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Overview of Leber Congenital Amaurosis
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Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or a cone shape to the front of the eye (keratoconus). LCA is usually inherited as an autosomal recessive genetic condition.
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Overview of Leber Congenital Amaurosis. Leber congenital amaurosis (LCA) is a rare genetic eye disorder. Affected infants are often blind at birth. Other symptoms may include crossed eyes (strabismus); rapid, involuntary eye movements (nystagmus); unusual sensitivity to light (photophobia); clouding of the lenses of the eyes (cataracts); and/or a cone shape to the front of the eye (keratoconus). LCA is usually inherited as an autosomal recessive genetic condition.
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Symptoms of Leber Congenital Amaurosis
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Children born with LCA have light-gathering cells (rods and cones) of the retina that do not function properly. Absence or reduction of the electrical activity of the retina is always observed and is necessary for the diagnosis of LCA.A decrease in visual responsiveness at birth is the first sign of the disease. Often the child will poke, press and rub the eyes to stimulate the retina to produce light (Franceschetti’s oculo-digital sign).This activity may cause the eyes to become sunken or deep set (enophthalmos).Other symptoms may include strabismus; nystagmus; photophobia; cataracts; and/or keratoconus. In addition, some infants may exhibit hearing loss, intellectual disability, and/or developmental delay.Specific types of LCA have been defined based on the causative gene. Some types are associated with little change in vision over time (stationary disease) while others become more severe over time (progressive disease).
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Symptoms of Leber Congenital Amaurosis. Children born with LCA have light-gathering cells (rods and cones) of the retina that do not function properly. Absence or reduction of the electrical activity of the retina is always observed and is necessary for the diagnosis of LCA.A decrease in visual responsiveness at birth is the first sign of the disease. Often the child will poke, press and rub the eyes to stimulate the retina to produce light (Franceschetti’s oculo-digital sign).This activity may cause the eyes to become sunken or deep set (enophthalmos).Other symptoms may include strabismus; nystagmus; photophobia; cataracts; and/or keratoconus. In addition, some infants may exhibit hearing loss, intellectual disability, and/or developmental delay.Specific types of LCA have been defined based on the causative gene. Some types are associated with little change in vision over time (stationary disease) while others become more severe over time (progressive disease).
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Causes of Leber Congenital Amaurosis
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LCA is a monogenic disease and at least 27 genes are implicated. Changes (mutations) in these genes can account for about 80-90% of diagnosed cases of LCA. The genes responsible for the remaining 10-20% of diagnoses are not known. LCA is usually inherited as an autosomal recessive genetic condition. Twenty-four of the genes associated with LCA cause only recessive disease. Two genes (IMPDH1 and OTX2) are known to cause dominant disease. One gene (CRX) is known to cause either dominant or recessive disease, depending on the specific mutation.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 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 have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.There are about 20,000 different genes in a human and all individuals carry one copy of several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.In rare cases, LCA is inherited as an autosomal dominant genetic disorder. Mutations in three genes, CRX, IMPDH1, and OTX2 are currently known to be associated with this type of LCA.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 in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
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Causes of Leber Congenital Amaurosis. LCA is a monogenic disease and at least 27 genes are implicated. Changes (mutations) in these genes can account for about 80-90% of diagnosed cases of LCA. The genes responsible for the remaining 10-20% of diagnoses are not known. LCA is usually inherited as an autosomal recessive genetic condition. Twenty-four of the genes associated with LCA cause only recessive disease. Two genes (IMPDH1 and OTX2) are known to cause dominant disease. One gene (CRX) is known to cause either dominant or recessive disease, depending on the specific mutation.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 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 have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.There are about 20,000 different genes in a human and all individuals carry one copy of several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.In rare cases, LCA is inherited as an autosomal dominant genetic disorder. Mutations in three genes, CRX, IMPDH1, and OTX2 are currently known to be associated with this type of LCA.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 in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
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Affects of Leber Congenital Amaurosis
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The prevalence of LCA has been estimated to be 1-2/100,000 births. This disorder affects males and females in equal numbers.
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Affects of Leber Congenital Amaurosis. The prevalence of LCA has been estimated to be 1-2/100,000 births. This disorder affects males and females in equal numbers.
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Related disorders of Leber Congenital Amaurosis
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Symptoms of the following disorders can be similar to those of Leber congenital amaurosis. Comparisons may be useful for a differential diagnosis:Loken-Senior syndrome is a rare autosomal recessive genetic disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. (For more information on this disorder, choose “Loken-Senior” as your search term in the Rare Disease Database.)Joubert syndrome is an autosomal recessive genetic disorder that affects the area of the brain that controls balance and coordination. This condition is characterized by a specific finding on an MRI called a “molar tooth sign” in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal. The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements and low muscle tone. (For more information on this disorder, choose “Joubert” as your search term in the Rare Disease Database.)Zellweger spectrum disorders are a group of rare, autosomal recessive genetic, multisystem disorders that were once thought to be separate entities. These disorders are also known as peroxisome biogenesis disorders (PBDs), a group of disorders characterized by the failure of the body to produce peroxisomes that function properly. Zellweger syndrome is the most severe form; neonatal adrenoleukodystrophy is the intermediate form; and infantile Refsum disease is the mildest form. Zellweger spectrum disorders can affect most organs of the body. Neurological deficits, loss of muscle tone (hypotonia), hearing loss, vision problems, liver dysfunction, and kidney abnormalities are common findings. (For more information on this disorder, choose “Zellweger” as your search term in the Rare Disease Database.)
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Related disorders of Leber Congenital Amaurosis. Symptoms of the following disorders can be similar to those of Leber congenital amaurosis. Comparisons may be useful for a differential diagnosis:Loken-Senior syndrome is a rare autosomal recessive genetic disorder characterized by progressive wasting of the filtering unit of the kidney (nephronophthisis), with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life. (For more information on this disorder, choose “Loken-Senior” as your search term in the Rare Disease Database.)Joubert syndrome is an autosomal recessive genetic disorder that affects the area of the brain that controls balance and coordination. This condition is characterized by a specific finding on an MRI called a “molar tooth sign” in which the cerebellar vermis of the brain is absent or underdeveloped and the brain stem is abnormal. The most common features of Joubert syndrome are lack of muscle control (ataxia), abnormal breathing patterns (hyperpnea), sleep apnea, abnormal eye and tongue movements and low muscle tone. (For more information on this disorder, choose “Joubert” as your search term in the Rare Disease Database.)Zellweger spectrum disorders are a group of rare, autosomal recessive genetic, multisystem disorders that were once thought to be separate entities. These disorders are also known as peroxisome biogenesis disorders (PBDs), a group of disorders characterized by the failure of the body to produce peroxisomes that function properly. Zellweger syndrome is the most severe form; neonatal adrenoleukodystrophy is the intermediate form; and infantile Refsum disease is the mildest form. Zellweger spectrum disorders can affect most organs of the body. Neurological deficits, loss of muscle tone (hypotonia), hearing loss, vision problems, liver dysfunction, and kidney abnormalities are common findings. (For more information on this disorder, choose “Zellweger” as your search term in the Rare Disease Database.)
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Diagnosis of Leber Congenital Amaurosis
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Electroretinography (ERG) is used to assess visual function by measuring activity in the retina. Infants with LCA have absent or reduced electrical activity of the retina. Molecular genetic testing is available for mutations in the genes associated with LCA. Clinical signs and symptoms can be helpful in determining which genes to test for, and in what order.
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Diagnosis of Leber Congenital Amaurosis. Electroretinography (ERG) is used to assess visual function by measuring activity in the retina. Infants with LCA have absent or reduced electrical activity of the retina. Molecular genetic testing is available for mutations in the genes associated with LCA. Clinical signs and symptoms can be helpful in determining which genes to test for, and in what order.
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Therapies of Leber Congenital Amaurosis
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Treatment
Treatment for LCA is symptomatic and supportive. Genetic counseling is recommended for families of affected children.In 2017, the gene therapy Luxturna (voretigene neparvovec-rzyl) was approved by the U.S. Food and Drug Administration (FDA) to treat children and adults with two mutations in the RPE65 gene which includes a type of LCA called LCA2. Luxturna is manufactured by Spark Therapeutics, Inc.
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Therapies of Leber Congenital Amaurosis. Treatment
Treatment for LCA is symptomatic and supportive. Genetic counseling is recommended for families of affected children.In 2017, the gene therapy Luxturna (voretigene neparvovec-rzyl) was approved by the U.S. Food and Drug Administration (FDA) to treat children and adults with two mutations in the RPE65 gene which includes a type of LCA called LCA2. Luxturna is manufactured by Spark Therapeutics, Inc.
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Overview of Leber Hereditary Optic Neuropathy
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Leber hereditary optic neuropathy (LHON) is often characterized by bilateral, painless subacute loss of central vision most commonly during young adult life. In most cases, symptoms begin with one eye first, followed a few weeks later by visual failure in the other eye. Extremely rarely there may be neurologic abnormalities, such as peripheral neuropathy, postural tremor, nonspecific myopathy, and movement disorders. LHON is caused by changes (called variants or mutations) in mitochondrial DNA and it is strictly transmitted by maternal inheritance. The prevalence of LHON in carriers and affected is approximately 1:50,000 people. Many carriers never suffer significant visual loss; males are about four to five times more likely than females to lose vision and be affected. The incidence of visual loss, therefore, is much less and about 1:10 million/year
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Overview of Leber Hereditary Optic Neuropathy. Leber hereditary optic neuropathy (LHON) is often characterized by bilateral, painless subacute loss of central vision most commonly during young adult life. In most cases, symptoms begin with one eye first, followed a few weeks later by visual failure in the other eye. Extremely rarely there may be neurologic abnormalities, such as peripheral neuropathy, postural tremor, nonspecific myopathy, and movement disorders. LHON is caused by changes (called variants or mutations) in mitochondrial DNA and it is strictly transmitted by maternal inheritance. The prevalence of LHON in carriers and affected is approximately 1:50,000 people. Many carriers never suffer significant visual loss; males are about four to five times more likely than females to lose vision and be affected. The incidence of visual loss, therefore, is much less and about 1:10 million/year
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Leber Hereditary Optic Neuropathy
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Symptoms of Leber Hereditary Optic Neuropathy
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Individuals with LHON typically display symptoms while young adult. If vision is lost, then it usually occurs before 40 years of age.The acute phase of LHON is characterized by a loss of central vision, including blurring and reduced perception of color. Individuals usually lose vision in one eye first and then lose vision in the other eye after two to three months. The atrophic phase is characterized by bilateral optic atrophy, resulting in lifelong blindness.Depending on the mutation and pedigree, most female carriers do not lose vision but up to half of males do.
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Symptoms of Leber Hereditary Optic Neuropathy. Individuals with LHON typically display symptoms while young adult. If vision is lost, then it usually occurs before 40 years of age.The acute phase of LHON is characterized by a loss of central vision, including blurring and reduced perception of color. Individuals usually lose vision in one eye first and then lose vision in the other eye after two to three months. The atrophic phase is characterized by bilateral optic atrophy, resulting in lifelong blindness.Depending on the mutation and pedigree, most female carriers do not lose vision but up to half of males do.
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Causes of Leber Hereditary Optic Neuropathy
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LHON is caused by genetic mutations in the mitochondrial DNA (mtDNA). Mothers with a LHON gene mutation may not show symptoms, but family history often reveals maternal relatives with visual loss at an early age.Mutations in mitochondrial DNA can only be inherited maternally because mitochondria derive from ova, not sperm. All of the offspring of a mother with an mtDNA mutation will inherit the gene. A male with a mitochondrial DNA mutation cannot transmit the mutated gene to any of his children.The three primary mitochondrial DNA LHON-causing mutations are mt.3460G>A, mt.11778G>A, and mt.14484T>C, which account for over 90% of LHON patients. The most common LHON-causing mutation is mt.11778G>A. The greatest penetrance (chance of a carrier to lose vision) is for mt.3460G>A and the least is for mt.14484T>C.
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Causes of Leber Hereditary Optic Neuropathy. LHON is caused by genetic mutations in the mitochondrial DNA (mtDNA). Mothers with a LHON gene mutation may not show symptoms, but family history often reveals maternal relatives with visual loss at an early age.Mutations in mitochondrial DNA can only be inherited maternally because mitochondria derive from ova, not sperm. All of the offspring of a mother with an mtDNA mutation will inherit the gene. A male with a mitochondrial DNA mutation cannot transmit the mutated gene to any of his children.The three primary mitochondrial DNA LHON-causing mutations are mt.3460G>A, mt.11778G>A, and mt.14484T>C, which account for over 90% of LHON patients. The most common LHON-causing mutation is mt.11778G>A. The greatest penetrance (chance of a carrier to lose vision) is for mt.3460G>A and the least is for mt.14484T>C.
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Affects of Leber Hereditary Optic Neuropathy
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The prevalence of visual loss from LHON is approximately 1:50,000 people. Most carriers never suffer significant visual loss; males are about four to five times more likely than females to lose vision and be affected.
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Affects of Leber Hereditary Optic Neuropathy. The prevalence of visual loss from LHON is approximately 1:50,000 people. Most carriers never suffer significant visual loss; males are about four to five times more likely than females to lose vision and be affected.
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Related disorders of Leber Hereditary Optic Neuropathy
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Symptoms of the following disorders are similar to LHON. Comparisons may be useful for a differential diagnosis:Autosomal dominant optic atrophy (DOA) is related to the OPA1 family of genes that influences mitochondrial biogenesis and function. The family pedigree is autosomal dominant. The symptoms tend to come on at an earlier age (6-9) than in LHON and to do so in a more insidious and milder way. Generally, before puberty the child develops slowly progressive loss of vision and central scotomas a mild optic atrophy that progresses until about 20 years of age to a moderate loss of vision and optic atrophy. This difference in tempo and symmetry as well as the different genetics allows for the distinction with LHON.Toxic or nutritional deficiencies can also produce bilateral mitochondrial optic neuropathy. There are several problems with metabolism that can lead to mitochondrial dysfunction that produces an acquired optic neuropathy that clinically seems very similar to these two genetic conditions (LHON, DOA).
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Related disorders of Leber Hereditary Optic Neuropathy. Symptoms of the following disorders are similar to LHON. Comparisons may be useful for a differential diagnosis:Autosomal dominant optic atrophy (DOA) is related to the OPA1 family of genes that influences mitochondrial biogenesis and function. The family pedigree is autosomal dominant. The symptoms tend to come on at an earlier age (6-9) than in LHON and to do so in a more insidious and milder way. Generally, before puberty the child develops slowly progressive loss of vision and central scotomas a mild optic atrophy that progresses until about 20 years of age to a moderate loss of vision and optic atrophy. This difference in tempo and symmetry as well as the different genetics allows for the distinction with LHON.Toxic or nutritional deficiencies can also produce bilateral mitochondrial optic neuropathy. There are several problems with metabolism that can lead to mitochondrial dysfunction that produces an acquired optic neuropathy that clinically seems very similar to these two genetic conditions (LHON, DOA).
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Diagnosis of Leber Hereditary Optic Neuropathy
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LHON is diagnosed based on ophthalmologic findings, which include specialized visual testing. The testing involves dilated fundus examination to identify characteristic changes in the optic disc and vascular changes during the acute phase, visual fields, electrophysiologic studies and imaging, particularly OCT. Molecular genetic testing for mitochondrial genes associated with LHON can be used to confirm diagnosis. Most affected individuals know if their family members also are affected by LHON.
