |
nord_554_0 | Overview of Hartnup Disease | Hartnup disease is a rare genetic disorder that involves an inborn error of amino acid metabolism. The disorder is characterized by a distinctive skin rash and in a few reported cases was accompanied by episodes of neurological involvement that can include an inability to coordinate voluntary movements (ataxia), vision problems, and cognitive delays. The symptoms associated with this disorder may be triggered by fever, drugs, or during situations when an affected individual is under emotional or physical stress such as during an illness. Generally, the frequency of such episodes usually diminishes with age. Hartnup disease is caused by mutations in the SLC6A19 gene and is inherited in an autosomal recessive manner. | Overview of Hartnup Disease. Hartnup disease is a rare genetic disorder that involves an inborn error of amino acid metabolism. The disorder is characterized by a distinctive skin rash and in a few reported cases was accompanied by episodes of neurological involvement that can include an inability to coordinate voluntary movements (ataxia), vision problems, and cognitive delays. The symptoms associated with this disorder may be triggered by fever, drugs, or during situations when an affected individual is under emotional or physical stress such as during an illness. Generally, the frequency of such episodes usually diminishes with age. Hartnup disease is caused by mutations in the SLC6A19 gene and is inherited in an autosomal recessive manner. | 554 | Hartnup Disease |
nord_554_1 | Symptoms of Hartnup Disease | The symptoms of Hartnup disease vary greatly from one person to another. The majority of affected individuals do not have any apparent symptoms (asymptomatic). When symptoms do develop, they most often occur between the ages of 3-9. In rare instances, symptoms first appear in adulthood.The most common symptom are red, scaly light-sensitive (photosensitive) rashes on the face, arms, extremities, and other exposed areas of skin.A wide variety of neurological abnormalities can occur including sudden episodes of impaired muscle coordination (ataxia), an unsteady walk (gait), impaired articulation of speech (dysarthria), occasional tremors of the hands and tongue, and spasticity, a condition marked by increased muscle tone and stiffness of the muscles, particularly those of the legs.There have been reports of delayed cognitive development and, in rare instances, mild intellectual disability in some children. It is, however, unclear whether these symptoms are related to Hartnup disorder or incidentally occurred in the same individual and were therefore attributed to Hartnup disorder. Similarly, seizures, fainting, trembling, lack of muscle tone (hypotonia), headaches, dizziness and/or vertigo, and delays in motor development have been observed but may be unrelated. Some affected individuals may experience psychiatric abnormalities including emotional instability such as rapid mood changes, depression, confusion, anxiety, delusions, and/or hallucinations.Some children experience growth delays and may be shorter than would be expected based upon age and gender (short stature). In some instances, the eyes may be affected and individuals may experience double vision (diplopia), involuntary rhythmic movements of the eyes (nystagmus), and droopy upper eyelids (ptosis).Diarrhea may precede or follow an episode of this disorder. Some adults with Hartnup disease have been reported whose initial symptom was the onset of seizures during adulthood. Heartburn has been reported in adults with the disorder. | Symptoms of Hartnup Disease. The symptoms of Hartnup disease vary greatly from one person to another. The majority of affected individuals do not have any apparent symptoms (asymptomatic). When symptoms do develop, they most often occur between the ages of 3-9. In rare instances, symptoms first appear in adulthood.The most common symptom are red, scaly light-sensitive (photosensitive) rashes on the face, arms, extremities, and other exposed areas of skin.A wide variety of neurological abnormalities can occur including sudden episodes of impaired muscle coordination (ataxia), an unsteady walk (gait), impaired articulation of speech (dysarthria), occasional tremors of the hands and tongue, and spasticity, a condition marked by increased muscle tone and stiffness of the muscles, particularly those of the legs.There have been reports of delayed cognitive development and, in rare instances, mild intellectual disability in some children. It is, however, unclear whether these symptoms are related to Hartnup disorder or incidentally occurred in the same individual and were therefore attributed to Hartnup disorder. Similarly, seizures, fainting, trembling, lack of muscle tone (hypotonia), headaches, dizziness and/or vertigo, and delays in motor development have been observed but may be unrelated. Some affected individuals may experience psychiatric abnormalities including emotional instability such as rapid mood changes, depression, confusion, anxiety, delusions, and/or hallucinations.Some children experience growth delays and may be shorter than would be expected based upon age and gender (short stature). In some instances, the eyes may be affected and individuals may experience double vision (diplopia), involuntary rhythmic movements of the eyes (nystagmus), and droopy upper eyelids (ptosis).Diarrhea may precede or follow an episode of this disorder. Some adults with Hartnup disease have been reported whose initial symptom was the onset of seizures during adulthood. Heartburn has been reported in adults with the disorder. | 554 | Hartnup Disease |
nord_554_2 | Causes of Hartnup Disease | Hartnup disease is caused by alterations (mutations) in the SLC6A19 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.These alterations are inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, 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.The SLC6A19 gene produces a protein known as an amino acid transporter, which serves to assist the movement (or transport) of specific amino acids within the body. This protein is especially active within the kidneys and the intestines, although these organs are otherwise unaffected and function normally. The amino acids affected include tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine, and valine.Amino acids are the chemical building blocks of proteins and are essential for proper growth and development. Because of the underlying genetic defect in Hartnup disease, the intestines cannot properly absorb amino acids and the kidney cannot properly reabsorb them, leading to excessive amounts of amino acids being lost through the passage of urine. This leaves the body with reduced amounts of amino acids to serve as the building blocks of proteins. Deficiency of the amino acid tryptophan is believed to account for the symptoms associated with Hartnup disease. Tryptophan is essential for the creation (synthesis) of nicotinamide, which is also supplemented through nutrition as a vitamin (also known as vitamin B3).This deficiency is most problematic during times of illness or stress. Precipitating factors that may cause acute episodes of Hartnup disease may include a period of poor nutrition, fever, exposure to sunlight, sulphonamide medications, illness, and/or psychological stress. | Causes of Hartnup Disease. Hartnup disease is caused by alterations (mutations) in the SLC6A19 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.These alterations are inherited in an autosomal recessive manner. Most genetic diseases are determined by the status of the two copies of a gene, 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.The SLC6A19 gene produces a protein known as an amino acid transporter, which serves to assist the movement (or transport) of specific amino acids within the body. This protein is especially active within the kidneys and the intestines, although these organs are otherwise unaffected and function normally. The amino acids affected include tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine, and valine.Amino acids are the chemical building blocks of proteins and are essential for proper growth and development. Because of the underlying genetic defect in Hartnup disease, the intestines cannot properly absorb amino acids and the kidney cannot properly reabsorb them, leading to excessive amounts of amino acids being lost through the passage of urine. This leaves the body with reduced amounts of amino acids to serve as the building blocks of proteins. Deficiency of the amino acid tryptophan is believed to account for the symptoms associated with Hartnup disease. Tryptophan is essential for the creation (synthesis) of nicotinamide, which is also supplemented through nutrition as a vitamin (also known as vitamin B3).This deficiency is most problematic during times of illness or stress. Precipitating factors that may cause acute episodes of Hartnup disease may include a period of poor nutrition, fever, exposure to sunlight, sulphonamide medications, illness, and/or psychological stress. | 554 | Hartnup Disease |
nord_554_3 | Affects of Hartnup Disease | Hartnup disease affects both males and females in equal numbers. The disorder usually begins in childhood and continues into adulthood. The number of people affected by Hartnup disease is unknown. It has been estimated to occur at a frequency of approximately one in 30,000 individuals based upon newborn screening results in the United States and Australia. | Affects of Hartnup Disease. Hartnup disease affects both males and females in equal numbers. The disorder usually begins in childhood and continues into adulthood. The number of people affected by Hartnup disease is unknown. It has been estimated to occur at a frequency of approximately one in 30,000 individuals based upon newborn screening results in the United States and Australia. | 554 | Hartnup Disease |
nord_554_4 | Related disorders of Hartnup Disease | Symptoms of the following disorders can be similar to those of Hartnup disease. Comparisons may be useful for a differential diagnosis:Pellagra is an illness that results from a deficiency of nicotinic acid and occasionally tryptophan. This disorder is characterized by lack of appetite, weakness, discomfort, emotional instability, insomnia, bouts of diarrhea or constipation, a burning or stinging sensation of the skin (especially following exposure to the sun), and a sore mouth. The skin may become reddish-brown, scaly, and rough. This disorder usually occurs from deficiencies in the diet such as those that occur in countries where corn or maize is the staple food. It is very rare in the United States.In addition to pellagra, the skin rash associated with Hartnup disease can be similar to the malar rash seen in lupus, infantile atopic dermatitis, seborrheic dermatitis, carcinoid syndrome, xeroderma pigmentosum, and a variety of other metabolic disorders including phenylketonuria and blue diaper syndrome. The neurological symptoms of Hartnup disease can resemble those seen in other metabolic disorders and ataxia-telangiectasia and other forms of ataxia. | Related disorders of Hartnup Disease. Symptoms of the following disorders can be similar to those of Hartnup disease. Comparisons may be useful for a differential diagnosis:Pellagra is an illness that results from a deficiency of nicotinic acid and occasionally tryptophan. This disorder is characterized by lack of appetite, weakness, discomfort, emotional instability, insomnia, bouts of diarrhea or constipation, a burning or stinging sensation of the skin (especially following exposure to the sun), and a sore mouth. The skin may become reddish-brown, scaly, and rough. This disorder usually occurs from deficiencies in the diet such as those that occur in countries where corn or maize is the staple food. It is very rare in the United States.In addition to pellagra, the skin rash associated with Hartnup disease can be similar to the malar rash seen in lupus, infantile atopic dermatitis, seborrheic dermatitis, carcinoid syndrome, xeroderma pigmentosum, and a variety of other metabolic disorders including phenylketonuria and blue diaper syndrome. The neurological symptoms of Hartnup disease can resemble those seen in other metabolic disorders and ataxia-telangiectasia and other forms of ataxia. | 554 | Hartnup Disease |
nord_554_5 | Diagnosis of Hartnup Disease | Due to the variability of symptoms, unambiguous diagnosis can only be made through urine analysis. Pediatricians can request this analysis from selected pathology centers. The test is based on the detection of elevated amino acids in the urine by chromatography and mass spectroscopy.Molecular genetic testing can confirm a diagnosis of Hartnup disease in some cases. Molecular genetic testing can detect genetic alterations in the SLC19A6 gene known to cause the disorder, but usually is not necessary to obtain a diagnosis. | Diagnosis of Hartnup Disease. Due to the variability of symptoms, unambiguous diagnosis can only be made through urine analysis. Pediatricians can request this analysis from selected pathology centers. The test is based on the detection of elevated amino acids in the urine by chromatography and mass spectroscopy.Molecular genetic testing can confirm a diagnosis of Hartnup disease in some cases. Molecular genetic testing can detect genetic alterations in the SLC19A6 gene known to cause the disorder, but usually is not necessary to obtain a diagnosis. | 554 | Hartnup Disease |
nord_554_6 | Therapies of Hartnup Disease | Treatment
Individuals with Hartnup disease who do not develop symptoms will usually not require any treatment. Low protein diets (vegan or similar) may trigger symptomatic episodes, which can be reduced or avoided by maintaining good nutrition including a high protein diet, avoiding excess exposure the sun, and avoiding certain drugs such as sulphonamide drugs. Supplementing the diet with nicotinamide or niacin is also of benefit in preventing Hartnup disease episodes.In some instances, during a symptomatic episode, treatment with nicotinamide may be recommended.According to the medical literature, at least one individual showed an improvement of symptoms after treatment with the compound L-tryptophan ethyl ester, which restored tryptophan levels in both the serum and cerebrospinal fluid.Other treatment is symptomatic and supportive. Genetic counseling may be helpful for affected families. | Therapies of Hartnup Disease. Treatment
Individuals with Hartnup disease who do not develop symptoms will usually not require any treatment. Low protein diets (vegan or similar) may trigger symptomatic episodes, which can be reduced or avoided by maintaining good nutrition including a high protein diet, avoiding excess exposure the sun, and avoiding certain drugs such as sulphonamide drugs. Supplementing the diet with nicotinamide or niacin is also of benefit in preventing Hartnup disease episodes.In some instances, during a symptomatic episode, treatment with nicotinamide may be recommended.According to the medical literature, at least one individual showed an improvement of symptoms after treatment with the compound L-tryptophan ethyl ester, which restored tryptophan levels in both the serum and cerebrospinal fluid.Other treatment is symptomatic and supportive. Genetic counseling may be helpful for affected families. | 554 | Hartnup Disease |
nord_555_0 | Overview of Hashimoto Encephalopathy | Hashimoto encephalopathy is a rare disorder characterized by impaired brain function (encephalopathy). The exact cause is unknown, but it is believed to be an immune-mediated disorder or a disorder in which there is inflammation resulting from abnormal functioning of the immune system. Affected individuals have the presence of antithyroid antibodies in their body. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Antithyroid antibodies are ones that mistakenly target thyroid tissue. However, it is unclear whether these antibodies play any role in the development of Hashimoto encephalopathy or are a coincidental finding. The main signs and symptoms are related to the encephalopathy. The onset of impaired brain function is rapid (acute), while other times it can develop slowly over many years. The specific symptoms, severity, and course of the disorder can vary greatly among affected individuals. The disorder often responds to therapy with corticosteroids.Some researchers believe there is a relationship between Hashimoto encephalopathy and Hashimoto thyroiditis, an autoimmune disorder in which antithyroid antibodies mistakenly damage the thyroid. The name Hashimoto encephalopathy comes from the presence of antithyroid antibodies and encephalopathy occurring together. Whether these two disorders are linked in any way is not fully understood. Because there is no evidence that the antithyroid antibodies in Hashimoto encephalopathy contribute to brain damage, and because most of the affected individuals have a normal-functioning thyroid, some researchers believe these are coincidental findings. Some physicians have preferred the name steroid-responsive encephalopathy associated with autoimmune thyroiditis or SREAT instead of Hashimoto encephalopathy. | Overview of Hashimoto Encephalopathy. Hashimoto encephalopathy is a rare disorder characterized by impaired brain function (encephalopathy). The exact cause is unknown, but it is believed to be an immune-mediated disorder or a disorder in which there is inflammation resulting from abnormal functioning of the immune system. Affected individuals have the presence of antithyroid antibodies in their body. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Antithyroid antibodies are ones that mistakenly target thyroid tissue. However, it is unclear whether these antibodies play any role in the development of Hashimoto encephalopathy or are a coincidental finding. The main signs and symptoms are related to the encephalopathy. The onset of impaired brain function is rapid (acute), while other times it can develop slowly over many years. The specific symptoms, severity, and course of the disorder can vary greatly among affected individuals. The disorder often responds to therapy with corticosteroids.Some researchers believe there is a relationship between Hashimoto encephalopathy and Hashimoto thyroiditis, an autoimmune disorder in which antithyroid antibodies mistakenly damage the thyroid. The name Hashimoto encephalopathy comes from the presence of antithyroid antibodies and encephalopathy occurring together. Whether these two disorders are linked in any way is not fully understood. Because there is no evidence that the antithyroid antibodies in Hashimoto encephalopathy contribute to brain damage, and because most of the affected individuals have a normal-functioning thyroid, some researchers believe these are coincidental findings. Some physicians have preferred the name steroid-responsive encephalopathy associated with autoimmune thyroiditis or SREAT instead of Hashimoto encephalopathy. | 555 | Hashimoto Encephalopathy |
nord_555_1 | Symptoms of Hashimoto Encephalopathy | The most important symptom is impaired brain function (encephalopathy), namely, altered mental status. It is impairment of the cognition, attention, orientation, sleep-wake cycle and consciousness.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 cases, 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. Affected individuals and families should talk to their physicians and medical team about their specific case, associated symptoms and overall prognosis.The specific symptoms and severity of the disorder can vary greatly from one individuals to another. The disorder may follow a relapsing and remitting course, which means that symptoms of cognitive decline and altered consciousness go through cycles where they worsen and improve. In some individuals, the disorder will be slowly progressive rather than relapsing and remitting. In these individuals, there is a progressive pattern of cognitive decline including confusion, hallucinations, dementia, and, impairment of the sleep-wake cycle including difficulty in maintaining sleep and sleeping for longer periods of time than usual. Depression may be the initial sign in this form. Although there are two distinct patterns of disease development for Hashimoto encephalopathy, the specific signs and symptoms can overlap. The severity, progression and specific symptoms associated with the disorder can vary greatly from one person to another. Additional symptoms that can develop include seizures, fatigue, jitteriness or nervousness, overresponsive reflexes (hyperreflexia), poor appetite, confusion, loss of blood flow to an area of the brain called the cerebrum (cerebral ischemia), altered consciousness, and loss of contact with reality (psychosis). Sometimes, individuals may develop tremors, abnormal jerky movements (myoclonus), poor coordination of voluntary movements (ataxia), and slurred speech (dysarthria). Affected individuals may be inattentive, lack concentration, and fail to understand basic concepts. They can also exhibit behavioral changes including depression, anxiety, emotional instability, social withdrawal, and changes in their personality. The disorder can follow a limited course that resolves without treatment (self-limited), follow a course where the disease becomes worse over time (progressive), or follow a relapsing and remitting course. Many people with Hashimoto encephalopathy have a normal-functioning thyroid (euthyroid) despite the presence of antithyroid antibodies. Other individuals may have an underactive thyroid (hypothyroidism) or overactive thyroid (hyperthyroidism). The thyroid is part of the endocrine system, the network of glands that secrete hormones that regulate that chemical processes (metabolism) that influence the body’s heart rate, body temperature and blood pressure. | Symptoms of Hashimoto Encephalopathy. The most important symptom is impaired brain function (encephalopathy), namely, altered mental status. It is impairment of the cognition, attention, orientation, sleep-wake cycle and consciousness.