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Diagnosis of Leber Hereditary Optic Neuropathy. LHON is diagnosed based on ophthalmologic findings, which include specialized visual testing. The testing involves dilated fundus examination to identify characteristic changes in the optic disc and vascular changes during the acute phase, visual fields, electrophysiologic studies and imaging, particularly OCT. Molecular genetic testing for mitochondrial genes associated with LHON can be used to confirm diagnosis. Most affected individuals know if their family members also are affected by LHON.
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Therapies of Leber Hereditary Optic Neuropathy
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Treatment
Affected individuals should receive supportive management and treatment through the usage of visual aids, occupational rehabilitation and local social services. Several studies have shown that therapies involving ubiquinone and idebenone may provide possible benefits during both the acute and chronic phases of the disorder. Affected individuals should avoid smoking and excessive alcohol consumption, which generate reactive oxygen species (ROS) producing or amplifying mitochondrial impairments. Clinical Testing and Work-Up
Consistent monitoring and surveillance of asymptomatic individuals with LHON-causing mutations is not necessary. However, if visual disturbance is experienced, affected individuals should immediately seek medical attention from an ophthalmologist or neuro-ophthalmologist.Individuals should follow-up frequent to their own circumstances and availability of local healthcare.Genetic counseling is recommended for patients and their families. The key to understanding is that female carriers always transmit the gene and male carriers never do.
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Therapies of Leber Hereditary Optic Neuropathy. Treatment
Affected individuals should receive supportive management and treatment through the usage of visual aids, occupational rehabilitation and local social services. Several studies have shown that therapies involving ubiquinone and idebenone may provide possible benefits during both the acute and chronic phases of the disorder. Affected individuals should avoid smoking and excessive alcohol consumption, which generate reactive oxygen species (ROS) producing or amplifying mitochondrial impairments. Clinical Testing and Work-Up
Consistent monitoring and surveillance of asymptomatic individuals with LHON-causing mutations is not necessary. However, if visual disturbance is experienced, affected individuals should immediately seek medical attention from an ophthalmologist or neuro-ophthalmologist.Individuals should follow-up frequent to their own circumstances and availability of local healthcare.Genetic counseling is recommended for patients and their families. The key to understanding is that female carriers always transmit the gene and male carriers never do.
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Overview of Legg Calvé Perthes Disease
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Legg-Calvé-Perthes disease (LCPD) is one of a group of disorders known as the osteochondroses. The osteochondroses typically are characterized by degeneration and subsequent regeneration of the growing end of a bone (epiphyses). In LCPD, the growing end of the upper portion of the thigh bone (femur) is affected. The upper section of the thigh bone is known as the head or “the ball” and connects to the hip in a depression or “socket”. This is the hip joint, which is a ball and socket joint. The disorder results from an unexplained interruption of the blood supply (ischemia) to the head of the femur, which causes degeneration (avascular necrosis) and deformity of the femoral head. Symptoms may include a limp with or without pain in the hip, knee, thigh, and/or groin; muscle spasms; and/or limited or restricted movement of the affected hip. The disease process seems to be self-limiting as new blood supplies are established (revascularization) and new healthy bone forms (re-ossifies) in the affected area. The exact cause for the temporary interruption of blood flow to the femoral epiphysis is not fully understood. Most cases appear to occur randomly for no apparent reason (sporadically).
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Overview of Legg Calvé Perthes Disease. Legg-Calvé-Perthes disease (LCPD) is one of a group of disorders known as the osteochondroses. The osteochondroses typically are characterized by degeneration and subsequent regeneration of the growing end of a bone (epiphyses). In LCPD, the growing end of the upper portion of the thigh bone (femur) is affected. The upper section of the thigh bone is known as the head or “the ball” and connects to the hip in a depression or “socket”. This is the hip joint, which is a ball and socket joint. The disorder results from an unexplained interruption of the blood supply (ischemia) to the head of the femur, which causes degeneration (avascular necrosis) and deformity of the femoral head. Symptoms may include a limp with or without pain in the hip, knee, thigh, and/or groin; muscle spasms; and/or limited or restricted movement of the affected hip. The disease process seems to be self-limiting as new blood supplies are established (revascularization) and new healthy bone forms (re-ossifies) in the affected area. The exact cause for the temporary interruption of blood flow to the femoral epiphysis is not fully understood. Most cases appear to occur randomly for no apparent reason (sporadically).
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Symptoms of Legg Calvé Perthes Disease
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The age of onset, severity, duration, and associated complications of Legg-Calvé-Perthes disease vary greatly from one person to another. Generally, the onset is slow and the progression is gradual. The disorder usually affects children between the ages of eight and ten years, with some instances occurring as early as age two or as late as age 12. The disease typically affects one leg (unilateral); however, in approximately 10% of cases, the condition may subsequently develop in the other leg (bilateral).In most children, the first symptom is a limp with or without pain. Affected children may experience pain in the hip, knee, thigh, and/or groin. In some cases, the pain may be limited (localized) to the knee or inner part of the thigh. In addition, affected children may also experience muscle spasms of the legs; loss of muscle mass (atrophy) of the front thigh muscles; limited or restricted movements of the hips; and/or inflammation of the membrane lining the hip joint (synovitis). As affected children age, they may also exhibit slightly differing lengths of their two legs (leg length discrepancy).In all cases, blood supply to the capital femoral epiphysis is re-established and degenerative (necrotic) bone is resorbed and rehardens (re-ossifies). This occurs without therapeutic intervention (spontaneously). The regenerated bone may be only slightly abnormal, misshapen, or significantly misshapen (e.g., abnormally flattened or unusually enlarged). In almost all cases, some shortening of the leg occurs, and in more severe cases, the femoral head may be deformed. The length of time between onset of LCPD and new bone formation may be as short as 18 months or as long as four years.When onset occurs during the ages of four to nine years, it is, depending on treatment, less likely that osteoarthritis will develop later in life than it is in children with onset after the age of 10. Affected individuals who present significant deformity during re-ossification of the capital femoral epiphysis have an increased risk of developing osteoarthritis later in life.
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Symptoms of Legg Calvé Perthes Disease. The age of onset, severity, duration, and associated complications of Legg-Calvé-Perthes disease vary greatly from one person to another. Generally, the onset is slow and the progression is gradual. The disorder usually affects children between the ages of eight and ten years, with some instances occurring as early as age two or as late as age 12. The disease typically affects one leg (unilateral); however, in approximately 10% of cases, the condition may subsequently develop in the other leg (bilateral).In most children, the first symptom is a limp with or without pain. Affected children may experience pain in the hip, knee, thigh, and/or groin. In some cases, the pain may be limited (localized) to the knee or inner part of the thigh. In addition, affected children may also experience muscle spasms of the legs; loss of muscle mass (atrophy) of the front thigh muscles; limited or restricted movements of the hips; and/or inflammation of the membrane lining the hip joint (synovitis). As affected children age, they may also exhibit slightly differing lengths of their two legs (leg length discrepancy).In all cases, blood supply to the capital femoral epiphysis is re-established and degenerative (necrotic) bone is resorbed and rehardens (re-ossifies). This occurs without therapeutic intervention (spontaneously). The regenerated bone may be only slightly abnormal, misshapen, or significantly misshapen (e.g., abnormally flattened or unusually enlarged). In almost all cases, some shortening of the leg occurs, and in more severe cases, the femoral head may be deformed. The length of time between onset of LCPD and new bone formation may be as short as 18 months or as long as four years.When onset occurs during the ages of four to nine years, it is, depending on treatment, less likely that osteoarthritis will develop later in life than it is in children with onset after the age of 10. Affected individuals who present significant deformity during re-ossification of the capital femoral epiphysis have an increased risk of developing osteoarthritis later in life.
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Causes of Legg Calvé Perthes Disease
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The symptoms of Legg-Calvé-Perthes disease develop due to damage to the growing portion (epiphysis) of the upper end of the thigh bone. This damage results from interruption of the blood supply (ischemia) to this region. This damages the bone-forming cells (osteoblasts) and resident bone cells (osteocytes) and results in degeneration (necrosis) and softening of the bone in this area. The upper end of thigh bone becomes fragile as bone mass is lost. It is possible that this fragile area may “fracture” internally, causing deformity. A thin line of decreased density (Caffey sign) may be apparent on the epiphysis, which may represent such a “fracture” within the bone (subchondral). Damaged bone may fragment and cause irregularities when blood flow to the affected area eventually resumes (revascularization). As the bone regrows and rehardens (re-ossifies), it may deform, resulting in permanent malformation of the upper thigh bone (e.g., abnormally flattened or unusually enlarged epiphysis).The exact, underlying cause of the interrupted blood flow is not fully understood. Multiple factors including environmental and genetic ones may play a role in the development of the disorder. Some risk factors or conditions that may play a role in the development of LCPD include low birth weight, delayed skeletal maturity, trauma, adverse social and economic conditions, exposure to tobacco smoke, or a positive family history of the disorder. Some researchers have theorized that disorders that disrupt or affect how the blood clots (coagulation disorders) such as thrombophilia play a role in some individuals. These disorders could lead to abnormal blood clot formation would cause the interrupted blood flow that characterizes LCPD.No one theory has been proven as the underlying or contributing cause(s) of LCPD and it is possible that different individuals may have a different underlying causes. More research is necessary to determine the complex interactions that ultimately bring about the disorder.In a handful of extremely rare familial instances, mutations in the COL2A1 gene have been linked to avascular necrosis of the head of the thigh bone in children.
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Causes of Legg Calvé Perthes Disease. The symptoms of Legg-Calvé-Perthes disease develop due to damage to the growing portion (epiphysis) of the upper end of the thigh bone. This damage results from interruption of the blood supply (ischemia) to this region. This damages the bone-forming cells (osteoblasts) and resident bone cells (osteocytes) and results in degeneration (necrosis) and softening of the bone in this area. The upper end of thigh bone becomes fragile as bone mass is lost. It is possible that this fragile area may “fracture” internally, causing deformity. A thin line of decreased density (Caffey sign) may be apparent on the epiphysis, which may represent such a “fracture” within the bone (subchondral). Damaged bone may fragment and cause irregularities when blood flow to the affected area eventually resumes (revascularization). As the bone regrows and rehardens (re-ossifies), it may deform, resulting in permanent malformation of the upper thigh bone (e.g., abnormally flattened or unusually enlarged epiphysis).The exact, underlying cause of the interrupted blood flow is not fully understood. Multiple factors including environmental and genetic ones may play a role in the development of the disorder. Some risk factors or conditions that may play a role in the development of LCPD include low birth weight, delayed skeletal maturity, trauma, adverse social and economic conditions, exposure to tobacco smoke, or a positive family history of the disorder. Some researchers have theorized that disorders that disrupt or affect how the blood clots (coagulation disorders) such as thrombophilia play a role in some individuals. These disorders could lead to abnormal blood clot formation would cause the interrupted blood flow that characterizes LCPD.No one theory has been proven as the underlying or contributing cause(s) of LCPD and it is possible that different individuals may have a different underlying causes. More research is necessary to determine the complex interactions that ultimately bring about the disorder.In a handful of extremely rare familial instances, mutations in the COL2A1 gene have been linked to avascular necrosis of the head of the thigh bone in children.
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Affects of Legg Calvé Perthes Disease
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Legg-Calvé-Perthes disease affects males approximately four to five times as often as females (4-5:1). According to reports in the medical literature, when the disorder occurs sporadically, males are predominantly affected. However, in families with more than one affected member (kindreds), the disorder appears to occur relatively equally among males and females. Reported cases of LCPD include several individuals within multiple, multigenerational families.The disorder usually affects children between the ages of six and 10 years; however, associated symptoms and findings may become apparent as early as age two or as late as age 12. The incidence and prevalence of LCPD is unknown and estimates vary greatly from one country to another. The disorder is more common in Caucasians.
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Affects of Legg Calvé Perthes Disease. Legg-Calvé-Perthes disease affects males approximately four to five times as often as females (4-5:1). According to reports in the medical literature, when the disorder occurs sporadically, males are predominantly affected. However, in families with more than one affected member (kindreds), the disorder appears to occur relatively equally among males and females. Reported cases of LCPD include several individuals within multiple, multigenerational families.The disorder usually affects children between the ages of six and 10 years; however, associated symptoms and findings may become apparent as early as age two or as late as age 12. The incidence and prevalence of LCPD is unknown and estimates vary greatly from one country to another. The disorder is more common in Caucasians.
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Related disorders of Legg Calvé Perthes Disease
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Symptoms of the following disorder can be similar to those of Legg-Calvé-Perthes disease. Comparisons may be useful for a differential diagnosis:Multiple epiphyseal dysplasia (MED) is a rare inherited spectrum of disorders characterized by malformation (dysplasia) of the growing portion or head of the long bones (epiphyses). Affected individuals may have an abnormally short thighbone (femur), unusually short hands and fingers, mild short stature, a waddling gait, and/or pain in the hips and knees. In some cases, painful swelling and inflammation of certain joints (arthritis) may be present as early as five years of age. Most cases of multiple epiphyseal dysplasia are inherited as autosomal dominant traits; rare cases are inherited as autosomal recessive traits. (For more information on these disorders, choose “multiple epiphyseal dysplasia” as your search term in the Rare Disease Database.)There are numerous additional conditions that may have symptoms similar to those seen in LCPD including hip fracture, bone infection (osteomyelitis), hemophilia, juvenile rheumatoid arthritis, infection of the hip joint (pyogenic arthritis), slipped capital femoral epiphysis, and certain rare disorders such as pseudoachondroplasia, Meyers dysplasia, or spondyloepiphyseal dysplasia tarda. Certain tumors can also resemble the symptoms associated with LCPD.
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Related disorders of Legg Calvé Perthes Disease. Symptoms of the following disorder can be similar to those of Legg-Calvé-Perthes disease. Comparisons may be useful for a differential diagnosis:Multiple epiphyseal dysplasia (MED) is a rare inherited spectrum of disorders characterized by malformation (dysplasia) of the growing portion or head of the long bones (epiphyses). Affected individuals may have an abnormally short thighbone (femur), unusually short hands and fingers, mild short stature, a waddling gait, and/or pain in the hips and knees. In some cases, painful swelling and inflammation of certain joints (arthritis) may be present as early as five years of age. Most cases of multiple epiphyseal dysplasia are inherited as autosomal dominant traits; rare cases are inherited as autosomal recessive traits. (For more information on these disorders, choose “multiple epiphyseal dysplasia” as your search term in the Rare Disease Database.)There are numerous additional conditions that may have symptoms similar to those seen in LCPD including hip fracture, bone infection (osteomyelitis), hemophilia, juvenile rheumatoid arthritis, infection of the hip joint (pyogenic arthritis), slipped capital femoral epiphysis, and certain rare disorders such as pseudoachondroplasia, Meyers dysplasia, or spondyloepiphyseal dysplasia tarda. Certain tumors can also resemble the symptoms associated with LCPD.