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 cases, 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. Affected individuals and families should talk to their physicians and medical team about their specific case, associated symptoms and overall prognosis.The specific symptoms and severity of the disorder can vary greatly from one individuals to another. The disorder may follow a relapsing and remitting course, which means that symptoms of cognitive decline and altered consciousness go through cycles where they worsen and improve. In some individuals, the disorder will be slowly progressive rather than relapsing and remitting. In these individuals, there is a progressive pattern of cognitive decline including confusion, hallucinations, dementia, and, impairment of the sleep-wake cycle including difficulty in maintaining sleep and sleeping for longer periods of time than usual. Depression may be the initial sign in this form. Although there are two distinct patterns of disease development for Hashimoto encephalopathy, the specific signs and symptoms can overlap. The severity, progression and specific symptoms associated with the disorder can vary greatly from one person to another. Additional symptoms that can develop include seizures, fatigue, jitteriness or nervousness, overresponsive reflexes (hyperreflexia), poor appetite, confusion, loss of blood flow to an area of the brain called the cerebrum (cerebral ischemia), altered consciousness, and loss of contact with reality (psychosis). Sometimes, individuals may develop tremors, abnormal jerky movements (myoclonus), poor coordination of voluntary movements (ataxia), and slurred speech (dysarthria). Affected individuals may be inattentive, lack concentration, and fail to understand basic concepts. They can also exhibit behavioral changes including depression, anxiety, emotional instability, social withdrawal, and changes in their personality. The disorder can follow a limited course that resolves without treatment (self-limited), follow a course where the disease becomes worse over time (progressive), or follow a relapsing and remitting course. Many people with Hashimoto encephalopathy have a normal-functioning thyroid (euthyroid) despite the presence of antithyroid antibodies. Other individuals may have an underactive thyroid (hypothyroidism) or overactive thyroid (hyperthyroidism). The thyroid is part of the endocrine system, the network of glands that secrete hormones that regulate that chemical processes (metabolism) that influence the body’s heart rate, body temperature and blood pressure. | 555 | Hashimoto Encephalopathy |
nord_555_2 | Causes of Hashimoto Encephalopathy | The exact cause of Hashimoto encephalopathy is unknown. However, some clinical researchers believe that the disorder is most likely the result of an abnormal immune system response to an infection or other trigger. Many researchers suggest that the disorder may represent, in part, an abnormal immune reaction directed against the body’s own tissues (autoimmune disorder). In autoimmune disorders, the body’s natural defenses (e.g. antibodies, lymphocytes) against substances that are perceived as foreign (antigens) inappropriately begin to attack healthy tissues for unknown reasons. When antibodies mistakenly target healthy tissue, they may be referred to as autoantibodies. Individuals with Hashimoto encephalopathy have varying levels of antithyroid antibodies. The presence of antithyroid antibodies means that a person’s immune system is not functioning properly. However, despite the presence of these antibodies, there has been no evidence to confirm that they play a role in the brain damage that characterizes this disorder. Also, the specific levels of antithyroid antibodies in the body does not correlate with the severity of the neurological symptoms. Researchers have discovered the presence of anti-alpha enolase antibodies. Alpha enolase is an enzyme expressed in most tissues of the body. The presence of two autoantibodies, anti-alpha enolase and antithyroid antibodies, supports the theory that there is an active autoimmune process affecting individuals with Hashimoto encephalopathy. Some researchers speculate that the autoimmune process may involve inflammation and damage to blood vessels within the brain (autoimmune cerebral vasculitis). However, more research is necessary to determine the exact, underlying mechanisms that cause Hashimoto encephalopathy. | Causes of Hashimoto Encephalopathy. The exact cause of Hashimoto encephalopathy is unknown. However, some clinical researchers believe that the disorder is most likely the result of an abnormal immune system response to an infection or other trigger. Many researchers suggest that the disorder may represent, in part, an abnormal immune reaction directed against the body’s own tissues (autoimmune disorder). In autoimmune disorders, the body’s natural defenses (e.g. antibodies, lymphocytes) against substances that are perceived as foreign (antigens) inappropriately begin to attack healthy tissues for unknown reasons. When antibodies mistakenly target healthy tissue, they may be referred to as autoantibodies. Individuals with Hashimoto encephalopathy have varying levels of antithyroid antibodies. The presence of antithyroid antibodies means that a person’s immune system is not functioning properly. However, despite the presence of these antibodies, there has been no evidence to confirm that they play a role in the brain damage that characterizes this disorder. Also, the specific levels of antithyroid antibodies in the body does not correlate with the severity of the neurological symptoms. Researchers have discovered the presence of anti-alpha enolase antibodies. Alpha enolase is an enzyme expressed in most tissues of the body. The presence of two autoantibodies, anti-alpha enolase and antithyroid antibodies, supports the theory that there is an active autoimmune process affecting individuals with Hashimoto encephalopathy. Some researchers speculate that the autoimmune process may involve inflammation and damage to blood vessels within the brain (autoimmune cerebral vasculitis). However, more research is necessary to determine the exact, underlying mechanisms that cause Hashimoto encephalopathy. | 555 | Hashimoto Encephalopathy |
nord_555_3 | Affects of Hashimoto Encephalopathy | Hashimoto encephalopathy is a rare disease that affects women more often than men. The disorder is estimated to affect 2.1 per 100,000 individuals in the general population. It can affect children, but only approximately 60 affected children have been described in the medical literature. Rare disorders often go misdiagnosed or undiagnosed making it difficult to determine the true frequency in the general population. | Affects of Hashimoto Encephalopathy. Hashimoto encephalopathy is a rare disease that affects women more often than men. The disorder is estimated to affect 2.1 per 100,000 individuals in the general population. It can affect children, but only approximately 60 affected children have been described in the medical literature. Rare disorders often go misdiagnosed or undiagnosed making it difficult to determine the true frequency in the general population. | 555 | Hashimoto Encephalopathy |
nord_555_4 | Related disorders of Hashimoto Encephalopathy | Symptoms of the following disorders can be similar to those of Hashimoto encephalopathy. Comparisons may be useful for a differential diagnosis.Acute disseminated encephalomyelitis (ADEM) is a neurological, immune-mediated disorder in which widespread inflammation of the brain and spinal cord damages tissue known as white matter. White matter is tissue composed of nerve fibers, many of which are covered by a collection of fats and proteins known as myelin. Myelin, which collectively may be referred to as the myelin sheath, protects the nerve fibers, acts as an insulator and increases the speed of transmission of nerve signals. Damage to the myelin sheath (demyelination) affects the nerve’s ability to transmit information and potentially can cause a wide range of neurological symptoms. The specific symptoms and severity can vary from one individual to another. In some individuals, ADEM is preceded by a viral infection or vaccination. The exact cause the disorder is unknown although it is believed that an improper response of the immune system plays a role its development. ADEM must be differentiated from other demyelinating disorders such as multiple sclerosis. (For more information on this disorder, choose “acute disseminated encephalomyelitis” as your search term in the Rare Disease Database.) Alzheimer’s disease is a progressive condition of the brain that affects memory, thought, and language. The degenerative changes of Alzheimer’s disease lead to patches or plaques in the brain and the entanglement of nerve fibers (neurofibrillary tangles). Memory loss and behavioral changes occur as a result of these changes in brain tissue. Alzheimer’s disease is usually a slow progressive illness that occurs in midlife but becomes increasingly more common over the age of 65 years, in contrast to the frontotemporal degenerations. Difficulty with short-term memory is usually the first symptom and early behavioral changes may not be noticed. As the disease progresses, memory loss increases and there are changes in personality, mood and behavior. Disturbances of judgment and concentration occur, along with confusion and restlessness. The type, severity, sequence, and progression of mental changes vary widely. Long periods with little change are common, although occasionally the disease can be rapidly progressive. (For more information on this disorder, choose “Alzheimer” as your search term in the Rare Disease Database.)Encephalopathy is a general term for disease, damage, or malfunction of the brain. There are many different causes of encephalopathy, including toxic, genetic, metabolic, and infectious disorders. Disorders commonly excluded in the differential diagnosis of Hashimoto encephalopathy include Creutzfeldt-Jakob disease, paraneoplastic syndromes, nonvasculitic autoimmune inflammatory meningoencephalitis, and progressive dementias. Affected individuals may often be misdiagnosed with a psychiatric condition. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | Related disorders of Hashimoto Encephalopathy. Symptoms of the following disorders can be similar to those of Hashimoto encephalopathy. Comparisons may be useful for a differential diagnosis.Acute disseminated encephalomyelitis (ADEM) is a neurological, immune-mediated disorder in which widespread inflammation of the brain and spinal cord damages tissue known as white matter. White matter is tissue composed of nerve fibers, many of which are covered by a collection of fats and proteins known as myelin. Myelin, which collectively may be referred to as the myelin sheath, protects the nerve fibers, acts as an insulator and increases the speed of transmission of nerve signals. Damage to the myelin sheath (demyelination) affects the nerve’s ability to transmit information and potentially can cause a wide range of neurological symptoms. The specific symptoms and severity can vary from one individual to another. In some individuals, ADEM is preceded by a viral infection or vaccination. The exact cause the disorder is unknown although it is believed that an improper response of the immune system plays a role its development. ADEM must be differentiated from other demyelinating disorders such as multiple sclerosis. (For more information on this disorder, choose “acute disseminated encephalomyelitis” as your search term in the Rare Disease Database.) Alzheimer’s disease is a progressive condition of the brain that affects memory, thought, and language. The degenerative changes of Alzheimer’s disease lead to patches or plaques in the brain and the entanglement of nerve fibers (neurofibrillary tangles). Memory loss and behavioral changes occur as a result of these changes in brain tissue. Alzheimer’s disease is usually a slow progressive illness that occurs in midlife but becomes increasingly more common over the age of 65 years, in contrast to the frontotemporal degenerations. Difficulty with short-term memory is usually the first symptom and early behavioral changes may not be noticed. As the disease progresses, memory loss increases and there are changes in personality, mood and behavior. Disturbances of judgment and concentration occur, along with confusion and restlessness. The type, severity, sequence, and progression of mental changes vary widely. Long periods with little change are common, although occasionally the disease can be rapidly progressive. (For more information on this disorder, choose “Alzheimer” as your search term in the Rare Disease Database.)Encephalopathy is a general term for disease, damage, or malfunction of the brain. There are many different causes of encephalopathy, including toxic, genetic, metabolic, and infectious disorders. Disorders commonly excluded in the differential diagnosis of Hashimoto encephalopathy include Creutzfeldt-Jakob disease, paraneoplastic syndromes, nonvasculitic autoimmune inflammatory meningoencephalitis, and progressive dementias. Affected individuals may often be misdiagnosed with a psychiatric condition. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.) | 555 | Hashimoto Encephalopathy |
nord_555_5 | Diagnosis of Hashimoto Encephalopathy | A diagnosis of Hashimoto encephalopathy is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. By definition, Hashimoto encephalopathy must have detectable levels of antithyroid antibodies in the body. However, there is no correlation between the amount of antibody levels and the presence or severity of symptoms. Antithyroid antibodies are relatively common in the general population, so this finding must occur in individuals with the characteristic findings associated with Hashimoto encephalopathy and in whom other potential diagnoses have been ruled out. Clinical Testing and Workup
Blood tests may reveal high levels of antithyroid antibodies. Cerebrospinal fluid, which is the clear fluid that supports and protects the brain and spinal cord, may be studied, which may show nonspecific findings including abnormally high levels of certain proteins.Physicians may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and slowing of background activity. An EEG can also be used to help to detect seizures. Specialized imaging techniques may be performed including magnetic resonance imaging (MRI). An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. An MRI is usually normal, and is used to exclude other causes of encephalopathy. In uncommon instances can show widespread (diffuse) or specific (focal) changes in white matter. | Diagnosis of Hashimoto Encephalopathy. A diagnosis of Hashimoto encephalopathy is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. By definition, Hashimoto encephalopathy must have detectable levels of antithyroid antibodies in the body. However, there is no correlation between the amount of antibody levels and the presence or severity of symptoms. Antithyroid antibodies are relatively common in the general population, so this finding must occur in individuals with the characteristic findings associated with Hashimoto encephalopathy and in whom other potential diagnoses have been ruled out. Clinical Testing and Workup
Blood tests may reveal high levels of antithyroid antibodies. Cerebrospinal fluid, which is the clear fluid that supports and protects the brain and spinal cord, may be studied, which may show nonspecific findings including abnormally high levels of certain proteins.Physicians may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and slowing of background activity. An EEG can also be used to help to detect seizures. Specialized imaging techniques may be performed including magnetic resonance imaging (MRI). An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues, including the brain. An MRI is usually normal, and is used to exclude other causes of encephalopathy. In uncommon instances can show widespread (diffuse) or specific (focal) changes in white matter. | 555 | Hashimoto Encephalopathy |
nord_555_6 | Therapies of Hashimoto Encephalopathy | Treatment
Hashimoto encephalopathy is treated with medications known as corticosteroids. Corticosteroids are used to treat inflammation and affected individuals have responded very well to this treatment. The best dose (optimal dose) is unknown, but will vary based on several factors including a person’s age, overall health, and individual tolerance of the medication. Treatment usually begins with high doses of corticosteroids, which are then slowly lowered (tapered off). Long-term therapy with high-doses of corticosteroids is associated with significant side effects, so the high doses are initially used to bring the disorder under control before the doses are lowered. In most individuals, symptoms usually improve or go away completely within a few months although people required treatment for as long as two years. If corticosteroids are ineffective or cannot be tolerated by an individual, other medications specifically mediations that suppress the activity of the immune system (immunosuppression) have been tried including azathioprine and cyclophosphamide. In patients who do not fully respond to the corticosteroid therapy, other therapeutic options such intravenous immune globulin (IVIG) or plasmapheresis could be considered. The mechanism of IVIG is associated with neutralizing circulatory autoantibodies. Plasmapheresis can remove autoantibodies of the blood. Plasmapheresis is a method for removing unwanted substances (toxins, metabolic substances, autoantibodies) from the blood. During plasmapheresis, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma and the blood is transfused back into the affected individual. Some individuals may relapse and require another course of corticosteroid therapy, or immunosuppressive therapy.Sometimes, anti-seizure (anti-convulsants) medications may be necessary to treat seizures and antipsychotic medication for the patients who are suffering from psychiatric symptoms or delirium. | Therapies of Hashimoto Encephalopathy. Treatment
Hashimoto encephalopathy is treated with medications known as corticosteroids. Corticosteroids are used to treat inflammation and affected individuals have responded very well to this treatment. The best dose (optimal dose) is unknown, but will vary based on several factors including a person’s age, overall health, and individual tolerance of the medication. Treatment usually begins with high doses of corticosteroids, which are then slowly lowered (tapered off). Long-term therapy with high-doses of corticosteroids is associated with significant side effects, so the high doses are initially used to bring the disorder under control before the doses are lowered. In most individuals, symptoms usually improve or go away completely within a few months although people required treatment for as long as two years. If corticosteroids are ineffective or cannot be tolerated by an individual, other medications specifically mediations that suppress the activity of the immune system (immunosuppression) have been tried including azathioprine and cyclophosphamide. In patients who do not fully respond to the corticosteroid therapy, other therapeutic options such intravenous immune globulin (IVIG) or plasmapheresis could be considered. The mechanism of IVIG is associated with neutralizing circulatory autoantibodies. Plasmapheresis can remove autoantibodies of the blood. Plasmapheresis is a method for removing unwanted substances (toxins, metabolic substances, autoantibodies) from the blood. During plasmapheresis, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma and the blood is transfused back into the affected individual. Some individuals may relapse and require another course of corticosteroid therapy, or immunosuppressive therapy.Sometimes, anti-seizure (anti-convulsants) medications may be necessary to treat seizures and antipsychotic medication for the patients who are suffering from psychiatric symptoms or delirium. | 555 | Hashimoto Encephalopathy |
nord_556_0 | Overview of Heavy Metal Poisoning | Heavy metal poisoning is the accumulation of heavy metals, in toxic amounts, in the soft tissues of the body. Symptoms and physical findings associated with heavy metal poisoning vary according to the metal accumulated. Many of the heavy metals, such as zinc, copper, chromium, iron and manganese, are essential to body function in very small amounts. But, if these metals accumulate in the body in concentrations sufficient to cause poisoning, then serious damage may occur. The heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmium. Heavy metal poisoning may occur as a result of industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints. | Overview of Heavy Metal Poisoning. Heavy metal poisoning is the accumulation of heavy metals, in toxic amounts, in the soft tissues of the body. Symptoms and physical findings associated with heavy metal poisoning vary according to the metal accumulated. Many of the heavy metals, such as zinc, copper, chromium, iron and manganese, are essential to body function in very small amounts. But, if these metals accumulate in the body in concentrations sufficient to cause poisoning, then serious damage may occur. The heavy metals most commonly associated with poisoning of humans are lead, mercury, arsenic and cadmium. Heavy metal poisoning may occur as a result of industrial exposure, air or water pollution, foods, medicines, improperly coated food containers, or the ingestion of lead-based paints. | 556 | Heavy Metal Poisoning |