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Diagnosis of Legg Calvé Perthes Disease
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In most children with Legg-Calvé-Perthes disease, the first sign is a limp with or without pain in the hip, knee, thigh, or groin. Ordinary x-rays (radiograms) are almost always diagnostic. The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests, such as magnetic resonance imaging (MRI), arthrography, scintigraphy, and/or sonography.During MRI, a magnetic field and radio waves are used to create cross-sectional images of the upper end of the thigh bone (capital femoral epiphysis) and may demonstrate abnormal development of the epiphyses. Arthrography, in which an opaque substance is injected into a joint before X-rays are taken, is especially helpful in showing the cartilage surface of the bone and its shape. The X-rays may help to determine the shape of the end of the bone where it joins (articulates) with the hip. Viability of the bone may be evaluated using a specialized technique known as bone scan. During a bone scan, the individual ingests a radioactive substance that will accumulate in the target area (e.g., bones). A specialized camera is then used to detect the levels of radioactivity present in these structures, producing an image of the targeted structure. In sonography, reflected sound waves create an image of certain tissues and body structures and may detect characteristic changes in the hip and femur, such as Caffey sign.
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Diagnosis of Legg Calvé Perthes Disease. In most children with Legg-Calvé-Perthes disease, the first sign is a limp with or without pain in the hip, knee, thigh, or groin. Ordinary x-rays (radiograms) are almost always diagnostic. The diagnosis may be confirmed by a thorough clinical evaluation, a detailed patient history, and/or a variety of specialized tests, such as magnetic resonance imaging (MRI), arthrography, scintigraphy, and/or sonography.During MRI, a magnetic field and radio waves are used to create cross-sectional images of the upper end of the thigh bone (capital femoral epiphysis) and may demonstrate abnormal development of the epiphyses. Arthrography, in which an opaque substance is injected into a joint before X-rays are taken, is especially helpful in showing the cartilage surface of the bone and its shape. The X-rays may help to determine the shape of the end of the bone where it joins (articulates) with the hip. Viability of the bone may be evaluated using a specialized technique known as bone scan. During a bone scan, the individual ingests a radioactive substance that will accumulate in the target area (e.g., bones). A specialized camera is then used to detect the levels of radioactivity present in these structures, producing an image of the targeted structure. In sonography, reflected sound waves create an image of certain tissues and body structures and may detect characteristic changes in the hip and femur, such as Caffey sign.
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Therapies of Legg Calvé Perthes Disease
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TreatmentThe treatment of Legg-Calvé-Perthes disease is directed toward the specific symptoms presented by each individual. Treatment varies with the severity of symptoms and may require the coordinated efforts of a team of specialists. Pediatricians usually refer patients to specialists who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); orthopedic surgeons, especially those that specialized in pediatrics; physical therapists; and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Degenerative bone changes associated with LCPD usually heal on their own without intervention (spontaneously). Affected children should be closely monitored so the progression of the disease may be evaluated to ensure the bone reforms properly. Physical therapy may be recommended to maintain a good range of motion of the joint. Radiologic studies (e.g., MRI, arthrography, and bone scan) may be used to assist in monitoring the progression of the disease.Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can be used for mild to moderate pain.In other cases, decreased physical activity, bedrest (if pain is present and prolonged) with or without traction, and/or stretching exercises (if stiffness occurs), particularly exercises in which the legs are rotated away from the body (abduction exercises), may be recommended to decrease pain in the hip and maintain proper mobility of the joint. In addition, as an affected child ages and regrowth of the epiphysis occurs, physicians must ensure that epiphyseal growth is contained within the cavity of the hip bone (acetabulum) where the thigh bone (femur) and hip normally meet (articulate).Nonsurgical treatment may include crutches or a special brace or cast to keep the ball of the joint completely within the socket (acetabulum) so that it will not deform while healing.Surgical treatments may include various procedures designed to place and keep the ball within the socket. Surgery is done mainly to improve and preserve the shape of the hip joint in order to prevent or reduce the chances of arthritis later during life. A femoral or pelvic osteotomy is often performed. Osteotomy is a surgical procedure in which bone is cut to shorten, lengthen, or change the alignment (i.e. reposition or reorient the bone). Some adults may ultimately require a total hip replacement surgery (total hip arthroplasty) later in life due to osteoarthritis.Physicians may rely upon specific classification systems to make certain decisions concerning treatment and predict an affected individual’s long-term progress. For example, the Stulberg Classification System, created in 1981, defines five outcome categories based upon the shape of the femoral head and its relationship with the hip socket (as seen upon x-ray imaging studies). However, the variability of the disease and long term follow up needed to understand the outcome of treatment have contributed to the lack of establishing a universal treatment strategy for children with this disorder.
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Therapies of Legg Calvé Perthes Disease. TreatmentThe treatment of Legg-Calvé-Perthes disease is directed toward the specific symptoms presented by each individual. Treatment varies with the severity of symptoms and may require the coordinated efforts of a team of specialists. Pediatricians usually refer patients to specialists who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); orthopedic surgeons, especially those that specialized in pediatrics; physical therapists; and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Degenerative bone changes associated with LCPD usually heal on their own without intervention (spontaneously). Affected children should be closely monitored so the progression of the disease may be evaluated to ensure the bone reforms properly. Physical therapy may be recommended to maintain a good range of motion of the joint. Radiologic studies (e.g., MRI, arthrography, and bone scan) may be used to assist in monitoring the progression of the disease.Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can be used for mild to moderate pain.In other cases, decreased physical activity, bedrest (if pain is present and prolonged) with or without traction, and/or stretching exercises (if stiffness occurs), particularly exercises in which the legs are rotated away from the body (abduction exercises), may be recommended to decrease pain in the hip and maintain proper mobility of the joint. In addition, as an affected child ages and regrowth of the epiphysis occurs, physicians must ensure that epiphyseal growth is contained within the cavity of the hip bone (acetabulum) where the thigh bone (femur) and hip normally meet (articulate).Nonsurgical treatment may include crutches or a special brace or cast to keep the ball of the joint completely within the socket (acetabulum) so that it will not deform while healing.Surgical treatments may include various procedures designed to place and keep the ball within the socket. Surgery is done mainly to improve and preserve the shape of the hip joint in order to prevent or reduce the chances of arthritis later during life. A femoral or pelvic osteotomy is often performed. Osteotomy is a surgical procedure in which bone is cut to shorten, lengthen, or change the alignment (i.e. reposition or reorient the bone). Some adults may ultimately require a total hip replacement surgery (total hip arthroplasty) later in life due to osteoarthritis.Physicians may rely upon specific classification systems to make certain decisions concerning treatment and predict an affected individual’s long-term progress. For example, the Stulberg Classification System, created in 1981, defines five outcome categories based upon the shape of the femoral head and its relationship with the hip socket (as seen upon x-ray imaging studies). However, the variability of the disease and long term follow up needed to understand the outcome of treatment have contributed to the lack of establishing a universal treatment strategy for children with this disorder.
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Overview of Legionnaires’ Disease
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Legionnaires’ disease, caused by the aerobic gram-negative coccobacillus Legionella, mostly L. pneumophila, is an important cause of community-acquired pneumonia (CAP), accounting for approximatively 10% of cases. The exact incidence of Legionnaires’ disease is unknown due to different awareness levels in different countries, diagnostic methods and reporting, but the US Centers for Disease control (CDC) reported nearly 10,000 cases in the USA in 2018. Infection with Legionella occurs through the inhalation of an aerosol containing bacteria generated by water droplets, usually coming from a contaminated water system. It does not spread from person-to-person. Legionnaires’ disease often affects individuals over the age of 50, people who are heavy smokers and immunocompromised individuals. Legionnaires’ disease presents similarly to other bacterial pneumonias, such as pneumococcal pneumonia, with signs and symptoms like high fever, cough, chills, difficulty breathing (dyspnea), headache, chest pain, muscle pain (myalgia) or joint pain (arthralgia). Legionnaires’ disease can present as a more severe illness in some patients, mostly in those who are immunocompromised, and might require hospitalization and intensive care. This disease is treated with an antibiotic monotherapy, which is the use of only one antibiotic, with azithromycin or levofloxacin on an outpatient basis. Legionella pneumonia has a fatality rate of 10% in the community or 25% if healthcare-associated, which is similar to other types of bacterial pneumonia.IntroductionLegionnaires’ disease was initially recognized in early 1977, when an outbreak of a form of pneumonia affected members attending an American Legion Convention at a hotel in Philadelphia in 1976. The bacterium responsible for the disease was identified and named Legionella pneumophila by the CDC. They were later able to identify outbreaks and sporadic cases of this disease dating back to the 1940s, but the causative agent could not be identified at the time because Legionella pneumophila does not grow on traditional culture media.
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Overview of Legionnaires’ Disease. Legionnaires’ disease, caused by the aerobic gram-negative coccobacillus Legionella, mostly L. pneumophila, is an important cause of community-acquired pneumonia (CAP), accounting for approximatively 10% of cases. The exact incidence of Legionnaires’ disease is unknown due to different awareness levels in different countries, diagnostic methods and reporting, but the US Centers for Disease control (CDC) reported nearly 10,000 cases in the USA in 2018. Infection with Legionella occurs through the inhalation of an aerosol containing bacteria generated by water droplets, usually coming from a contaminated water system. It does not spread from person-to-person. Legionnaires’ disease often affects individuals over the age of 50, people who are heavy smokers and immunocompromised individuals. Legionnaires’ disease presents similarly to other bacterial pneumonias, such as pneumococcal pneumonia, with signs and symptoms like high fever, cough, chills, difficulty breathing (dyspnea), headache, chest pain, muscle pain (myalgia) or joint pain (arthralgia). Legionnaires’ disease can present as a more severe illness in some patients, mostly in those who are immunocompromised, and might require hospitalization and intensive care. This disease is treated with an antibiotic monotherapy, which is the use of only one antibiotic, with azithromycin or levofloxacin on an outpatient basis. Legionella pneumonia has a fatality rate of 10% in the community or 25% if healthcare-associated, which is similar to other types of bacterial pneumonia.IntroductionLegionnaires’ disease was initially recognized in early 1977, when an outbreak of a form of pneumonia affected members attending an American Legion Convention at a hotel in Philadelphia in 1976. The bacterium responsible for the disease was identified and named Legionella pneumophila by the CDC. They were later able to identify outbreaks and sporadic cases of this disease dating back to the 1940s, but the causative agent could not be identified at the time because Legionella pneumophila does not grow on traditional culture media.
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Symptoms of Legionnaires’ Disease
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Legionnaires’ disease is a respiratory disease, which means it affects the lungs. The lungs are composed of lobes, two for the left and three for the right lung. The air travels in the lungs through the bronchi, then bronchioles and then into alveoli, which are little sacs forming lung tissue. Pneumonia is an inflammation of the lungs caused by an infection, where the alveoli fill with pus and can eventually become solid (consolidation). The incubation period for Legionnaires’ disease, which is the time between exposure to the infectious agent and the onset of symptoms, is two to 10 days. Longer incubation periods have been recorded in a minority of cases, for example in immunocompromised patients. The prodrome of symptoms, which are the early signs of illness, include headache, muscle pain (myalgia), weakness and fatigue (asthenia) and loss of appetite (anorexia). The most common signs and symptoms are a high fever up to more than 40oC (104oF), which can be accompanied by a slow heart rate (relative bradycardia); cough, which is productive of purulent sputum in approximately 50% of patients; difficulty breathing (dyspnea); neurological abnormalities such as confusion, delirium and lethargy; muscle or joint pain (myalgia or arthralgia); diarrhea; chest pain, which is often worse on inspiration (pleuritic) and on the side affected by the pneumonia; headache; and, nausea or vomiting. A small proportion of affected individuals can show non-respiratory manifestations such as an enlarged spleen (splenomegaly) or spleen rupture; inflammation of the pericardium, which is the bag around the heart (pericarditis); inflammation of the heart muscle (myocarditis); joint inflammation (arthritis); acute renal failure; wound infections; and, infections of the central nervous system. Laboratory findings may include low blood sodium (hyponatremia), low blood phosphorus (hypophosphatemia), abnormal liver function tests, elevated creatine kinase, high C-reactive protein levels and blood in the urine (microscopic hematuria). These findings are common but are non-specific to Legionnaires’ disease. Radiographic finding on a chest X-Ray include pulmonary infiltrates, which are usually patchy and affecting only one lobe (unilobar) and progressing to consolidation of the surrounding lung tissue. However, there is no specific radiographic features suggestive of Legionnaires’ disease, and all the types of infiltrates have been reported in Legionnaires’ disease cases.
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Symptoms of Legionnaires’ Disease. Legionnaires’ disease is a respiratory disease, which means it affects the lungs. The lungs are composed of lobes, two for the left and three for the right lung. The air travels in the lungs through the bronchi, then bronchioles and then into alveoli, which are little sacs forming lung tissue. Pneumonia is an inflammation of the lungs caused by an infection, where the alveoli fill with pus and can eventually become solid (consolidation). The incubation period for Legionnaires’ disease, which is the time between exposure to the infectious agent and the onset of symptoms, is two to 10 days. Longer incubation periods have been recorded in a minority of cases, for example in immunocompromised patients. The prodrome of symptoms, which are the early signs of illness, include headache, muscle pain (myalgia), weakness and fatigue (asthenia) and loss of appetite (anorexia). The most common signs and symptoms are a high fever up to more than 40oC (104oF), which can be accompanied by a slow heart rate (relative bradycardia); cough, which is productive of purulent sputum in approximately 50% of patients; difficulty breathing (dyspnea); neurological abnormalities such as confusion, delirium and lethargy; muscle or joint pain (myalgia or arthralgia); diarrhea; chest pain, which is often worse on inspiration (pleuritic) and on the side affected by the pneumonia; headache; and, nausea or vomiting. A small proportion of affected individuals can show non-respiratory manifestations such as an enlarged spleen (splenomegaly) or spleen rupture; inflammation of the pericardium, which is the bag around the heart (pericarditis); inflammation of the heart muscle (myocarditis); joint inflammation (arthritis); acute renal failure; wound infections; and, infections of the central nervous system. Laboratory findings may include low blood sodium (hyponatremia), low blood phosphorus (hypophosphatemia), abnormal liver function tests, elevated creatine kinase, high C-reactive protein levels and blood in the urine (microscopic hematuria). These findings are common but are non-specific to Legionnaires’ disease. Radiographic finding on a chest X-Ray include pulmonary infiltrates, which are usually patchy and affecting only one lobe (unilobar) and progressing to consolidation of the surrounding lung tissue. However, there is no specific radiographic features suggestive of Legionnaires’ disease, and all the types of infiltrates have been reported in Legionnaires’ disease cases.
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Causes of Legionnaires’ Disease
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Legionellosis refers to disease caused by an infection with bacteria of the Legionella family, which includes 59 known species, from which 26 are known to cause disease in humans. These bacteria are gram-negative coccobacilli. The most common agent reported to cause Legionnaires’ disease is Legionella pneumophila serogroup 1. Legionella bacteria are found in aquatic environments, both natural and artificial. They can be found in water with temperatures ranging from below 0oC to up to 60oC, but are mostly found in hot water services, such as evaporative cooling water systems that serve air conditioning plants or hot tubs. Bacterial growth occurs most in stagnant water with temperatures between 20-45oC, with the optimal temperature for multiplication being between 32-42oC. Some species, such as L. longbeachae, are associated with soil exposure. Legionella species are intracellular organisms, which means they cannot grow by themselves; they need the support of other organisms (usually protozoa) to multiply. Due to the bacteria growing inside protozoa and being a part of a biofilm, which is slime made by microorganisms, Legionella bacteria are protected from normal water treatment processes. Thus, Legionella bacteria can spread through towns in the drinking water system. The source of an outbreak can often be linked to either air conditioning or water systems, since Legionnaires’ disease is caused by the inhalation of contaminated water droplets.
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Causes of Legionnaires’ Disease. Legionellosis refers to disease caused by an infection with bacteria of the Legionella family, which includes 59 known species, from which 26 are known to cause disease in humans. These bacteria are gram-negative coccobacilli. The most common agent reported to cause Legionnaires’ disease is Legionella pneumophila serogroup 1. Legionella bacteria are found in aquatic environments, both natural and artificial. They can be found in water with temperatures ranging from below 0oC to up to 60oC, but are mostly found in hot water services, such as evaporative cooling water systems that serve air conditioning plants or hot tubs. Bacterial growth occurs most in stagnant water with temperatures between 20-45oC, with the optimal temperature for multiplication being between 32-42oC. Some species, such as L. longbeachae, are associated with soil exposure. Legionella species are intracellular organisms, which means they cannot grow by themselves; they need the support of other organisms (usually protozoa) to multiply. Due to the bacteria growing inside protozoa and being a part of a biofilm, which is slime made by microorganisms, Legionella bacteria are protected from normal water treatment processes. Thus, Legionella bacteria can spread through towns in the drinking water system. The source of an outbreak can often be linked to either air conditioning or water systems, since Legionnaires’ disease is caused by the inhalation of contaminated water droplets.
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Affects of Legionnaires’ Disease
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The incidence of Legionnaires’ disease in the USA was estimated to be 10,000 cases in 2018. There is seasonal variation as most patients are diagnosed in the summer and early autumn. Studies show that most cases were community-acquired pneumonia (CAP) while about a quarter of the cases were travelled-related and less than 10% were health-care-related. However, it is hard to get an accurate estimate of the incidence of this disease since it is underdiagnosed, underreported and it has been shown that some people will develop only mild illness or show no symptoms at all. This disease mostly affects people over the age of 50, children rarely getting sick with it. Studies also show that men are more at risk than women to develop Legionnaires’ disease, with a ratio of 3:1. Some risk factors increase the incidence of this disease in specific populations, including: cigarette smoking, heavy alcohol consumption, diabetes, chronic respiratory disease, chronic kidney disease and immunosuppression due to cancer or organ transplantation. Hospitalized patients can be at an increased risk of contracting Legionnaires’ disease in certain situations such as after an organ transplant, after receiving general anesthesia because of the increased risk of aspiration or use of immunosuppressant drugs.
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Affects of Legionnaires’ Disease. The incidence of Legionnaires’ disease in the USA was estimated to be 10,000 cases in 2018. There is seasonal variation as most patients are diagnosed in the summer and early autumn. Studies show that most cases were community-acquired pneumonia (CAP) while about a quarter of the cases were travelled-related and less than 10% were health-care-related. However, it is hard to get an accurate estimate of the incidence of this disease since it is underdiagnosed, underreported and it has been shown that some people will develop only mild illness or show no symptoms at all. This disease mostly affects people over the age of 50, children rarely getting sick with it. Studies also show that men are more at risk than women to develop Legionnaires’ disease, with a ratio of 3:1. Some risk factors increase the incidence of this disease in specific populations, including: cigarette smoking, heavy alcohol consumption, diabetes, chronic respiratory disease, chronic kidney disease and immunosuppression due to cancer or organ transplantation. Hospitalized patients can be at an increased risk of contracting Legionnaires’ disease in certain situations such as after an organ transplant, after receiving general anesthesia because of the increased risk of aspiration or use of immunosuppressant drugs.
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Related disorders of Legionnaires’ Disease
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Like Legionnaires’ disease, Pontiac fever is also caused by exposure to bacteria from the Legionella family. Its symptoms usually include malaise, fever, headache, chills, muscle pain (myalgia), nausea, vomiting and diarrhea. The characteristic symptoms of pneumonia from Legionnaires’ disease are absent in Pontiac fever. The incubation period for Pontiac fever is one to two days, compared to two to 10 days in Legionnaires’ disease. Individuals affected by Pontiac fever usually do not require any treatment, as the illness is self-limited. Patients usually recover in one to eight days (median of four days) with no residual ill effects. Diagnostic tests are not usually performed on patients with Pontiac fever as there is no agreed-upon definition, specific findings or specific laboratory test to diagnose it. Therefore, clinical suspicion should be based on possible exposures, however, individuals with Pontiac fever can test positive with a urinary antigen test, which is discussed in the ‘’Diagnosis’’ section below. Pontiac fever does not affect specific groups more or less than others, unlike Legionnaires’ disease. The differential diagnosis for Legionnaires’ disease should include other types of bacterial pneumonia, especially pneumococcal pneumonia. A failure to respond to beta-lactam therapy in patients with pneumonia can be indicative of an infection with Legionella spp. Also, presence of gastrointestinal and neurological symptoms in a patient with pneumonia suggests Legionnaires’ disease in comparison to other bacterial pneumonia.
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Related disorders of Legionnaires’ Disease. Like Legionnaires’ disease, Pontiac fever is also caused by exposure to bacteria from the Legionella family. Its symptoms usually include malaise, fever, headache, chills, muscle pain (myalgia), nausea, vomiting and diarrhea. The characteristic symptoms of pneumonia from Legionnaires’ disease are absent in Pontiac fever. The incubation period for Pontiac fever is one to two days, compared to two to 10 days in Legionnaires’ disease. Individuals affected by Pontiac fever usually do not require any treatment, as the illness is self-limited. Patients usually recover in one to eight days (median of four days) with no residual ill effects. Diagnostic tests are not usually performed on patients with Pontiac fever as there is no agreed-upon definition, specific findings or specific laboratory test to diagnose it. Therefore, clinical suspicion should be based on possible exposures, however, individuals with Pontiac fever can test positive with a urinary antigen test, which is discussed in the ‘’Diagnosis’’ section below. Pontiac fever does not affect specific groups more or less than others, unlike Legionnaires’ disease. The differential diagnosis for Legionnaires’ disease should include other types of bacterial pneumonia, especially pneumococcal pneumonia. A failure to respond to beta-lactam therapy in patients with pneumonia can be indicative of an infection with Legionella spp. Also, presence of gastrointestinal and neurological symptoms in a patient with pneumonia suggests Legionnaires’ disease in comparison to other bacterial pneumonia.
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Diagnosis of Legionnaires’ Disease
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As mentioned above, a failure to respond to beta-lactam antibiotics or the appearance of gastrointestinal and neurological symptoms in pneumonia patients should raise suspicions about an infection with Legionella. Legionnaires’ disease can be diagnosed with different laboratory tests such as PCR, cultures and a urinary antigen test. Legionella bacteria are very hard to detect on gram-stain so this is not the diagnostic method of choice in the case of Legionella pneumophila pneumonia. Blood tests can also be done to detect the presence of specific antibodies in the serum, but they are not a reliable diagnostic method as it takes several weeks for antibodies to appear in the blood and a positive result could be from a previous Legionella subclinical infection. The best method for diagnosis is a polymerase chain reaction (PCR) test. In a PCR test, the genetic material (DNA) can be amplified and identified more easily. The advantage of the PCR is that it can detect all the species and serogroups from the Legionella family and is a rapid test, but its availability can be limited. PCR testing is the test with the highest sensitivity and specificity for the diagnosis of Legionnaires’ disease.Other diagnostic tests for Legionnaires’ disease are a combination of respiratory sample culture and urinary antigen test. Legionella can be isolated by culture from a lower respiratory tract sample, lung tissue or pleural fluid. It usually takes three to five days to get the results from a culture. Cultures can detect Legionella species and serogroups that cannot be detected by the urinary antigen test, which only detects Legionella pneumophila serogroup 1. It is important to note that while a positive culture is diagnostic of Legionnaires’ disease, a negative culture does not rule out the disease due to the poor sensitivity of the test. Cultures from blood yield poor results and should not be performed.The urinary antigen test consists of looking for “pieces” (antigens) of Legionella in the urine. The antigens can be detected, and a positive test can be reported within 48 to 72 hours from the onset of the symptoms and remain positive for approximately two months. As mentioned, the limitation of the urinary antigen test is that it only detects Legionella pneumophila serovar 1. Since this serogroup represents at least 80% of the cases of Legionnaires’ disease in the USA, this is still the most widely used test. If Legionnaires’ disease is suspected after a negative urinary antigen test, a respiratory sample should be sent for PCR or culture to confirm the diagnosis.
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Diagnosis of Legionnaires’ Disease. As mentioned above, a failure to respond to beta-lactam antibiotics or the appearance of gastrointestinal and neurological symptoms in pneumonia patients should raise suspicions about an infection with Legionella. Legionnaires’ disease can be diagnosed with different laboratory tests such as PCR, cultures and a urinary antigen test. Legionella bacteria are very hard to detect on gram-stain so this is not the diagnostic method of choice in the case of Legionella pneumophila pneumonia. Blood tests can also be done to detect the presence of specific antibodies in the serum, but they are not a reliable diagnostic method as it takes several weeks for antibodies to appear in the blood and a positive result could be from a previous Legionella subclinical infection. The best method for diagnosis is a polymerase chain reaction (PCR) test. In a PCR test, the genetic material (DNA) can be amplified and identified more easily. The advantage of the PCR is that it can detect all the species and serogroups from the Legionella family and is a rapid test, but its availability can be limited. PCR testing is the test with the highest sensitivity and specificity for the diagnosis of Legionnaires’ disease.Other diagnostic tests for Legionnaires’ disease are a combination of respiratory sample culture and urinary antigen test. Legionella can be isolated by culture from a lower respiratory tract sample, lung tissue or pleural fluid. It usually takes three to five days to get the results from a culture. Cultures can detect Legionella species and serogroups that cannot be detected by the urinary antigen test, which only detects Legionella pneumophila serogroup 1. It is important to note that while a positive culture is diagnostic of Legionnaires’ disease, a negative culture does not rule out the disease due to the poor sensitivity of the test. Cultures from blood yield poor results and should not be performed.The urinary antigen test consists of looking for “pieces” (antigens) of Legionella in the urine. The antigens can be detected, and a positive test can be reported within 48 to 72 hours from the onset of the symptoms and remain positive for approximately two months. As mentioned, the limitation of the urinary antigen test is that it only detects Legionella pneumophila serovar 1. Since this serogroup represents at least 80% of the cases of Legionnaires’ disease in the USA, this is still the most widely used test. If Legionnaires’ disease is suspected after a negative urinary antigen test, a respiratory sample should be sent for PCR or culture to confirm the diagnosis.
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Therapies of Legionnaires’ Disease
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TreatmentStudies show that early therapy can reduce mortality. Legionnaires’ disease is treated effectively by many classes of antibiotics: macrolides, tetracyclines, ketolides and quinolones. The first line of treatment is a course of azithromycin, doxycycline or levofloxacin on an outpatient basis. Erythromycin is no longer used as first-line treatment as the newer macrolides and quinolones have a better activity against Legionella bacteria. In individuals with more severe disease who require hospitalization, the use of intravenous fluoroquinolones is recommended. In transplant patients, quinolones, doxycycline and azithromycin should be favored to avoid interactions with other drugs. Drug resistance has not been linked to treatment failure in cases of Legionella infections. There is no evidence supporting combined therapy, thus monotherapy is the mainstay of treatment.
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Therapies of Legionnaires’ Disease. TreatmentStudies show that early therapy can reduce mortality. Legionnaires’ disease is treated effectively by many classes of antibiotics: macrolides, tetracyclines, ketolides and quinolones. The first line of treatment is a course of azithromycin, doxycycline or levofloxacin on an outpatient basis. Erythromycin is no longer used as first-line treatment as the newer macrolides and quinolones have a better activity against Legionella bacteria. In individuals with more severe disease who require hospitalization, the use of intravenous fluoroquinolones is recommended. In transplant patients, quinolones, doxycycline and azithromycin should be favored to avoid interactions with other drugs. Drug resistance has not been linked to treatment failure in cases of Legionella infections. There is no evidence supporting combined therapy, thus monotherapy is the mainstay of treatment.
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Overview of Leigh Syndrome
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Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh syndrome usually begin between the ages of three months and two years, but some patients do not exhibit signs and symptoms until several years later. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. As Leigh syndrome progresses, symptoms may also include generalized weakness, lack of muscle tone (hypotonia), and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. Several different genetically determined enzyme defects can cause the syndrome, initially described over 60 years ago. Most individuals with Leigh syndrome have defects of mitochondrial energy production, such as deficiency of an enzyme of the mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex. In most cases, Leigh syndrome is inherited as an autosomal recessive trait. However, X-linked recessive and maternal inheritance, due to a mitochondrial DNA mutation, are additional modes of transmission.
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Overview of Leigh Syndrome. Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and optic nerve). The symptoms of Leigh syndrome usually begin between the ages of three months and two years, but some patients do not exhibit signs and symptoms until several years later. Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, irritability, and/or seizure activity. As Leigh syndrome progresses, symptoms may also include generalized weakness, lack of muscle tone (hypotonia), and episodes of lactic acidosis, which may lead to impairment of respiratory and kidney function. Several different genetically determined enzyme defects can cause the syndrome, initially described over 60 years ago. Most individuals with Leigh syndrome have defects of mitochondrial energy production, such as deficiency of an enzyme of the mitochondrial respiratory chain complex or the pyruvate dehydrogenase complex. In most cases, Leigh syndrome is inherited as an autosomal recessive trait. However, X-linked recessive and maternal inheritance, due to a mitochondrial DNA mutation, are additional modes of transmission.
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Leigh Syndrome
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Symptoms of Leigh Syndrome
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The symptoms of classical Leigh syndrome (infantile necrotizing encephalopathy), a rapidly progressive neurological disorder, usually begin between the ages of 3 months and 2 years. In most children, the first noticeable sign is the loss of previously acquired motor skills. When there is early onset (i.e., 3 months), loss of head control and poor sucking ability may be the first noticeable symptoms. This may be accompanied by a profound loss of appetite, recurrent vomiting, irritability, continuous crying and possible seizure activity. Delays in reaching developmental milestones may also occur. Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).If the onset of Leigh syndrome is later in childhood (e.g., 24 months), a child may experience difficulty articulating words (dysarthria) and coordinating voluntary movements such as walking or running (ataxia). Previously acquired intellectual skills may diminish and intellectual disability may also occur.Progressive neurological deterioration associated with Leigh syndrome is marked by a variety of symptoms including generalized weakness, lack of muscle tone (hypotonia), clumsiness, tremors, muscle spasms (spasticity) that result in slow, stiff movements of the legs, and/or the absence of tendon reflexes. Further neurological development is delayed.Episodes of lactic acidosis may occur and are characterized by abnormally high levels of lactic acid in the blood, brain and other tissues of the body. Periodically, levels of carbon dioxide in the blood may also be abnormally elevated (hypercapnia). Lactic acidosis and hypercapnia can lead to psychomotor regression and respiratory, heart, or kidney impairment.Children with Leigh syndrome usually develop respiratory problems including the temporary cessation of spontaneous breathing (apnea), difficulty breathing (dyspnea), abnormally rapid breathing (hyperventilation), and/or abnormal breathing patterns (Cheyne-Stokes). Some infants may also experience difficulty swallowing (dysphagia). Visual problems may include abnormally rapid eye movements (nystagmus), sluggish pupils, crossed eyes (strabismus), paralysis of certain eye muscles (ophthalmoplegia), deterioration of the nerves of the eyes (optic atrophy), and/or visual impairment leading to blindness.Leigh syndrome may also affect the heart. Some children with this disorder may have abnormal enlargement of the heart (hypertrophic cardiomyopathy) and overgrowth of the fibrous membrane that divides the various chambers of the heart (asymmetric septal hypertrophy). Disease affecting the nerves outside of the central nervous system (peripheral neuropathy) may eventually occur, causing progressive weakness of the arms and legs.The symptoms of the X-linked infantile form of Leigh syndrome are similar to those of classical Leigh syndrome. The symptoms of the adult-onset form of Leigh syndrome (subacute necrotizing encephalomyelopathy), a very rare form of the disorder, generally begin during adolescence or early adulthood. Initial symptoms are generally related to vision and may include such abnormalities as blurred “filmy” central visual fields (central scotoma), colorblindness, and/or progressive visual loss due to degeneration of the optic nerve (bilateral optic atrophy). The neurological problems associated with the disease progress slowly in this form of the disorder. At about 50 years of age, affected individuals may find it progressively difficult to coordinate voluntary movements (ataxia). Additional late symptoms may include partial paralysis and involuntary muscle movements (spastic paresis), sudden muscle spasms (clonic jerks), grand mal seizures, and/or varying degrees of dementia.