nord_556_1 | Symptoms of Heavy Metal Poisoning | The symptoms of heavy metal poisoning vary according to which type of metal overexposure is involved. Some specific examples are:ARSENIC POISONINGArsenic is used in the manufacture of pesticides. The gas from arsenic also has some industrial uses. Overexposure may cause headaches, drowsiness, confusion, seizures, and life-threatening complications. Neurological symptoms include brain damage (encephalopathy), nerve disease of the extremities (peripheral neuropathy), pericapillary hemorrhages within the white matter, and loss or deficiency of the fatty coverings (myelin) around these nerve fibers (demyelination). Skin problems include transverse white bands on the fingernails (mees' lines) and excessive accumulation of fluid in the soft layers of tissue below the skin (edema). Gastrointestinal symptoms include a flu-like illness (gastroenteritis) that is characterized by vomiting; abdominal pain; fever; and diarrhea, which, in some cases, may be bloody. Other symptoms include breakdown of the hemoglobin of red blood cells (hemolysis), a low level of iron in the red blood cells (anemia), and low blood pressure (hypotension). Some individuals may experience a garlic-like odor that may be detectable on the breath.In cases of chronic poisoning, weakness, muscle aches, chills, and fever may develop. The onset of symptoms in chronic arsenic poisoning is about two to eight weeks after exposure. Skin and nail symptoms include hardened patches of skin (hyperkeratosis) with unusually deep creases on the palms of the hands and the soles of the feet, unusual darkening of certain areas of the skin (hyperpigmentation), transverse white bands on the fingernails (mees' lines), and a scale like inflammation of the skin (exfoliative dermatitis). Other symptoms include inflammation of sensory and motor nerves (polyneuritis) and the mucose membrane lining the throat.Inorganic arsenic accumulates in the liver, spleen, kidneys, lungs, and gastrointestinal tract. It then passes through these sites but leaves a residue in tissues such as skin, hair, and nails. Symptoms of acute inorganic arsenic poisoning include severe burning of the mouth and throat, abdominal pain, nausea, vomiting, diarrhea, low blood pressure (hypotension), and muscle spasms. Individuals with severe inorganic arsenic poisoning may experience heart problems (cardiomyopathy); accumulation of acid in the tubes of the kidneys (renal tubular acidosis); breakdown of the hemoglobin of red blood cells (hemolysis); irregular heart rhythms (ventricular arrhythmias); coma; seizures; bleeding within the intestines (intestinal hemorrhage); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).CADMIUM POISONINGCadmium is used for many items, including electroplating, storage batteries, vapor lamps and in some solders. The onset of symptoms may be delayed for two to four hours after exposure. Overexposure may cause fatigue, headaches, nausea, vomiting, abdominal cramps, diarrhea, and fever. In addition, progressive loss of lung function (emphysema), abnormal buildup of fluid within the lungs (pulmonary edema), and breathlessness (dyspnea) may also be present. In some cases, affected individuals may exhibit increased salivation; yellowing of the teeth; an unusually rapid heart beat (tachycardia); low levels of iron within the red blood cells (anemia); bluish discoloration (cyanosis) of the skin and mucous membranes due to insufficient oxygen supply to these tissues; and/or an impaired sense of smell (anosmia). Individuals with cadmium poisoning may also experience improper functioning of the canals with the kidney (renal tubular dysfunction) characterized by excretion of abnormally high levels of protein in the urine (proteinuria), minor changes in liver function, and/or softening of certain bones (osteomalacia).CHROMIUM POISONINGChromium is used in the manufacture of cars, glass, pottery and linoleum. Exposure to too much chromium may cause lung and respiratory tract cancer as well as kidney diseases. In addition, overexposure to chromium may also cause gastrointestinal symptoms, such as diarrhea and vomiting, often with blood. Symptoms may lead to severe water-electrolyte disorders, increased mild acidity of blood and body tissues (acidosis), and/or inadequate blood flow to its tissues resulting in shock. Lesions on the kidneys, liver, and muscular layer of the heart (myocardium) may also develop.COBALT POISONINGCobalt, used in making jet engines, may cause nausea, vomiting, lack of appetite (anorexia), ear ringing (tinnitus), nerve damage, respiratory diseases, an unusually large thyroid gland (goiter), and/or heart and/or kidney damage.LEAD POISONINGLead production workers, battery plant workers, welders and solders may be overexposed to lead if proper precautions are not taken. Lead is stored in the bone but may affect any organ system. The effects of lead poisoning varies depending on the age of the individual and the amount of exposure.In children, symptoms vary depending upon the degree of exposure to lead. Some affected individuals may not have any noticeable symptoms. Symptoms usually develop over a three to six week time period. Lead overexposure may cause children to be less playful, clumsier, irritable, and sluggish (lethargic). In some cases, symptoms include headaches, vomiting, abdominal pain, lack of appetite (anorexia), constipation, slurred speech (dysarthria), changes in kidney function, unusually high amounts of protein in the blood (hyperproteinemia), and unusually pale skin (pallor) resulting from a low level of iron in the red blood cells (anemia). Neurological symptoms associated with lead overexposure include an impaired ability to coordinate voluntary movements (ataxia), brain damage (encephalopathy), seizures, convulsions, swelling of the optic nerve (papilledema), and/or impaired consciousness. Some affected children experience learning or behavioral problems such as mental retardation and selective deficits in language, cognitive function, balance, behavior, and school performance. In some cases, symptoms may be life-threatening.In adults, overexposure to lead may cause high blood pressure and damage to the reproductive organs. Additional symptoms may include fever, headaches, fatigue, sluggishness (letheragy), vomiting, loss of appetite (anorexia), abdominal pain, constipation, joint pain, loss of recently acquired skills, incoordination, listlessness, difficulty sleeping (insomnia), irritability, altered consciousness, hallucinations, and/or seizures. In addition, affected individuals may experience low levels of iron in the red blood cells (anemia), peripheral neuropathy, and, in some cases, brain damage (encephalopathy). Some affected individuals experience decreased muscle strength and endurance; kidney disease; wrist drop; and behavioral changes such as hostility, depression, and/or anxiety. In some cases, symptoms may be life-threatening.Lead is excreted in urine and feces. However, it may also appear in hair, nails, sweat, saliva, and breast milk.MANGANESE POISONINGManganese is used as a purifying agent in the production of several metals. Symptoms associated with overexposure to manganese may include damage to the central nervous system and pneumonia. Additional symptoms and physical findings include weakness, fatigue, confusion, hallucinations, odd or awkward manner of walking (gait), muscle spasms (dystonia), rigidity of the trunk, stiffness, awkwardness of the limbs, tremors of the hands, and psychiatric abnormalities.MERCURY POISONINGMercury is used by dental assistants and hygienists, and chemical workers. Mercury can affect the lungs, kidneys, brain, and/or skin. Symptoms of mercury poisoning include fatigue, depression, sluggishness (letheragy), irritability, and headaches.Respiratory symptoms associated with inhalation to mercury vapors include coughing, breathlessness (dyspnea), tightness or burning pain in the chest, and/or respiratory distress. Some affected individuals may experience abnormal buildup of fluid in the lungs (pulmonary edema); pneumonia; and/or abnormal formation of fibrous tissue (fibrosis).There may be behavioral and neurological changes associated with overexposure to mercury poisoning, such as excitability and quick-tempered behavior, lack of concentration, and loss of memory. Shock and permanent brain damage may also be result from mercury poisoning. Some affected individuals experience mental confusion. A progressive cerebellar syndrome with impaired ability to coordinate voluntary movements (ataxia) of the arms may also be present. Abnormal involuntary movements of the body such as uncontrolled jerky movements combined with slow, writhing movements (choreoathetosis) are common. Additional symptoms include non-inflammatory degenerative disease of the nerves (polyneuropathy); impaired ability to coordinate voluntary movements (cerebellar ataxia); tremors of the legs and arms and, in some cases, of the tongue and lips; seizures; and/or slurred speech (dysarthria). Changes in mood, behavior, and consciousness may also occur.In some cases of chronic exposure to inorganic mercury a personality disorder known as erethism or mad hatter syndrome may occur. Symptoms associated with mad hatter syndrome include memory loss, excessive shyness, abnormal excitability, and/or insomnia. This syndrome was described in workers with occupational exposure to mercury in the felt-hat industry.Many affected individual experience sensory impairments such as visual problems (e.g. constriction of visual fields, tunnel vision, and blindness) as well as hearing loss.Some individuals may experience skin changes such as painful swelling and pink coloration of the fingers and toes (acrodynia); persistent redness or inflammation of the skin (erythema); extreme sensitivity (hyperesthesia) of the affected areas; and tingling and sensory disturbances.In some cases, other affected individuals may experience stomach and intestinal disturbances; kidney damage; dehydration; acute renal failure; inflammation of the gums (gingivitis); severe local irritation of the mouth and pharynx, accompanied by vomiting; and/or abdominal cramps with bloody diarrhea.Mercury is mainly excreted through the urine and feces.PHOSPHORUS POISONINGSymptoms associated with phosphorus poisoning include weakness, headaches, vomiting, sweating, abdominal cramps, salivation, wheezing secondary to bronchial spasm, drooping of the upper eyelids (ptosis), contraction of the pupil (miosis), and/or muscular weakness and twitching. In addition, non-inflammatory degenerative disease of the sensorimotor nerves (sensorimotor polyneuropathy) may advance to progressive deterioration (atrophy). In some cases, respiratory paralysis may also occur.THALLIUM POISONINGSymptoms associated with thallium poisoning include extreme drowsiness (somnolence), nausea, vomiting, abdominal pain, and bloody vomiting (hematemesis). Some affected individuals may experience the loss of most or all of their scalp hair (alopecia); rapidly progressive and painful sensory polyneuropathy; motor neuropathy; cranial nerve palsies; seizures; impaired ability to coordinate voluntary movements (cerebellar ataxia); and/or mental retardation. Some individuals may experience eye symptoms including wasting away (atrophy) of the optic nerve (optic atrophy), inflammation of the optic nerve (retrobulbar neuritis), and impaired functioning of the muscles of the eyes (ophthalmoplegia). In some cases, thallium poisoning may progress to include renal and cardiac failure, confusion, psychosis, organic brain syndrome, and/or coma.ADDITIONAL METAL POISONINGSAdditional metals that may cause poisoning include antimony, aluminum, barium, bismuth, copper, gold, iron, lithium, platinum, silver, tin, and zinc. Common symptoms of poisoning from these metals may include gastrointestinal, renal, and neurological symptoms, such as headaches, irritability, psychosis, stupor, coma, and convulsions.Antimony is used for hardening lead, and in the manufacture of batteries and cables. It may possibly cause