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Symptoms of Leigh Syndrome. The symptoms of classical Leigh syndrome (infantile necrotizing encephalopathy), a rapidly progressive neurological disorder, usually begin between the ages of 3 months and 2 years. In most children, the first noticeable sign is the loss of previously acquired motor skills. When there is early onset (i.e., 3 months), loss of head control and poor sucking ability may be the first noticeable symptoms. This may be accompanied by a profound loss of appetite, recurrent vomiting, irritability, continuous crying and possible seizure activity. Delays in reaching developmental milestones may also occur. Affected infants may fail to grow and gain weight at the expected rate (failure to thrive).If the onset of Leigh syndrome is later in childhood (e.g., 24 months), a child may experience difficulty articulating words (dysarthria) and coordinating voluntary movements such as walking or running (ataxia). Previously acquired intellectual skills may diminish and intellectual disability may also occur.Progressive neurological deterioration associated with Leigh syndrome is marked by a variety of symptoms including generalized weakness, lack of muscle tone (hypotonia), clumsiness, tremors, muscle spasms (spasticity) that result in slow, stiff movements of the legs, and/or the absence of tendon reflexes. Further neurological development is delayed.Episodes of lactic acidosis may occur and are characterized by abnormally high levels of lactic acid in the blood, brain and other tissues of the body. Periodically, levels of carbon dioxide in the blood may also be abnormally elevated (hypercapnia). Lactic acidosis and hypercapnia can lead to psychomotor regression and respiratory, heart, or kidney impairment.Children with Leigh syndrome usually develop respiratory problems including the temporary cessation of spontaneous breathing (apnea), difficulty breathing (dyspnea), abnormally rapid breathing (hyperventilation), and/or abnormal breathing patterns (Cheyne-Stokes). Some infants may also experience difficulty swallowing (dysphagia). Visual problems may include abnormally rapid eye movements (nystagmus), sluggish pupils, crossed eyes (strabismus), paralysis of certain eye muscles (ophthalmoplegia), deterioration of the nerves of the eyes (optic atrophy), and/or visual impairment leading to blindness.Leigh syndrome may also affect the heart. Some children with this disorder may have abnormal enlargement of the heart (hypertrophic cardiomyopathy) and overgrowth of the fibrous membrane that divides the various chambers of the heart (asymmetric septal hypertrophy). Disease affecting the nerves outside of the central nervous system (peripheral neuropathy) may eventually occur, causing progressive weakness of the arms and legs.The symptoms of the X-linked infantile form of Leigh syndrome are similar to those of classical Leigh syndrome. The symptoms of the adult-onset form of Leigh syndrome (subacute necrotizing encephalomyelopathy), a very rare form of the disorder, generally begin during adolescence or early adulthood. Initial symptoms are generally related to vision and may include such abnormalities as blurred “filmy” central visual fields (central scotoma), colorblindness, and/or progressive visual loss due to degeneration of the optic nerve (bilateral optic atrophy). The neurological problems associated with the disease progress slowly in this form of the disorder. At about 50 years of age, affected individuals may find it progressively difficult to coordinate voluntary movements (ataxia). Additional late symptoms may include partial paralysis and involuntary muscle movements (spastic paresis), sudden muscle spasms (clonic jerks), grand mal seizures, and/or varying degrees of dementia.
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Leigh Syndrome
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Causes of Leigh Syndrome
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Several different types of genetically determined metabolic defects can lead to Leigh syndrome. The condition may be caused by a deficiency of one or a number of different enzymes (e.g., mitochondrial respiratory chain enzymes or enzyme components of the pyruvate dehydrogenase complex). These enzyme deficiencies are caused by changes (mutations) in one of several different disease genes (genetic heterogeneity). These mutations may be inherited as an autosomal recessive trait, an X-linked recessive trait, or as a mutation found within the DNA of mitochondria. In some cases of Leigh syndrome, no genetic cause can be identified.Genetic information is contained in two types of DNA: nuclear DNA (nDNA) is contained in the nucleus of a cell and is inherited from both biological parents. Mitochondrial DNA (mtDNA) is contained in the mitochondria of cells and is inherited exclusively from the child’s mother. Genetic diseases due to nDNA mutations (change in genetic material), 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 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent.Other nDNA-based enzyme deficiencies (i.e., NADH-CoQ and cytochrome C oxidase) have also been implicated as a cause of some cases of autosomal recessive Leigh syndrome. These specific enzyme deficiencies have been linked to several different genes. For example, mutations of the SURF1 gene located on chromosome 9 causes Leigh syndrome associated with cytochrome C oxidase deficiency. All of these different genetic defects seem to have a common effect on the central nervous system, resulting in progressive neurological deterioration.There is also evidence in the medical literature for a nDNA X-linked recessive form of Leigh syndrome. This form of the disease has been linked to a specific defect in a gene known as E1-alpha subunit of the pyruvate dehydrogenase complex that is located on the short arm (p) of the X chromosome (Xp22.2-22.1). X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.In some cases, Leigh syndrome may be inherited from the mother as a mutation found within the DNA of mitochondria. Mitochondria, found by the hundreds or thousands within almost every cell of the body, regulate the production of cellular energy and carry the genetic blueprints for this process within their own unique DNA (mtDNA). The mtDNA from the father is carried by sperm cells. However, during the process of fertilization, the father’s mtDNA is lost. As a result, all human mtDNA comes from the mother. An affected mother will pass the traits to all of her children, but only the daughters will pass the mutation(s) onto the next generation.The genetic mutations that are present in the mtDNA may outnumber the normal copies of the genes. Symptoms may not occur until mutations are present in a significant percentage of the mitochondria. The uneven distribution of normal and mutant mtDNA in different tissues of the body can affect different organ systems in individuals from the same family and can result in a variety of symptoms in affected family members.
The specific mtDNA defect that may be responsible for some cases of Leigh syndrome (mtDNA nt 8993) is associated with a gene known as ATPase 6 (complex V deficiency of the mitochondrial respiratory chain [ATPase deficiency]). These cases are sometimes referred to as maternally inherited Leigh syndrome (MILS) or mtDNA-associated Leigh syndrome.Some researchers believe that cases of adult-onset Leigh syndrome may be inherited as an autosomal dominant trait, due to a nDNA mutation. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. Because the condition is due to a nDNA mutation, the abnormal gene can be inherited from either parent, or can be the result of a new nDNA mutation in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
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Causes of Leigh Syndrome. Several different types of genetically determined metabolic defects can lead to Leigh syndrome. The condition may be caused by a deficiency of one or a number of different enzymes (e.g., mitochondrial respiratory chain enzymes or enzyme components of the pyruvate dehydrogenase complex). These enzyme deficiencies are caused by changes (mutations) in one of several different disease genes (genetic heterogeneity). These mutations may be inherited as an autosomal recessive trait, an X-linked recessive trait, or as a mutation found within the DNA of mitochondria. In some cases of Leigh syndrome, no genetic cause can be identified.Genetic information is contained in two types of DNA: nuclear DNA (nDNA) is contained in the nucleus of a cell and is inherited from both biological parents. Mitochondrial DNA (mtDNA) is contained in the mitochondria of cells and is inherited exclusively from the child’s mother. Genetic diseases due to nDNA mutations (change in genetic material), 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 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent.Other nDNA-based enzyme deficiencies (i.e., NADH-CoQ and cytochrome C oxidase) have also been implicated as a cause of some cases of autosomal recessive Leigh syndrome. These specific enzyme deficiencies have been linked to several different genes. For example, mutations of the SURF1 gene located on chromosome 9 causes Leigh syndrome associated with cytochrome C oxidase deficiency. All of these different genetic defects seem to have a common effect on the central nervous system, resulting in progressive neurological deterioration.There is also evidence in the medical literature for a nDNA X-linked recessive form of Leigh syndrome. This form of the disease has been linked to a specific defect in a gene known as E1-alpha subunit of the pyruvate dehydrogenase complex that is located on the short arm (p) of the X chromosome (Xp22.2-22.1). X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.In some cases, Leigh syndrome may be inherited from the mother as a mutation found within the DNA of mitochondria. Mitochondria, found by the hundreds or thousands within almost every cell of the body, regulate the production of cellular energy and carry the genetic blueprints for this process within their own unique DNA (mtDNA). The mtDNA from the father is carried by sperm cells. However, during the process of fertilization, the father’s mtDNA is lost. As a result, all human mtDNA comes from the mother. An affected mother will pass the traits to all of her children, but only the daughters will pass the mutation(s) onto the next generation.The genetic mutations that are present in the mtDNA may outnumber the normal copies of the genes. Symptoms may not occur until mutations are present in a significant percentage of the mitochondria. The uneven distribution of normal and mutant mtDNA in different tissues of the body can affect different organ systems in individuals from the same family and can result in a variety of symptoms in affected family members.
The specific mtDNA defect that may be responsible for some cases of Leigh syndrome (mtDNA nt 8993) is associated with a gene known as ATPase 6 (complex V deficiency of the mitochondrial respiratory chain [ATPase deficiency]). These cases are sometimes referred to as maternally inherited Leigh syndrome (MILS) or mtDNA-associated Leigh syndrome.Some researchers believe that cases of adult-onset Leigh syndrome may be inherited as an autosomal dominant trait, due to a nDNA mutation. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. Because the condition is due to a nDNA mutation, the abnormal gene can be inherited from either parent, or can be the result of a new nDNA mutation in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
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Leigh Syndrome
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Affects of Leigh Syndrome
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The classical form of Leigh syndrome develops during infancy (infantile necrotizing encephalopathy) and usually begins between the ages of 3 months and 2 years. This form of the disease affects males and females in equal numbers.In cases of Leigh syndrome that are inherited as an X-linked recessive trait, the symptoms typically develop during infancy. Almost twice as many males as females are affected by this form of the disease.In some rare cases, Leigh syndrome may begin during late adolescence or early adulthood (adult-onset subacute necrotizing encephalomyelopathy). In these cases, which affect twice as many males as females, the progression of the disease is slower than the classical form of the disease.Researchers once believed that the classical form of Leigh syndrome accounted for approximately 80 percent of cases. In the medical literature, the prevalence of Leigh syndrome has been estimated at 1 in 36,000-40,000 live births.
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Affects of Leigh Syndrome. The classical form of Leigh syndrome develops during infancy (infantile necrotizing encephalopathy) and usually begins between the ages of 3 months and 2 years. This form of the disease affects males and females in equal numbers.In cases of Leigh syndrome that are inherited as an X-linked recessive trait, the symptoms typically develop during infancy. Almost twice as many males as females are affected by this form of the disease.In some rare cases, Leigh syndrome may begin during late adolescence or early adulthood (adult-onset subacute necrotizing encephalomyelopathy). In these cases, which affect twice as many males as females, the progression of the disease is slower than the classical form of the disease.Researchers once believed that the classical form of Leigh syndrome accounted for approximately 80 percent of cases. In the medical literature, the prevalence of Leigh syndrome has been estimated at 1 in 36,000-40,000 live births.
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Leigh Syndrome
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Related disorders of Leigh Syndrome
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Symptoms of the following disorders can be similar to those of Leigh syndrome. Comparisons may be useful for a differential diagnosis:Wernicke syndrome and Korsakoff syndrome are related disorders that often occur due to a deficiency of thiamine (vitamin B1). Wernicke’s syndrome, also known as Wernicke encephalopathy, is a neurological disease characterized by the clinical triad of confusion, the inability to coordinate voluntary movement (ataxia), and eye (ocular) abnormalities. Korsakoff’s syndrome is a neurological disorder characterized by disproportionate memory loss in relation to other mental aspects. When these two disorders occur together, the term Wernicke-Korsakoff syndrome is used. In the United States, most cases occur in alcoholics. Some researchers believe Wernicke and Korsakoff syndromes are separate yet related disorders; others believe them to be different stages of the same disorder or disease spectrum. Wernicke syndrome is considered the acute phase with a shorter duration and more serious symptoms. Korsakoff syndrome is considered the chronic phase and is a long-lasting condition. (For more information on this disorder, choose “Wernicke” as your search term in the Rare Disease Database.)Batten disease, a rare genetic disorder, belongs to a group of progressive degenerative neurometabolic disorders known as the neuronal ceroid lipofuscinoses. These disorders share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Batten disease is considered the juvenile form of the neuronal ceroid lipofuscinoses (NCLs). The NCLs are characterized by abnormal accumulation of certain fatty, granular substances (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) within nerve cells (neurons) of the brain as well as other tissues of the body that may result in progressive deterioration (atrophy) of certain areas of the brain, neurological impairment, and other characteristic symptoms and physical findings. The symptoms of Batten disease usually become apparent between 5 and 15 years of age when progressive loss of vision, seizures, and progressive neurological degeneration develop. In some cases, initial symptoms may be more vague and include clumsiness, balance problems and behavioral or personality changes. Batten disease is inherited as an autosomal recessive trait and occurs most in families of Northern European or Scandinavian ancestry. (For more information on this disorder, choose “Batten” as your search term in the Rare Disease Database.)Tay-Sachs disease is a rare, neurodegenerative disorder in which deficiency of an enzyme (hexosaminidase A) results in excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells. This abnormal accumulation of gangliosides leads to progressive dysfunction of the central nervous system. This disorder is categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or “digest” nutrients, including certain complex carbohydrates and fats. Symptoms associated with Tay-Sachs disease may include an exaggerated startle response to sudden noises, listlessness, loss of previously acquired skills (i.e., psychomotor regression), and severely diminished muscle tone (hypotonia). With disease progression, affected infants and children may develop cherry-red spots within the middle layer of the eyes, gradual loss of vision, and deafness, increasing muscle stiffness and restricted movements (spasticity), eventual paralysis, uncontrolled electrical disturbances in the brain (seizures), and deterioration of cognitive processes (dementia). The classical form of Tay-Sachs disease occurs during infancy; an adult form (late-onset Tay-Sachs disease) may occur anytime from adolescence to the mid-30s. Tay-Sachs disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Tay-Sachs” as your search term in the Rare Disease Database.)Neuropathy, ataxia and retinitis pigmentosa (NARP) syndrome is a rare genetic disorder. It is characterized by nerve disease affecting the nerves outside of the central nervous system (peripheral neuropathy), an impaired ability to coordinate voluntary movements (ataxia), an eye condition known as retinitis pigmentosa (RP), and a variety of additional abnormalities. RP is a general term for a group of vision disorders that cause progressive degeneration of the membrane lining the eyes (retina) resulting in visual impairment. The specific symptoms of NARP syndrome in each individual vary greatly from case to case. The disorder is a maternally inherited mitochondrial disease. NARP syndrome is caused by a specific mutation affecting the mitochondrial gene known as the ATPase 6 gene. This mutation can also cause a specific subtype of Leigh syndrome known as maternally inherited Leigh syndrome (MILS). In fact, when individuals have more than 90 percent of mutated mitochondrial DNA (mtDNA) in their cells, they are classified as having MILS and not NARP syndrome. Most individuals with NARP syndrome have 70-80 percent of mutated mtDNA. (For more information on this disorder, choose “NARP” as your search term in the Rare Disease Database.)