lung disease and skin cancer, especially in those who smoke.Copper is used in the manufacture of electrical wires. It may cause a flu-like reaction called metal fume disease and disturbances in the blood.Lithium is used to make glasses and pharmaceuticals. Lithium may cause diseases of the stomach, intestinal tract, central nervous system, and kidneys.Overexposure to silver may cause a gray discoloration of the skin, hair and internal organs. Additional symptoms may include nausea, vomiting, and diarrhea.Zinc overexposure may cause the flu-like symptoms of metal fume fever; stomach and intestinal disturbances; and/or liver dysfunction.Overexposure to bismuth may cause extreme drowsiness (somnolence) and neurologic disturbances such as confusion, difficulty in concentration, hallucinations, delusions, myoclonic jerks, tremors, seizures, an impaired ability to coordinate voluntary movements (ataxia), and/or inability to stand or walk.Overexposure to gold (as in treatment of rheumatoid arthritis) may cause skin rashes; bone marrow depression; stomach and intestinal bleeding; headaches; vomiting; focal or generalized continuous fine vibrating muscle movements (myokymia); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).Some cases of overexposure to nickel have been associated an increased risk of lung cancer.Overexposure to selenium may cause irritation of the respiratory system, gastrointestinal tract, and eyes; inflammation of the liver; loss of hair (alopecia); loss of skin color (depigmentation); and peripheral nerve damage.Overexposure to tin may damage the nervous system and cause psychomotor disturbances including tremor, convulsions, hallucinations, and psychotic behavior.Aluminum containers used in the manufacture and processing of some foods, cosmetics and medicines, and also for water purification. Overexposure to aluminum may cause brain damage (encephalopathy). | Symptoms of Heavy Metal Poisoning. The symptoms of heavy metal poisoning vary according to which type of metal overexposure is involved. Some specific examples are:ARSENIC POISONINGArsenic is used in the manufacture of pesticides. The gas from arsenic also has some industrial uses. Overexposure may cause headaches, drowsiness, confusion, seizures, and life-threatening complications. Neurological symptoms include brain damage (encephalopathy), nerve disease of the extremities (peripheral neuropathy), pericapillary hemorrhages within the white matter, and loss or deficiency of the fatty coverings (myelin) around these nerve fibers (demyelination). Skin problems include transverse white bands on the fingernails (mees' lines) and excessive accumulation of fluid in the soft layers of tissue below the skin (edema). Gastrointestinal symptoms include a flu-like illness (gastroenteritis) that is characterized by vomiting; abdominal pain; fever; and diarrhea, which, in some cases, may be bloody. Other symptoms include breakdown of the hemoglobin of red blood cells (hemolysis), a low level of iron in the red blood cells (anemia), and low blood pressure (hypotension). Some individuals may experience a garlic-like odor that may be detectable on the breath.In cases of chronic poisoning, weakness, muscle aches, chills, and fever may develop. The onset of symptoms in chronic arsenic poisoning is about two to eight weeks after exposure. Skin and nail symptoms include hardened patches of skin (hyperkeratosis) with unusually deep creases on the palms of the hands and the soles of the feet, unusual darkening of certain areas of the skin (hyperpigmentation), transverse white bands on the fingernails (mees' lines), and a scale like inflammation of the skin (exfoliative dermatitis). Other symptoms include inflammation of sensory and motor nerves (polyneuritis) and the mucose membrane lining the throat.Inorganic arsenic accumulates in the liver, spleen, kidneys, lungs, and gastrointestinal tract. It then passes through these sites but leaves a residue in tissues such as skin, hair, and nails. Symptoms of acute inorganic arsenic poisoning include severe burning of the mouth and throat, abdominal pain, nausea, vomiting, diarrhea, low blood pressure (hypotension), and muscle spasms. Individuals with severe inorganic arsenic poisoning may experience heart problems (cardiomyopathy); accumulation of acid in the tubes of the kidneys (renal tubular acidosis); breakdown of the hemoglobin of red blood cells (hemolysis); irregular heart rhythms (ventricular arrhythmias); coma; seizures; bleeding within the intestines (intestinal hemorrhage); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).CADMIUM POISONINGCadmium is used for many items, including electroplating, storage batteries, vapor lamps and in some solders. The onset of symptoms may be delayed for two to four hours after exposure. Overexposure may cause fatigue, headaches, nausea, vomiting, abdominal cramps, diarrhea, and fever. In addition, progressive loss of lung function (emphysema), abnormal buildup of fluid within the lungs (pulmonary edema), and breathlessness (dyspnea) may also be present. In some cases, affected individuals may exhibit increased salivation; yellowing of the teeth; an unusually rapid heart beat (tachycardia); low levels of iron within the red blood cells (anemia); bluish discoloration (cyanosis) of the skin and mucous membranes due to insufficient oxygen supply to these tissues; and/or an impaired sense of smell (anosmia). Individuals with cadmium poisoning may also experience improper functioning of the canals with the kidney (renal tubular dysfunction) characterized by excretion of abnormally high levels of protein in the urine (proteinuria), minor changes in liver function, and/or softening of certain bones (osteomalacia).CHROMIUM POISONINGChromium is used in the manufacture of cars, glass, pottery and linoleum. Exposure to too much chromium may cause lung and respiratory tract cancer as well as kidney diseases. In addition, overexposure to chromium may also cause gastrointestinal symptoms, such as diarrhea and vomiting, often with blood. Symptoms may lead to severe water-electrolyte disorders, increased mild acidity of blood and body tissues (acidosis), and/or inadequate blood flow to its tissues resulting in shock. Lesions on the kidneys, liver, and muscular layer of the heart (myocardium) may also develop.COBALT POISONINGCobalt, used in making jet engines, may cause nausea, vomiting, lack of appetite (anorexia), ear ringing (tinnitus), nerve damage, respiratory diseases, an unusually large thyroid gland (goiter), and/or heart and/or kidney damage.LEAD POISONINGLead production workers, battery plant workers, welders and solders may be overexposed to lead if proper precautions are not taken. Lead is stored in the bone but may affect any organ system. The effects of lead poisoning varies depending on the age of the individual and the amount of exposure.In children, symptoms vary depending upon the degree of exposure to lead. Some affected individuals may not have any noticeable symptoms. Symptoms usually develop over a three to six week time period. Lead overexposure may cause children to be less playful, clumsier, irritable, and sluggish (lethargic). In some cases, symptoms include headaches, vomiting, abdominal pain, lack of appetite (anorexia), constipation, slurred speech (dysarthria), changes in kidney function, unusually high amounts of protein in the blood (hyperproteinemia), and unusually pale skin (pallor) resulting from a low level of iron in the red blood cells (anemia). Neurological symptoms associated with lead overexposure include an impaired ability to coordinate voluntary movements (ataxia), brain damage (encephalopathy), seizures, convulsions, swelling of the optic nerve (papilledema), and/or impaired consciousness. Some affected children experience learning or behavioral problems such as mental retardation and selective deficits in language, cognitive function, balance, behavior, and school performance. In some cases, symptoms may be life-threatening.In adults, overexposure to lead may cause high blood pressure and damage to the reproductive organs. Additional symptoms may include fever, headaches, fatigue, sluggishness (letheragy), vomiting, loss of appetite (anorexia), abdominal pain, constipation, joint pain, loss of recently acquired skills, incoordination, listlessness, difficulty sleeping (insomnia), irritability, altered consciousness, hallucinations, and/or seizures. In addition, affected individuals may experience low levels of iron in the red blood cells (anemia), peripheral neuropathy, and, in some cases, brain damage (encephalopathy). Some affected individuals experience decreased muscle strength and endurance; kidney disease; wrist drop; and behavioral changes such as hostility, depression, and/or anxiety. In some cases, symptoms may be life-threatening.Lead is excreted in urine and feces. However, it may also appear in hair, nails, sweat, saliva, and breast milk.MANGANESE POISONINGManganese is used as a purifying agent in the production of several metals. Symptoms associated with overexposure to manganese may include damage to the central nervous system and pneumonia. Additional symptoms and physical findings include weakness, fatigue, confusion, hallucinations, odd or awkward manner of walking (gait), muscle spasms (dystonia), rigidity of the trunk, stiffness, awkwardness of the limbs, tremors of the hands, and psychiatric abnormalities.MERCURY POISONINGMercury is used by dental assistants and hygienists, and chemical workers. Mercury can affect the lungs, kidneys, brain, and/or skin. Symptoms of mercury poisoning include fatigue, depression, sluggishness (letheragy), irritability, and headaches.Respiratory symptoms associated with inhalation to mercury vapors include coughing, breathlessness (dyspnea), tightness or burning pain in the chest, and/or respiratory distress. Some affected individuals may experience abnormal buildup of fluid in the lungs (pulmonary edema); pneumonia; and/or abnormal formation of fibrous tissue (fibrosis).There may be behavioral and neurological changes associated with overexposure to mercury poisoning, such as excitability and quick-tempered behavior, lack of concentration, and loss of memory. Shock and permanent brain damage may also be result from mercury poisoning. Some affected individuals experience mental confusion. A progressive cerebellar syndrome with impaired ability to coordinate voluntary movements (ataxia) of the arms may also be present. Abnormal involuntary movements of the body such as uncontrolled jerky movements combined with slow, writhing movements (choreoathetosis) are common. Additional symptoms include non-inflammatory degenerative disease of the nerves (polyneuropathy); impaired ability to coordinate voluntary movements (cerebellar ataxia); tremors of the legs and arms and, in some cases, of the tongue and lips; seizures; and/or slurred speech (dysarthria). Changes in mood, behavior, and consciousness may also occur.In some cases of chronic exposure to inorganic mercury a personality disorder known as erethism or mad hatter syndrome may occur. Symptoms associated with mad hatter syndrome include memory loss, excessive shyness, abnormal excitability, and/or insomnia. This syndrome was described in workers with occupational exposure to mercury in the felt-hat industry.Many affected individual experience sensory impairments such as visual problems (e.g. constriction of visual fields, tunnel vision, and blindness) as well as hearing loss.Some individuals may experience skin changes such as painful swelling and pink coloration of the fingers and toes (acrodynia); persistent redness or inflammation of the skin (erythema); extreme sensitivity (hyperesthesia) of the affected areas; and tingling and sensory disturbances.In some cases, other affected individuals may experience stomach and intestinal disturbances; kidney damage; dehydration; acute renal failure; inflammation of the gums (gingivitis); severe local irritation of the mouth and pharynx, accompanied by vomiting; and/or abdominal cramps with bloody diarrhea.Mercury is mainly excreted through the urine and feces.PHOSPHORUS POISONINGSymptoms associated with phosphorus poisoning include weakness, headaches, vomiting, sweating, abdominal cramps, salivation, wheezing secondary to bronchial spasm, drooping of the upper eyelids (ptosis), contraction of the pupil (miosis), and/or muscular weakness and twitching. In addition, non-inflammatory degenerative disease of the sensorimotor nerves (sensorimotor polyneuropathy) may advance to progressive deterioration (atrophy). In some cases, respiratory paralysis may also occur.THALLIUM POISONINGSymptoms associated with thallium poisoning include extreme drowsiness (somnolence), nausea, vomiting, abdominal pain, and bloody vomiting (hematemesis). Some affected individuals may experience the loss of most or all of their scalp hair (alopecia); rapidly progressive and painful sensory polyneuropathy; motor neuropathy; cranial nerve palsies; seizures; impaired ability to coordinate voluntary movements (cerebellar ataxia); and/or mental retardation. Some individuals may experience eye symptoms including wasting away (atrophy) of the optic nerve (optic atrophy), inflammation of the optic nerve (retrobulbar neuritis), and impaired functioning of the muscles of the eyes (ophthalmoplegia). In some cases, thallium poisoning may progress to include renal and cardiac failure, confusion, psychosis, organic brain syndrome, and/or coma.ADDITIONAL METAL POISONINGSAdditional metals that may cause poisoning include antimony, aluminum, barium, bismuth, copper, gold, iron, lithium, platinum, silver, tin, and zinc. Common symptoms of poisoning from these metals may include gastrointestinal, renal, and neurological symptoms, such as headaches, irritability, psychosis, stupor, coma, and convulsions.Antimony is used for hardening lead, and in the manufacture of batteries and cables. It may possibly cause lung disease and skin cancer, especially in those who smoke.Copper is used in the manufacture of electrical wires. It may cause a flu-like reaction called metal fume disease and disturbances in the blood.Lithium is used to make glasses and pharmaceuticals. Lithium may cause diseases of the stomach, intestinal tract, central nervous system, and kidneys.Overexposure to silver may cause a gray discoloration of the skin, hair and internal organs. Additional symptoms may include nausea, vomiting, and diarrhea.Zinc overexposure may cause the flu-like symptoms of metal fume fever; stomach and intestinal disturbances; and/or liver dysfunction.Overexposure to bismuth may cause extreme drowsiness (somnolence) and neurologic disturbances such as confusion, difficulty in concentration, hallucinations, delusions, myoclonic jerks, tremors, seizures, an impaired ability to coordinate voluntary movements (ataxia), and/or inability to stand or walk.Overexposure to gold (as in treatment of rheumatoid arthritis) may cause skin rashes; bone marrow depression; stomach and intestinal bleeding; headaches; vomiting; focal or generalized continuous fine vibrating muscle movements (myokymia); and yellowing of the skin, mucous membranes, and whites of the eyes (jaundice).Some cases of overexposure to nickel have been associated an increased risk of lung cancer.Overexposure to selenium may cause irritation of the respiratory system, gastrointestinal tract, and eyes; inflammation of the liver; loss of hair (alopecia); loss of skin color (depigmentation); and peripheral nerve damage.Overexposure to tin may damage the nervous system and cause psychomotor disturbances including tremor, convulsions, hallucinations, and psychotic behavior.Aluminum containers used in the manufacture and processing of some foods, cosmetics and medicines, and also for water purification. Overexposure to aluminum may cause brain damage (encephalopathy). | 556 | Heavy Metal Poisoning |
nord_556_2 | Causes of Heavy Metal Poisoning | Heavy metal poisoning is a result of the toxic accumulation of certain metals. Such metals compete with and replace certain essential minerals in the course of which any of several of the body's organ systems may be affected.Arsenic poisoning may be caused by medications including Fowler's solution (potassium arsenite) and some topical creams used in the treatment of some skin conditions. Ingestion of herbicides, insecticides, pesticides, fungicides, or rodenticides containing arsenic may cause arsenic poisoning. Occupational exposure to arsenic in the manufacture of paints, enamels, glass, and metals may cause arsenic poisoning. Other forms of occupational exposure include galvanizing, soldering, etching, lead plating, smelting, and wood preserving. Arsenic is also found in contaminated water, seafood, and algae.Cadmium poisoning may be caused by ingestion of food (e.g. grains, cereals, and leafy vegetables) and cigarette smoke. Occupational exposure to cadmium in metal plating, battery, and plastics industries may also occur.Lead poisoning may be caused by exposure (e.g. chewing or ingestion) to deteriorating lead paint in older houses. Occupational exposure to lead in painting, smelting, firearms instruction, automotive repair, brass or cooper foundries, printing, battery manufacturing, mining, brass foundry, gasoline, glass, and bridge, tunnel and elevated highway construction may also occur. Another cause of lead poisoning is through the contamination of water from lead pipes. Additional causes of lead poisoning include calcium products, progressive hair dyes, kajal, surma, kohl, and foreign digestive remedies.Manganese poisoning may be caused by chronic inhalation and ingestion of manganese particles. Occupational exposure to manganese in mining and separating manganese ore may also occur.Mercury poisoning may be caused by exposure to large amounts of mercury in the manufacturing of thermometers, mirrors, incandescent lights, x-ray machines, and vacuum pumps. Another cause of mercury poisoning is contaminated water and fish. Children often are exposed to mercury through paint, calomel, teething powder, and mercuric fungicide used in washing diapers. Additional causes of mercury poisoning is exposure to mercury in thermometers, dental amalgams, and some batteries.Phosphorus poisoning may be caused by insecticides such as tetraethylpyrophosphate.Thallium poisoning may be caused by ingestion of rodenticides containing thallium. Thallium in pesticides, insecticides, metal alloys, and fireworks can be absorbed through skin as well as through ingestion and inhalation. | Causes of Heavy Metal Poisoning. Heavy metal poisoning is a result of the toxic accumulation of certain metals. Such metals compete with and replace certain essential minerals in the course of which any of several of the body's organ systems may be affected.Arsenic poisoning may be caused by medications including Fowler's solution (potassium arsenite) and some topical creams used in the treatment of some skin conditions. Ingestion of herbicides, insecticides, pesticides, fungicides, or rodenticides containing arsenic may cause arsenic poisoning. Occupational exposure to arsenic in the manufacture of paints, enamels, glass, and metals may cause arsenic poisoning. Other forms of occupational exposure include galvanizing, soldering, etching, lead plating, smelting, and wood preserving. Arsenic is also found in contaminated water, seafood, and algae.Cadmium poisoning may be caused by ingestion of food (e.g. grains, cereals, and leafy vegetables) and cigarette smoke. Occupational exposure to cadmium in metal plating, battery, and plastics industries may also occur.Lead poisoning may be caused by exposure (e.g. chewing or ingestion) to deteriorating lead paint in older houses. Occupational exposure to lead in painting, smelting, firearms instruction, automotive repair, brass or cooper foundries, printing, battery manufacturing, mining, brass foundry, gasoline, glass, and bridge, tunnel and elevated highway construction may also occur. Another cause of lead poisoning is through the contamination of water from lead pipes. Additional causes of lead poisoning include calcium products, progressive hair dyes, kajal, surma, kohl, and foreign digestive remedies.Manganese poisoning may be caused by chronic inhalation and ingestion of manganese particles. Occupational exposure to manganese in mining and separating manganese ore may also occur.Mercury poisoning may be caused by exposure to large amounts of mercury in the manufacturing of thermometers, mirrors, incandescent lights, x-ray machines, and vacuum pumps. Another cause of mercury poisoning is contaminated water and fish. Children often are exposed to mercury through paint, calomel, teething powder, and mercuric fungicide used in washing diapers. Additional causes of mercury poisoning is exposure to mercury in thermometers, dental amalgams, and some batteries.Phosphorus poisoning may be caused by insecticides such as tetraethylpyrophosphate.Thallium poisoning may be caused by ingestion of rodenticides containing thallium. Thallium in pesticides, insecticides, metal alloys, and fireworks can be absorbed through skin as well as through ingestion and inhalation. | 556 | Heavy Metal Poisoning |
nord_556_3 | Affects of Heavy Metal Poisoning | Heavy metal poisoning can affect males and females in equal numbers, depending on exposure. Outbreaks of this type of poisoning have occurred in the United States during the past several years from imported plates and cookware that were not properly coated to prevent heavy metals from contaminating food.In the United States, lead poisoning most often affects children between one and three years old.Lead poisoning affects adults less often than children. In the last 20 years, statistics show the number of children with potentially harmful blood lead levels has dropped 85 percent.Mercury poisoning is unusual in children. There have been large outbreaks in Australia and France of bismuth poisoning. | Affects of Heavy Metal Poisoning. Heavy metal poisoning can affect males and females in equal numbers, depending on exposure. Outbreaks of this type of poisoning have occurred in the United States during the past several years from imported plates and cookware that were not properly coated to prevent heavy metals from contaminating food.In the United States, lead poisoning most often affects children between one and three years old.Lead poisoning affects adults less often than children. In the last 20 years, statistics show the number of children with potentially harmful blood lead levels has dropped 85 percent.Mercury poisoning is unusual in children. There have been large outbreaks in Australia and France of bismuth poisoning. | 556 | Heavy Metal Poisoning |