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Related disorders of Leigh Syndrome. Symptoms of the following disorders can be similar to those of Leigh syndrome. Comparisons may be useful for a differential diagnosis:Wernicke syndrome and Korsakoff syndrome are related disorders that often occur due to a deficiency of thiamine (vitamin B1). Wernicke’s syndrome, also known as Wernicke encephalopathy, is a neurological disease characterized by the clinical triad of confusion, the inability to coordinate voluntary movement (ataxia), and eye (ocular) abnormalities. Korsakoff’s syndrome is a neurological disorder characterized by disproportionate memory loss in relation to other mental aspects. When these two disorders occur together, the term Wernicke-Korsakoff syndrome is used. In the United States, most cases occur in alcoholics. Some researchers believe Wernicke and Korsakoff syndromes are separate yet related disorders; others believe them to be different stages of the same disorder or disease spectrum. Wernicke syndrome is considered the acute phase with a shorter duration and more serious symptoms. Korsakoff syndrome is considered the chronic phase and is a long-lasting condition. (For more information on this disorder, choose “Wernicke” as your search term in the Rare Disease Database.)Batten disease, a rare genetic disorder, belongs to a group of progressive degenerative neurometabolic disorders known as the neuronal ceroid lipofuscinoses. These disorders share certain similar symptoms and are distinguished in part by the age at which such symptoms appear. Batten disease is considered the juvenile form of the neuronal ceroid lipofuscinoses (NCLs). The NCLs are characterized by abnormal accumulation of certain fatty, granular substances (i.e., pigmented lipids [lipopigments] ceroid and lipofuscin) within nerve cells (neurons) of the brain as well as other tissues of the body that may result in progressive deterioration (atrophy) of certain areas of the brain, neurological impairment, and other characteristic symptoms and physical findings. The symptoms of Batten disease usually become apparent between 5 and 15 years of age when progressive loss of vision, seizures, and progressive neurological degeneration develop. In some cases, initial symptoms may be more vague and include clumsiness, balance problems and behavioral or personality changes. Batten disease is inherited as an autosomal recessive trait and occurs most in families of Northern European or Scandinavian ancestry. (For more information on this disorder, choose “Batten” as your search term in the Rare Disease Database.)Tay-Sachs disease is a rare, neurodegenerative disorder in which deficiency of an enzyme (hexosaminidase A) results in excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells. This abnormal accumulation of gangliosides leads to progressive dysfunction of the central nervous system. This disorder is categorized as a lysosomal storage disease. Lysosomes are the major digestive units in cells. Enzymes within lysosomes break down or “digest” nutrients, including certain complex carbohydrates and fats. Symptoms associated with Tay-Sachs disease may include an exaggerated startle response to sudden noises, listlessness, loss of previously acquired skills (i.e., psychomotor regression), and severely diminished muscle tone (hypotonia). With disease progression, affected infants and children may develop cherry-red spots within the middle layer of the eyes, gradual loss of vision, and deafness, increasing muscle stiffness and restricted movements (spasticity), eventual paralysis, uncontrolled electrical disturbances in the brain (seizures), and deterioration of cognitive processes (dementia). The classical form of Tay-Sachs disease occurs during infancy; an adult form (late-onset Tay-Sachs disease) may occur anytime from adolescence to the mid-30s. Tay-Sachs disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Tay-Sachs” as your search term in the Rare Disease Database.)Neuropathy, ataxia and retinitis pigmentosa (NARP) syndrome is a rare genetic disorder. It is characterized by nerve disease affecting the nerves outside of the central nervous system (peripheral neuropathy), an impaired ability to coordinate voluntary movements (ataxia), an eye condition known as retinitis pigmentosa (RP), and a variety of additional abnormalities. RP is a general term for a group of vision disorders that cause progressive degeneration of the membrane lining the eyes (retina) resulting in visual impairment. The specific symptoms of NARP syndrome in each individual vary greatly from case to case. The disorder is a maternally inherited mitochondrial disease. NARP syndrome is caused by a specific mutation affecting the mitochondrial gene known as the ATPase 6 gene. This mutation can also cause a specific subtype of Leigh syndrome known as maternally inherited Leigh syndrome (MILS). In fact, when individuals have more than 90 percent of mutated mitochondrial DNA (mtDNA) in their cells, they are classified as having MILS and not NARP syndrome. Most individuals with NARP syndrome have 70-80 percent of mutated mtDNA. (For more information on this disorder, choose “NARP” as your search term in the Rare Disease Database.)
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Leigh Syndrome
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Diagnosis of Leigh Syndrome
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The diagnosis of Leigh syndrome may be confirmed by a thorough clinical evaluation and a variety of specialized tests, particularly advanced imaging techniques. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain may reveal abnormal areas in certain parts of the brain (i.e., basal ganglia, brain stem, and gray matter). An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures.Small or large cysts may be present in the cerebral cortex of the brain. Laboratory tests may reveal high levels of acidic waste products in the blood (lactic acidosis) as well as elevated levels of pyruvate and alanine. Blood sugar (glucose) may be slightly lower than normal. The enzyme pyruvate carboxylase may be absent from the liver and an inhibitor of thiamine triphosphate (TTP) production may be present in the blood and urine of affected individuals. Some children with Leigh syndrome may have detectable deficiencies of the enzymes pyruvate dehydrogenase complex or cytochrome C oxidase.
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Diagnosis of Leigh Syndrome. The diagnosis of Leigh syndrome may be confirmed by a thorough clinical evaluation and a variety of specialized tests, particularly advanced imaging techniques. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain may reveal abnormal areas in certain parts of the brain (i.e., basal ganglia, brain stem, and gray matter). An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures.Small or large cysts may be present in the cerebral cortex of the brain. Laboratory tests may reveal high levels of acidic waste products in the blood (lactic acidosis) as well as elevated levels of pyruvate and alanine. Blood sugar (glucose) may be slightly lower than normal. The enzyme pyruvate carboxylase may be absent from the liver and an inhibitor of thiamine triphosphate (TTP) production may be present in the blood and urine of affected individuals. Some children with Leigh syndrome may have detectable deficiencies of the enzymes pyruvate dehydrogenase complex or cytochrome C oxidase.
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Leigh Syndrome
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Therapies of Leigh Syndrome
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TreatmentThere are no proven therapies for Leigh Syndrome of any type. Treatment recommendations are based primarily on open label studies, case reports, and personal observations. The treatment of Leigh 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, cardiologists, neurologists, specialists who assess and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an effective child’s treatment.The most common treatment for Leigh syndrome is the administration of thiamine (Vitamin B1) or thiamine derivatives. Some people with this disorder may experience a temporary symptomatic improvement and a slight slowing of the progression of the disease. In those patients with Leigh syndrome who also have a deficiency of pyruvate dehydrogenase enzyme complex, a high fat, low carbohydrate diet may be recommended.Services that benefit people who are visually impaired may also be helpful for some people with Leigh syndrome. Genetic counseling is recommended for families of affected individuals with this disorder. Other treatment is symptomatic and supportive.
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Therapies of Leigh Syndrome. TreatmentThere are no proven therapies for Leigh Syndrome of any type. Treatment recommendations are based primarily on open label studies, case reports, and personal observations. The treatment of Leigh 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, cardiologists, neurologists, specialists who assess and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an effective child’s treatment.The most common treatment for Leigh syndrome is the administration of thiamine (Vitamin B1) or thiamine derivatives. Some people with this disorder may experience a temporary symptomatic improvement and a slight slowing of the progression of the disease. In those patients with Leigh syndrome who also have a deficiency of pyruvate dehydrogenase enzyme complex, a high fat, low carbohydrate diet may be recommended.Services that benefit people who are visually impaired may also be helpful for some people with Leigh syndrome. Genetic counseling is recommended for families of affected individuals with this disorder. Other treatment is symptomatic and supportive.
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Leigh Syndrome
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Overview of Leiomyosarcoma
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Leiomyosarcoma is a malignant (cancerous) tumor that arises from smooth muscle cells. There are essentially two types of muscles in the body – voluntary and involuntary. Smooth muscles are involuntary muscles – the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, smooth muscle that lines the walls of the digestive tract causes wave-like contractions (peristalsis) that aid in the digestion and transport of food. Smooth muscles in the salivary glands cause the glands to squirt saliva into the mouth in response to taking a bite of food. Smooth muscle in the skin causes goose bumps to form in response to cold.Leiomyosarcoma is a form of cancer. The term “cancer” refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant body sites via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including leiomyosarcomas, may be classified based upon the cell type involved, the specific nature of the malignancy, and the disease's clinical course. Leiomyosa usually spreads via the bloodstream. It is very rare to see it in lymphatics.Since smooth muscle is found all over the body, a leiomyosarcoma can form almost anywhere where there are blood vessels, heart, liver, pancreas, genitourinary and gastrointestinal tract, the space behind the abdominal cavity (retroperitoneum), uterus, skin. The uterus is the most common location for a leiomyosarcoma. Most leiomyosarcomas of the gastrointestinal tract are now reclassified as gastrointestinal stromal tumors (GIST – see below)Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant tumors that arise from the connective tissue, which connects, supports and surrounds various structures and organs in the body. Soft tissue includes fat, muscle, nerves, tendons, and blood and lymph vessels. The exact cause of leiomyosarcoma, including uterine leiomyosarcoma, is unknown.
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Overview of Leiomyosarcoma. Leiomyosarcoma is a malignant (cancerous) tumor that arises from smooth muscle cells. There are essentially two types of muscles in the body – voluntary and involuntary. Smooth muscles are involuntary muscles – the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, smooth muscle that lines the walls of the digestive tract causes wave-like contractions (peristalsis) that aid in the digestion and transport of food. Smooth muscles in the salivary glands cause the glands to squirt saliva into the mouth in response to taking a bite of food. Smooth muscle in the skin causes goose bumps to form in response to cold.Leiomyosarcoma is a form of cancer. The term “cancer” refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant body sites via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including leiomyosarcomas, may be classified based upon the cell type involved, the specific nature of the malignancy, and the disease's clinical course. Leiomyosa usually spreads via the bloodstream. It is very rare to see it in lymphatics.Since smooth muscle is found all over the body, a leiomyosarcoma can form almost anywhere where there are blood vessels, heart, liver, pancreas, genitourinary and gastrointestinal tract, the space behind the abdominal cavity (retroperitoneum), uterus, skin. The uterus is the most common location for a leiomyosarcoma. Most leiomyosarcomas of the gastrointestinal tract are now reclassified as gastrointestinal stromal tumors (GIST – see below)Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant tumors that arise from the connective tissue, which connects, supports and surrounds various structures and organs in the body. Soft tissue includes fat, muscle, nerves, tendons, and blood and lymph vessels. The exact cause of leiomyosarcoma, including uterine leiomyosarcoma, is unknown.
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Leiomyosarcoma
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Symptoms of Leiomyosarcoma
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The symptoms of a leiomyosarcoma vary depending upon the exact location, size, and spread of the tumor. A leiomyosarcoma, especially in the early stages, may not be associated with any obvious symptoms (asymptomatic). General symptoms associated with cancer may occur including fatigue, fever, weight loss, a general feeling of ill health (malaise), and nausea and vomiting.Pain may occur in the affected area but is uncommon. Swelling usually occurs and a mass is commonly detected. Additional symptoms are specific to the exact location of the tumor. The tumors may cause bleeding in the gastrointestinal tract and cause black, tarry, foul-smelling stools (melena), or vomiting of blood (hematemesis) or abdominal discomforts). A leiomyosarcoma of the uterus may cause abnormal bleeding from the uterus into and the vagina, with abnormal vaginal discharge, and a change in bladder or bowel habits.Most forms of leiomyosarcoma are aggressive tumors that may spread (metastasize) to other areas of the body such as the lungs or liver, potentially causing life-threatening complications. Leiomyosarcoma has a high risk of recurring after treatment, if not diagnosed early.
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Symptoms of Leiomyosarcoma. The symptoms of a leiomyosarcoma vary depending upon the exact location, size, and spread of the tumor. A leiomyosarcoma, especially in the early stages, may not be associated with any obvious symptoms (asymptomatic). General symptoms associated with cancer may occur including fatigue, fever, weight loss, a general feeling of ill health (malaise), and nausea and vomiting.Pain may occur in the affected area but is uncommon. Swelling usually occurs and a mass is commonly detected. Additional symptoms are specific to the exact location of the tumor. The tumors may cause bleeding in the gastrointestinal tract and cause black, tarry, foul-smelling stools (melena), or vomiting of blood (hematemesis) or abdominal discomforts). A leiomyosarcoma of the uterus may cause abnormal bleeding from the uterus into and the vagina, with abnormal vaginal discharge, and a change in bladder or bowel habits.Most forms of leiomyosarcoma are aggressive tumors that may spread (metastasize) to other areas of the body such as the lungs or liver, potentially causing life-threatening complications. Leiomyosarcoma has a high risk of recurring after treatment, if not diagnosed early.
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Leiomyosarcoma
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Causes of Leiomyosarcoma
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The exact cause of leiomyosarcoma is unknown. Researchers speculate that genetic factors may play a contributing role in causing LMS.In individuals with cancer, including leiomyosarcoma, malignancies may develop due to abnormal changes in the structure and orientation of certain cells known as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.
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Causes of Leiomyosarcoma. The exact cause of leiomyosarcoma is unknown. Researchers speculate that genetic factors may play a contributing role in causing LMS.In individuals with cancer, including leiomyosarcoma, malignancies may develop due to abnormal changes in the structure and orientation of certain cells known as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.
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Leiomyosarcoma
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Affects of Leiomyosarcoma
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Leiomyosarcomas affect both males and females. Leiomyosarcoma is a form of soft tissue sarcoma. According to the American Cancer Society, at least 15,000 new cases of soft tissue sarcoma occur each year in the U.S. Soft tissue sarcomas affect men and women equally and occur more often in adults than children or adolescents. Soft tissue sarcomas account for 1 percent of all adult cancers in the U.S. According to one estimate, leiomyosarcomas account for 7-11 percent of all cases of soft tissue sarcomas.
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Affects of Leiomyosarcoma. Leiomyosarcomas affect both males and females. Leiomyosarcoma is a form of soft tissue sarcoma. According to the American Cancer Society, at least 15,000 new cases of soft tissue sarcoma occur each year in the U.S. Soft tissue sarcomas affect men and women equally and occur more often in adults than children or adolescents. Soft tissue sarcomas account for 1 percent of all adult cancers in the U.S. According to one estimate, leiomyosarcomas account for 7-11 percent of all cases of soft tissue sarcomas.
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Leiomyosarcoma
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Related disorders of Leiomyosarcoma
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Symptoms of the following disorders can be similar to those of a leiomyosarcoma. Comparisons may be useful for a differential diagnosis.Leiomyomas are benign tumors arising from the smooth muscle. The uterus and the gastrointestinal tract are the most common locations for this tumor. In some cases, multiple leiomyomas form. Leiomyomas often do not cause symptoms (asymptomatic). In some cases they may be associated with pain or swelling in the affected area. Leiomyomas may grow large enough to compress nearby structures causing a variety of symptoms and necessitating surgical removal. In extremely rare cases, leiomyomas may progress to become cancerous (malignant transformation). The exact cause of leiomyomas is unknown. (For more information on this condition, choose “leiomyoma” as your search term in the Rare Disease Database.)Gastrointestinal stromal tumors (GIST) belong to a group of cancers known as soft tissue sarcomas. Tumors usually arise from the intestinal tract with the most common site being the stomach, followed by the small intestine, and the colon/rectum with rare cases arising in the esophagus. There are also tumors that appear to arise in the membranous tissue lining the wall of the stomach (peritoneum) or in a fold of such membranous tissue (the omentum). There are also case reports of tumors arising in the appendix and/or pancreas. These tumors most commonly present with abdominal pain, bleeding or signs of intestinal obstruction. They spread most commonly to sites within the abdominal cavity and to the liver, although there are rare cases of spread to the lungs and bone. GIST results from a change in one of two genes, KIT or PDGFR, which leads to continued growth and division of tumor cells. There are a few reported cases of families in which a gene mutation is inherited; however, the majority of tumors are sporadic and not inherited. Treatment is with surgery. In individuals in whom the disease has spread, treatment may include surgery when possible and the administration of imatinib mesylate (Gleevec, Glivec), a tyrosine kinase inhibitor that inhibits the KIT or PDGFR responsible for tumor growth. Imatinib mesylate can delay or prevent recurrence of GIST when given after the tumor has been removed (resection). The role of imatinib mesylate in pediatric GIST is being studied at this time. (For more information on this disorder, choose “GIST” as your search term in the Rare Disease Database.)
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Related disorders of Leiomyosarcoma. Symptoms of the following disorders can be similar to those of a leiomyosarcoma. Comparisons may be useful for a differential diagnosis.Leiomyomas are benign tumors arising from the smooth muscle. The uterus and the gastrointestinal tract are the most common locations for this tumor. In some cases, multiple leiomyomas form. Leiomyomas often do not cause symptoms (asymptomatic). In some cases they may be associated with pain or swelling in the affected area. Leiomyomas may grow large enough to compress nearby structures causing a variety of symptoms and necessitating surgical removal. In extremely rare cases, leiomyomas may progress to become cancerous (malignant transformation). The exact cause of leiomyomas is unknown. (For more information on this condition, choose “leiomyoma” as your search term in the Rare Disease Database.)Gastrointestinal stromal tumors (GIST) belong to a group of cancers known as soft tissue sarcomas. Tumors usually arise from the intestinal tract with the most common site being the stomach, followed by the small intestine, and the colon/rectum with rare cases arising in the esophagus. There are also tumors that appear to arise in the membranous tissue lining the wall of the stomach (peritoneum) or in a fold of such membranous tissue (the omentum). There are also case reports of tumors arising in the appendix and/or pancreas. These tumors most commonly present with abdominal pain, bleeding or signs of intestinal obstruction. They spread most commonly to sites within the abdominal cavity and to the liver, although there are rare cases of spread to the lungs and bone. GIST results from a change in one of two genes, KIT or PDGFR, which leads to continued growth and division of tumor cells. There are a few reported cases of families in which a gene mutation is inherited; however, the majority of tumors are sporadic and not inherited. Treatment is with surgery. In individuals in whom the disease has spread, treatment may include surgery when possible and the administration of imatinib mesylate (Gleevec, Glivec), a tyrosine kinase inhibitor that inhibits the KIT or PDGFR responsible for tumor growth. Imatinib mesylate can delay or prevent recurrence of GIST when given after the tumor has been removed (resection). The role of imatinib mesylate in pediatric GIST is being studied at this time. (For more information on this disorder, choose “GIST” as your search term in the Rare Disease Database.)
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Leiomyosarcoma
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Diagnosis of Leiomyosarcoma
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A diagnosis of a leiomyosarcoma may be made based upon a detailed patient history, a thorough clinical evaluation and a variety of tests including blood tests, surgical removal and microscopic examination of tissue (biopsies) and various imaging techniques. In some cases, individuals may notice a painful lump or mass in the affected area. A key diagnostic aspect is distinguishing malignant leiomyosarcoma from its benign counterpart, the leiomyoma.To confirm a diagnosis of leiomyosarcoma a fine-needle aspiration may be performed. Fine-need aspiration (FNA) is a diagnostic technique in which a thin, hollow needle is passed though the skin and inserted into the nodule or mass to withdraw small samples of tissue. The collected tissue is then studied under a microscope. In some cases, FNA may prove inconclusive and physicians may perform a core (Trucut) biopsy or an incisional biopsy. During Trucut or incisional biopsy, a small sample tissue is surgically removed and sent to a pathology laboratory where it is processed and studied to determine its microscopic structure and makeup (histopathology).Specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with leiomyosarcomas. Such imaging techniques may include computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and ultrasound. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During an ultrasound reflected sound waves create an image of internal organs and other structures within the body.Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
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Diagnosis of Leiomyosarcoma. A diagnosis of a leiomyosarcoma may be made based upon a detailed patient history, a thorough clinical evaluation and a variety of tests including blood tests, surgical removal and microscopic examination of tissue (biopsies) and various imaging techniques. In some cases, individuals may notice a painful lump or mass in the affected area. A key diagnostic aspect is distinguishing malignant leiomyosarcoma from its benign counterpart, the leiomyoma.To confirm a diagnosis of leiomyosarcoma a fine-needle aspiration may be performed. Fine-need aspiration (FNA) is a diagnostic technique in which a thin, hollow needle is passed though the skin and inserted into the nodule or mass to withdraw small samples of tissue. The collected tissue is then studied under a microscope. In some cases, FNA may prove inconclusive and physicians may perform a core (Trucut) biopsy or an incisional biopsy. During Trucut or incisional biopsy, a small sample tissue is surgically removed and sent to a pathology laboratory where it is processed and studied to determine its microscopic structure and makeup (histopathology).Specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with leiomyosarcomas. Such imaging techniques may include computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and ultrasound. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During an ultrasound reflected sound waves create an image of internal organs and other structures within the body.Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
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Leiomyosarcoma
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Therapies of Leiomyosarcoma
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TreatmentThe therapeutic management of individuals with a leiomyosarcoma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), surgeons (surgical oncologist), oncology nurses, and other specialists.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to distant sites; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.The main form of treatment for leiomyosarcomas is surgical excision and removal of the entire tumor and surrounding tissue (resection). Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques. Surgical options are dictated by the size, location and spread of a tumor.In addition, based upon primary tumor site, size, and other factors, recommended standard therapy may often include postoperative radiation to help treat known or possible residual disease. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying.In most cases, however, chemotherapy and radiation therapy have had only limited success in slowing or stopping progression of leiomyosarcomas. Because of the rarity of leiomyosarcomas no standard or overall effective type of chemotherapy or radiation therapy has been identified. The use of chemotherapy and radiation therapy for the treatment of leiomyosarcomas remains under investigation. (Please see the “Investigational Therapies” section below.)In 2015, Yondelis was approved as a chemotherapy for liposarcoma and leiomyosarcoma that cannot be removed by surgery or patients that previously underwent treatment that contained anthracycline. Yondelis is marketed by Janssen Products.
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Therapies of Leiomyosarcoma. TreatmentThe therapeutic management of individuals with a leiomyosarcoma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), surgeons (surgical oncologist), oncology nurses, and other specialists.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to distant sites; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.The main form of treatment for leiomyosarcomas is surgical excision and removal of the entire tumor and surrounding tissue (resection). Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques. Surgical options are dictated by the size, location and spread of a tumor.In addition, based upon primary tumor site, size, and other factors, recommended standard therapy may often include postoperative radiation to help treat known or possible residual disease. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying.In most cases, however, chemotherapy and radiation therapy have had only limited success in slowing or stopping progression of leiomyosarcomas. Because of the rarity of leiomyosarcomas no standard or overall effective type of chemotherapy or radiation therapy has been identified. The use of chemotherapy and radiation therapy for the treatment of leiomyosarcomas remains under investigation. (Please see the “Investigational Therapies” section below.)In 2015, Yondelis was approved as a chemotherapy for liposarcoma and leiomyosarcoma that cannot be removed by surgery or patients that previously underwent treatment that contained anthracycline. Yondelis is marketed by Janssen Products.
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Leiomyosarcoma
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Overview of Leiomyosarcoma, Inferior Vena Cava
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Leiomyosarcoma of the inferior vena cava is an extremely rare malignant (cancerous) tumor arising from the smooth muscle lining the walls of the large vein that carries blood from the lower body to the heart (inferior vena cava). There are essentially two types of muscles in the body – voluntary and involuntary. Smooth muscles are involuntary muscles – the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, the smooth muscle in walls of blood vessels contracts to help regulate blood flow.Leiomyosarcomas are a form of cancer. The term “cancer” refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including leiomyosarcomas, are graded according to certain histological parameters evaluated microscopically and this grade (low, intermediate, or high) gives the clinician an indication of the potential clinical aggressiveness of the tumor.Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant tumors that arise from the connective tissue, which connects, supports and surrounds various structures and organs in the body. Soft tissue includes fat, muscle, nerve, tendons, tissue surrounding the joints (synovial tissue), and blood and lymph vessels. The exact cause of sarcomas including leiomyosarcomas is unknown.
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Overview of Leiomyosarcoma, Inferior Vena Cava. Leiomyosarcoma of the inferior vena cava is an extremely rare malignant (cancerous) tumor arising from the smooth muscle lining the walls of the large vein that carries blood from the lower body to the heart (inferior vena cava). There are essentially two types of muscles in the body – voluntary and involuntary. Smooth muscles are involuntary muscles – the brain has no conscious control over them. Smooth muscles react involuntarily in response to various stimuli. For example, the smooth muscle in walls of blood vessels contracts to help regulate blood flow.Leiomyosarcomas are a form of cancer. The term “cancer” refers to a group of diseases characterized by abnormal, uncontrolled cellular growth that invades surrounding tissues and may spread (metastasize) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. Different forms of cancer, including leiomyosarcomas, are graded according to certain histological parameters evaluated microscopically and this grade (low, intermediate, or high) gives the clinician an indication of the potential clinical aggressiveness of the tumor.Leiomyosarcoma is classified as a soft tissue sarcoma. Sarcomas are malignant tumors that arise from the connective tissue, which connects, supports and surrounds various structures and organs in the body. Soft tissue includes fat, muscle, nerve, tendons, tissue surrounding the joints (synovial tissue), and blood and lymph vessels. The exact cause of sarcomas including leiomyosarcomas is unknown.
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Leiomyosarcoma, Inferior Vena Cava
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Symptoms of Leiomyosarcoma, Inferior Vena Cava
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The symptoms associated with a leiomyosarcoma of the IVC vary greatly from case to case. The exact location and size of the tumor within the vena cava determines the specific symptoms that occur and whether or not the tumor can be removed surgically. The inferior vena cava runs from the pelvis to the thoracic cavity, emptying into the heart. The inferior vena cava is connected to numerous veins including the main vein of the liver (hepatic vein) and the main vein of the kidneys (renal vein). Most tumors occur in the middle portion of the IVC (i.e., between the hepatic and renal veins or the lower portion of the IVC (i.e., below the renal vein). Less often, a leiomyosarcoma develops within the upper portion of the IVC (i.e., above the hepatic vein). Many individuals with a leiomyosarcoma of the inferior vena cava do not exhibit any symptoms (asymptomatic). The tumor may grow and spread without any apparent signs. Eventually, some individuals may develop a palpable mass in the stomach. Vague, general symptoms may occur including abdominal pain, fever, weakness, weight loss, vomiting, difficulty breathing (dyspnea), and night sweats. A leiomyosarcoma's location within the IVC may be associated with additional symptoms specific to that area. Tumors in the lower portion of the inferior vena cava may be associated with lower back pain and generalized swelling due to the abnormal accumulation of fluid (edema), especially in the legs and around the eyes. A leiomyosarcoma of the middle portion may cause narrowing or blockage (occlusion) of the renal vein resulting in nephrotic syndrome – a kidney condition characterized by protein in the urine, low blood protein levels, and edema affecting the limbs and the area around the eyes. A leiomyosarcoma of the upper segment may cause the development of Budd-Chiari syndrome and, in extremely rare cases, irregular heartbeat rhythms (arrhythmia). (For more information on this disorder, see the Related Disorders section of this report.)Another complication associated with a leiomyosarcoma of the IVC is deep vein thrombosis (DVT), a condition characterized by blood clots (thrombosis) in the deep veins of the lower legs or thigh that often hamper circulation. A piece of the blood clot can potentially break off and travel to another area of the body (embolize) where it lodges in a vein or artery cutting off blood flow to a vital organ such as the brain or lungs.
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Symptoms of Leiomyosarcoma, Inferior Vena Cava. The symptoms associated with a leiomyosarcoma of the IVC vary greatly from case to case. The exact location and size of the tumor within the vena cava determines the specific symptoms that occur and whether or not the tumor can be removed surgically. The inferior vena cava runs from the pelvis to the thoracic cavity, emptying into the heart. The inferior vena cava is connected to numerous veins including the main vein of the liver (hepatic vein) and the main vein of the kidneys (renal vein). Most tumors occur in the middle portion of the IVC (i.e., between the hepatic and renal veins or the lower portion of the IVC (i.e., below the renal vein). Less often, a leiomyosarcoma develops within the upper portion of the IVC (i.e., above the hepatic vein). Many individuals with a leiomyosarcoma of the inferior vena cava do not exhibit any symptoms (asymptomatic). The tumor may grow and spread without any apparent signs. Eventually, some individuals may develop a palpable mass in the stomach. Vague, general symptoms may occur including abdominal pain, fever, weakness, weight loss, vomiting, difficulty breathing (dyspnea), and night sweats. A leiomyosarcoma's location within the IVC may be associated with additional symptoms specific to that area. Tumors in the lower portion of the inferior vena cava may be associated with lower back pain and generalized swelling due to the abnormal accumulation of fluid (edema), especially in the legs and around the eyes. A leiomyosarcoma of the middle portion may cause narrowing or blockage (occlusion) of the renal vein resulting in nephrotic syndrome – a kidney condition characterized by protein in the urine, low blood protein levels, and edema affecting the limbs and the area around the eyes. A leiomyosarcoma of the upper segment may cause the development of Budd-Chiari syndrome and, in extremely rare cases, irregular heartbeat rhythms (arrhythmia). (For more information on this disorder, see the Related Disorders section of this report.)Another complication associated with a leiomyosarcoma of the IVC is deep vein thrombosis (DVT), a condition characterized by blood clots (thrombosis) in the deep veins of the lower legs or thigh that often hamper circulation. A piece of the blood clot can potentially break off and travel to another area of the body (embolize) where it lodges in a vein or artery cutting off blood flow to a vital organ such as the brain or lungs.