nord_556_4 | Related disorders of Heavy Metal Poisoning | Symptoms of the following disorders can be similar to those of heavy metal poisoning. Comparisons may be useful for a differential diagnosis:Metal fume fever includes a variety of symptoms, such as a general feeling of ill health (malaise), chills, and fever. Affected individuals may have excessive thirst and a metallic taste in their mouth. Symptoms usually subside spontaneously in six to 12 hours. A classic case would occur when galvanized steel is welded in a poorly ventilated area.The following disorders may be associated with heavy metal poisoning as secondary characteristics. They are not necessary for a differential diagnosis.Fanconi's anemia is a blood disorder, which is a familial form of aplastic anemia. Children with this disorder bruise easily and experience nosebleeds. It may be caused by genetic and environmental interactions. Fanconi's syndrome can be acquired instead of inherited due to acute lead poisoning. (For more information on this disorder, choose “Fanconi's Anemia” as your search term in the Rare Disease Database.)Wilson's disease is a genetic disorder characterized by excess storage of copper in the body's tissues, particularly in the liver, brain and corneas of the eyes. The disorder occurs without overexposure to copper and is due to a metabolic defect. (For more information on this disorder, choose “Wilson Disease” as your search term in the Rare Disease Database.) | Related disorders of Heavy Metal Poisoning. Symptoms of the following disorders can be similar to those of heavy metal poisoning. Comparisons may be useful for a differential diagnosis:Metal fume fever includes a variety of symptoms, such as a general feeling of ill health (malaise), chills, and fever. Affected individuals may have excessive thirst and a metallic taste in their mouth. Symptoms usually subside spontaneously in six to 12 hours. A classic case would occur when galvanized steel is welded in a poorly ventilated area.The following disorders may be associated with heavy metal poisoning as secondary characteristics. They are not necessary for a differential diagnosis.Fanconi's anemia is a blood disorder, which is a familial form of aplastic anemia. Children with this disorder bruise easily and experience nosebleeds. It may be caused by genetic and environmental interactions. Fanconi's syndrome can be acquired instead of inherited due to acute lead poisoning. (For more information on this disorder, choose “Fanconi's Anemia” as your search term in the Rare Disease Database.)Wilson's disease is a genetic disorder characterized by excess storage of copper in the body's tissues, particularly in the liver, brain and corneas of the eyes. The disorder occurs without overexposure to copper and is due to a metabolic defect. (For more information on this disorder, choose “Wilson Disease” as your search term in the Rare Disease Database.) | 556 | Heavy Metal Poisoning |
nord_556_5 | Diagnosis of Heavy Metal Poisoning | The diagnosis of arsenic poisoning can be confirmed by discovering increased levels of arsenic in the hair, nails, and urine. An x-ray of abdomen may show ingested arsenic which is not penetrable by x-rays (radiopaque).The diagnosis of lead poisoning may be suspected based upon appreciation of the causative factors, a high index of suspicion, and certain laboratory tests for levels of lead in the blood. Other indicators of lead poisoning include an elevation of free erthrocytic protoporphyrins, inhibition of ALA-D activity, elevated lead in the hair, increased lead content of deciduous teeth, estimation of urinary coproporphytins, zinc protoporphyrin levels. A spinal tap may also be helpful in the diagnosis of lead poisoning. The LEADCARE In Office Test System has been approved by the FDA as a portable blood lead screening kit for health professionals' use to test for lead poisoning. | Diagnosis of Heavy Metal Poisoning. The diagnosis of arsenic poisoning can be confirmed by discovering increased levels of arsenic in the hair, nails, and urine. An x-ray of abdomen may show ingested arsenic which is not penetrable by x-rays (radiopaque).The diagnosis of lead poisoning may be suspected based upon appreciation of the causative factors, a high index of suspicion, and certain laboratory tests for levels of lead in the blood. Other indicators of lead poisoning include an elevation of free erthrocytic protoporphyrins, inhibition of ALA-D activity, elevated lead in the hair, increased lead content of deciduous teeth, estimation of urinary coproporphytins, zinc protoporphyrin levels. A spinal tap may also be helpful in the diagnosis of lead poisoning. The LEADCARE In Office Test System has been approved by the FDA as a portable blood lead screening kit for health professionals' use to test for lead poisoning. | 556 | Heavy Metal Poisoning |
nord_556_6 | Therapies of Heavy Metal Poisoning | TreatmentThe main treatment of heavy metal poisoning is termination of exposure to the metal. Treatment also consists of the use of various chelating agents that cause the toxic (poison) element to bind with the drug and be excreted in the urine. Three common drugs for treatment of metal poisoning are: BA. (Dimercaprol), Calcium EDTA (Calcium Disodium Versenate) and Penicillamine. Each of these work by binding actions that permit the metals to be eliminated from the body through the urine.Treatment should also be symptomatic and supportive. In some cases, pumping of the stomach (gastric lavage) will remove some ingested metals. In the case of inhaled poisons, affected individuals should be removed from the contaminated environment and their respiration supported.Occupational exposure to heavy metals requires prevention through the use of masks and protective clothing.In cases of swelling of the brain (cerebral edema), treatment with a diuretic called Mannitol, and corticosteroid drugs, along with intracranial monitoring, is required.Kidney failure may call for hemodialysis and/or other special treatment.In 1991 the FDA approved the drug succimer (Chemet) for the treatment of children with severe lead poisoning. Chemet is manufactured by Johnson & Johnson Co.There is no proven effective therapy for the treatment of cadmium poisoning. | Therapies of Heavy Metal Poisoning. TreatmentThe main treatment of heavy metal poisoning is termination of exposure to the metal. Treatment also consists of the use of various chelating agents that cause the toxic (poison) element to bind with the drug and be excreted in the urine. Three common drugs for treatment of metal poisoning are: BA. (Dimercaprol), Calcium EDTA (Calcium Disodium Versenate) and Penicillamine. Each of these work by binding actions that permit the metals to be eliminated from the body through the urine.Treatment should also be symptomatic and supportive. In some cases, pumping of the stomach (gastric lavage) will remove some ingested metals. In the case of inhaled poisons, affected individuals should be removed from the contaminated environment and their respiration supported.Occupational exposure to heavy metals requires prevention through the use of masks and protective clothing.In cases of swelling of the brain (cerebral edema), treatment with a diuretic called Mannitol, and corticosteroid drugs, along with intracranial monitoring, is required.Kidney failure may call for hemodialysis and/or other special treatment.In 1991 the FDA approved the drug succimer (Chemet) for the treatment of children with severe lead poisoning. Chemet is manufactured by Johnson & Johnson Co.There is no proven effective therapy for the treatment of cadmium poisoning. | 556 | Heavy Metal Poisoning |
nord_557_0 | Overview of Hemimegalencephaly | Hemimegalencephaly (HME) is a rare neurological condition in which one-half of the brain, or one side of the brain, is abnormally larger than the other. The structure of the brain on the affected side may be markedly abnormal or show only subtle changes. In either case, as a consequence of this size and structural differences, the enlarged brain tissue causes frequent seizures, often associated with cognitive or behavioral disabilities. Seizures in association with HME often begin in early infant life including an association with infantile spasms. Hemimegalencephaly may occur as an isolated or sporadic brain malformation or it may be associated with other neurodevelopmental syndromes. Thus, when detected, HME should prompt a search for other syndromic diagnoses.Anti-seizure medications typically are not effective in controlling seizures in HME and thus, surgery is often recommended to control the seizures. If the affected side is surgically removed (anatomic hemispherectomy) or disconnected from the other brain structures (functional hemispherectomy), the remaining side of the brain may gradually take over the functions normally performed by the affected side.Any combination of altered mental status, seizures, enlarged head, and /or altered skin pigmentation should prompt consideration of HME. In general, the presence of HME is definitively diagnosed by brain MRI. With the evolution of more widespread fetal imaging including ultrasound and MRI, a number of HME cases are detected prenatally. | Overview of Hemimegalencephaly. Hemimegalencephaly (HME) is a rare neurological condition in which one-half of the brain, or one side of the brain, is abnormally larger than the other. The structure of the brain on the affected side may be markedly abnormal or show only subtle changes. In either case, as a consequence of this size and structural differences, the enlarged brain tissue causes frequent seizures, often associated with cognitive or behavioral disabilities. Seizures in association with HME often begin in early infant life including an association with infantile spasms. Hemimegalencephaly may occur as an isolated or sporadic brain malformation or it may be associated with other neurodevelopmental syndromes. Thus, when detected, HME should prompt a search for other syndromic diagnoses.Anti-seizure medications typically are not effective in controlling seizures in HME and thus, surgery is often recommended to control the seizures. If the affected side is surgically removed (anatomic hemispherectomy) or disconnected from the other brain structures (functional hemispherectomy), the remaining side of the brain may gradually take over the functions normally performed by the affected side.Any combination of altered mental status, seizures, enlarged head, and /or altered skin pigmentation should prompt consideration of HME. In general, the presence of HME is definitively diagnosed by brain MRI. With the evolution of more widespread fetal imaging including ultrasound and MRI, a number of HME cases are detected prenatally. | 557 | Hemimegalencephaly |
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