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Causes of Leiomyosarcoma, Inferior Vena Cava
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The exact cause of leiomyosarcomas of the IVC is unknown. They often occur spontaneously, for no apparent reason. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer. Malignancies, including leiomyosarcoma, develop due to abnormal changes in the structure and orientation of certain cells known as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.Leiomyosarcomas are associated with specific genetic and environmental risk factors. Certain inherited conditions that run in families may increase the risk of developing a leiomyosarcoma. These disorders include Gardner syndrome, Li-Fraumeni syndrome, Werner syndrome, neurofibromatosis and several immune deficiency syndromes. The exact association between leiomyosarcomas and these disorders is not understood. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Individuals exposed to high dose radiation may have a higher than normal risk of developing leiomyosarcomas. Researchers have speculated that exposure to certain chemicals (e.g., herbicides) may also be linked to an increased risk of developing leiomyosarcomas.
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Causes of Leiomyosarcoma, Inferior Vena Cava. The exact cause of leiomyosarcomas of the IVC is unknown. They often occur spontaneously, for no apparent reason. Researchers speculate that genetic and immunologic abnormalities, environmental factors (e.g., exposure to ultraviolet rays, certain chemicals, ionizing radiation), diet, stress, and/or other factors may play contributing roles in causing specific types of cancer. Investigators are conducting ongoing basic research to learn more about the many factors that may result in cancer. Malignancies, including leiomyosarcoma, develop due to abnormal changes in the structure and orientation of certain cells known as oncogenes or tumor suppressor genes. Oncogenes control cell growth; tumor suppressor genes control cell division and ensure that cells die at the proper time. The specific cause of changes to these genes is unknown. However, current research suggests that abnormalities of DNA (deoxyribonucleic acid), which is the carrier of the body's genetic code, are the underlying basis of cellular malignant transformation. These abnormal genetic changes may occur spontaneously for unknown reasons or, more rarely, may be inherited.Leiomyosarcomas are associated with specific genetic and environmental risk factors. Certain inherited conditions that run in families may increase the risk of developing a leiomyosarcoma. These disorders include Gardner syndrome, Li-Fraumeni syndrome, Werner syndrome, neurofibromatosis and several immune deficiency syndromes. The exact association between leiomyosarcomas and these disorders is not understood. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)Individuals exposed to high dose radiation may have a higher than normal risk of developing leiomyosarcomas. Researchers have speculated that exposure to certain chemicals (e.g., herbicides) may also be linked to an increased risk of developing leiomyosarcomas.
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Affects of Leiomyosarcoma, Inferior Vena Cava
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Leiomyosarcomas of the IVC affect females more often than males. Most cases are diagnosed in adult women in the fifth or sixth decade of life. Leiomyosarcoma of the IVC was first identified by a German doctor in 1871. However, as of 2006, fewer than 300 cases had been reported in the medical literature. Although extremely rare, it is the most common primary malignancy of the inferior vena cava.Leiomyosarcoma is a form of soft tissue sarcoma. According to the American Cancer Society, 9,530 new cases of soft tissue sarcoma will occur in the United States in 2006. Soft tissue sarcomas affect men slightly more often than women and occur more often in adults than children and adolescents.
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Affects of Leiomyosarcoma, Inferior Vena Cava. Leiomyosarcomas of the IVC affect females more often than males. Most cases are diagnosed in adult women in the fifth or sixth decade of life. Leiomyosarcoma of the IVC was first identified by a German doctor in 1871. However, as of 2006, fewer than 300 cases had been reported in the medical literature. Although extremely rare, it is the most common primary malignancy of the inferior vena cava.Leiomyosarcoma is a form of soft tissue sarcoma. According to the American Cancer Society, 9,530 new cases of soft tissue sarcoma will occur in the United States in 2006. Soft tissue sarcomas affect men slightly more often than women and occur more often in adults than children and adolescents.
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Related disorders of Leiomyosarcoma, Inferior Vena Cava
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Symptoms of the following disorders can be similar to those of leiomyosarcomas of the IVC. Comparisons may be useful for a differential diagnosis.Angiosarcoma is a rare malignant (cancerous) tumor that arises from the cells that line blood or lymph vessels. These tumors are often aggressive and spread (metastasize) to other areas of the body. In most cases there are no apparent symptoms in the early stages (asymptomatic). Eventually, a palpable mass or growth may be detectable. Since angiosarcomas are prone to bleeding (hemorrhagic), the palpable mass they produce usually has a dark, purple appearance of the skin surface. Pain may occur in some cases due to compression of nearby nerves. The exact cause of an angiosarcoma is unknown. Renal cell carcinoma is a form of kidney cancer. Some individuals with renal cell carcinoma do not have symptoms (asymptomatic). When symptoms are present, they may include blood in the urine; urine that is brown or rusty-colored; abdominal pain; enlargement of one testicle or varicose veins of the testis (varicocele) in a male patient; fever; a thin, malnourished appearance; vision abnormalities; and elevated blood pressure. The most common feature of the syndrome is the passing of blood in the urine (hematuria). Renal cell carcinoma can spread to affect the inferior vena cava. The exact cause of renal cell carcinoma is unknown. (For more information on this disorder, choose “renal cell carcinoma” as your search term in the Rare Disease Database.)The following disorder may be with a sign or symptom of a leiomyosarcoma of the IVC.Budd-Chiari syndrome is a rare disorder characterized by narrowing and obstruction (occlusion) of the veins of the liver (hepatic veins). Symptoms associated with Budd Chiari syndrome include pain in the upper right part of the abdomen, an abnormally large liver (hepatomegaly), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that lines the abdominal cavity (ascites). Additional findings that may be associated with the disorder include nausea, vomiting, and/or an abnormally large spleen (splenomegaly). The severity of the disorder varies from case to case, depending upon the site and number of affected veins. In some cases, if the major hepatic veins are involved, high pressure (portal hypertension) develops in the veins carrying blood from the gastrointestinal tract to the heart via the liver. (For more information on this disorder, choose “Budd Chiari” as your search term in the Rare Disease Database.)
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Related disorders of Leiomyosarcoma, Inferior Vena Cava. Symptoms of the following disorders can be similar to those of leiomyosarcomas of the IVC. Comparisons may be useful for a differential diagnosis.Angiosarcoma is a rare malignant (cancerous) tumor that arises from the cells that line blood or lymph vessels. These tumors are often aggressive and spread (metastasize) to other areas of the body. In most cases there are no apparent symptoms in the early stages (asymptomatic). Eventually, a palpable mass or growth may be detectable. Since angiosarcomas are prone to bleeding (hemorrhagic), the palpable mass they produce usually has a dark, purple appearance of the skin surface. Pain may occur in some cases due to compression of nearby nerves. The exact cause of an angiosarcoma is unknown. Renal cell carcinoma is a form of kidney cancer. Some individuals with renal cell carcinoma do not have symptoms (asymptomatic). When symptoms are present, they may include blood in the urine; urine that is brown or rusty-colored; abdominal pain; enlargement of one testicle or varicose veins of the testis (varicocele) in a male patient; fever; a thin, malnourished appearance; vision abnormalities; and elevated blood pressure. The most common feature of the syndrome is the passing of blood in the urine (hematuria). Renal cell carcinoma can spread to affect the inferior vena cava. The exact cause of renal cell carcinoma is unknown. (For more information on this disorder, choose “renal cell carcinoma” as your search term in the Rare Disease Database.)The following disorder may be with a sign or symptom of a leiomyosarcoma of the IVC.Budd-Chiari syndrome is a rare disorder characterized by narrowing and obstruction (occlusion) of the veins of the liver (hepatic veins). Symptoms associated with Budd Chiari syndrome include pain in the upper right part of the abdomen, an abnormally large liver (hepatomegaly), and/or accumulation of fluid in the space (peritoneal cavity) between the two layers of the membrane that lines the abdominal cavity (ascites). Additional findings that may be associated with the disorder include nausea, vomiting, and/or an abnormally large spleen (splenomegaly). The severity of the disorder varies from case to case, depending upon the site and number of affected veins. In some cases, if the major hepatic veins are involved, high pressure (portal hypertension) develops in the veins carrying blood from the gastrointestinal tract to the heart via the liver. (For more information on this disorder, choose “Budd Chiari” as your search term in the Rare Disease Database.)
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Diagnosis of Leiomyosarcoma, Inferior Vena Cava
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A tumor affecting the inferior vena cava is often found incidentally on routine imaging exams. Various specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with leiomyosarcomas.Such imaging techniques may include computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and ultrasound. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During an ultrasound reflected sound waves create an image of internal organs and other structures within the body.Surgical removal and microscopic evaluation of affected tissue may confirm a diagnosis of a leiomyosarcoma. However, because of the location of the inferior vena cava, it may be difficult to perform a biopsy. In some cases, a CT-guided biopsy may be used to obtain a tissue sample and confirm a diagnosis of leiomyosarcoma.A procedure known as an angiography is sometimes used to aid in the diagnosis of leiomyosarcoma of the IVC. During an angiography, a special fluid known as contrast dye is injected into the body. This fluid is visible upon x-rays and allows for examination of blood vessels. X-rays of blood vessels taken using an angiography are called angiograms.Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
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Diagnosis of Leiomyosarcoma, Inferior Vena Cava. A tumor affecting the inferior vena cava is often found incidentally on routine imaging exams. Various specialized imaging techniques may be used to help evaluate the size, placement, and extension of the tumor and to serve as an aid for future surgical procedures, among individuals with leiomyosarcomas.Such imaging techniques may include computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and ultrasound. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues. During an ultrasound reflected sound waves create an image of internal organs and other structures within the body.Surgical removal and microscopic evaluation of affected tissue may confirm a diagnosis of a leiomyosarcoma. However, because of the location of the inferior vena cava, it may be difficult to perform a biopsy. In some cases, a CT-guided biopsy may be used to obtain a tissue sample and confirm a diagnosis of leiomyosarcoma.A procedure known as an angiography is sometimes used to aid in the diagnosis of leiomyosarcoma of the IVC. During an angiography, a special fluid known as contrast dye is injected into the body. This fluid is visible upon x-rays and allows for examination of blood vessels. X-rays of blood vessels taken using an angiography are called angiograms.Laboratory tests and specialized imaging tests may also be conducted to determine possible infiltration of regional lymph nodes and the presence of distant metastases.
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Therapies of Leiomyosarcoma, Inferior Vena Cava
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TreatmentThe therapeutic management of individuals with a leiomyosarcoma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), oncological surgeons, oncology nurses, and other healthcare specialists.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to lymph nodes or distant sites; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.The main form of treatment for a leiomyosarcoma of the IVC is surgical excision and removal of the entire tumor and surrounding tissue (resection). Surgery is the mainstay of treatment for leiomyosarcoma and should be performed by experienced oncological surgeons (and not general surgeons unfamiliar with the surgical approach). In some cases only a portion of the tumor can be safely removed. Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques.Although radiation therapy provides limited or no benefit in treating most forms of soft tissue sarcoma, some reports suggest that it may be helpful for individuals with leiomyosarcomas of the IVC. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying.In most cases, however, chemotherapy and radiation therapy have had only limited success in slowing or stopping progression of leiomyosarcomas. Because of the rarity of leiomyosarcomas occurring in the IVC no standard or overall effective type of chemotherapy or radiation therapy has been identified. The use of chemotherapy and radiation therapy for the treatment of leiomyosarcomas in general remains under investigation. (Please see the "Investigational Therapies" section below.)
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Therapies of Leiomyosarcoma, Inferior Vena Cava. TreatmentThe therapeutic management of individuals with a leiomyosarcoma may require the coordinated efforts of a team of medical professionals, such as physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), specialists in the use of radiation to treat cancer (radiation oncologists), oncological surgeons, oncology nurses, and other healthcare specialists.Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as primary tumor location, extent of the primary tumor (stage), and degree of malignancy (grade); whether the tumor has spread to lymph nodes or distant sites; an individual's age and general health; and/or other elements. Decisions concerning the use of particular interventions should be made by physicians and other members of the health care team in careful consultation with the patient, based upon the specifics of the case; a thorough discussion of the potential benefits and risks; patient preference; and other appropriate factors.The main form of treatment for a leiomyosarcoma of the IVC is surgical excision and removal of the entire tumor and surrounding tissue (resection). Surgery is the mainstay of treatment for leiomyosarcoma and should be performed by experienced oncological surgeons (and not general surgeons unfamiliar with the surgical approach). In some cases only a portion of the tumor can be safely removed. Depending upon the location of the primary tumor, surgical procedures may also include the use of certain reconstructive techniques.Although radiation therapy provides limited or no benefit in treating most forms of soft tissue sarcoma, some reports suggest that it may be helpful for individuals with leiomyosarcomas of the IVC. If initial surgery is not an option due to the specific location and/or progression of the malignancy, therapy may include radiation alone. Radiation therapy preferentially destroys or injures rapidly dividing cells, primarily cancerous cells. However, some healthy cells (e.g., hair follicles, bone marrow, etc.) may also be damaged, leading to certain side effects. Thus, during such therapy, the radiation is passed through diseased tissue in carefully calculated dosages to destroy cancer cells while minimizing exposure and damage to normal cells. Radiation therapy works to destroy cancer cells by depositing energy that damages their genetic material, preventing or slowing their growth and replication.For some affected individuals, particularly those who have locally advanced, metastatic, or recurrent disease, therapy with certain anticancer drugs (chemotherapy) may also be recommended, possibly in combination with surgical procedures and/or radiation; physicians may recommend combination therapy with multiple chemotherapeutic drugs that have different modes of action in destroying tumor cells and/or preventing them from multiplying.In most cases, however, chemotherapy and radiation therapy have had only limited success in slowing or stopping progression of leiomyosarcomas. Because of the rarity of leiomyosarcomas occurring in the IVC no standard or overall effective type of chemotherapy or radiation therapy has been identified. The use of chemotherapy and radiation therapy for the treatment of leiomyosarcomas in general remains under investigation. (Please see the "Investigational Therapies" section below.)
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Overview of Leishmaniasis
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SummaryLeishmaniasis is an infectious disease caused by protozoan parasites of the genus, Leishmania. Protozoa are microscopic, single-cell organisms. The parasites that cause the disease are transmitted to people through the bites of certain species of infected sand flies. In humans, these parasites cause three main forms of infection: cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. In each of these forms, infection ranges from causing no symptoms (asymptomatic infection) to severe, even life-threatening complications. Only a small percentage of people infected by Leishmania parasites will go on to develop disease. Leishmaniasis is seldom encountered in the United States. Most people from the U.S. who become infected do so because of travel to or living in regions around the world where the disease is common. Military personnel and contractors who serve in those areas are also at risk. In rare instances, there have been reports of cutaneous leishmaniasis acquired in the U.S. in Texas and Oklahoma.IntroductionLeishmaniasis is broadly classified based upon its location in the Western or Eastern hemispheres. In the Western Hemisphere the disease is known as New World leishmaniasis, and is found in some areas of Mexico, Central America and South America. In the Eastern Hemisphere, the disease is known as Old World leishmaniasis, and is found in certain parts of Asia, the Middle East, southern Europe (particularly the Mediterranean area), North Africa and tropical regions of Africa. New World and Old World leishmaniasis are caused by different Leishmania species.
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Overview of Leishmaniasis. SummaryLeishmaniasis is an infectious disease caused by protozoan parasites of the genus, Leishmania. Protozoa are microscopic, single-cell organisms. The parasites that cause the disease are transmitted to people through the bites of certain species of infected sand flies. In humans, these parasites cause three main forms of infection: cutaneous leishmaniasis, mucosal leishmaniasis and visceral leishmaniasis. In each of these forms, infection ranges from causing no symptoms (asymptomatic infection) to severe, even life-threatening complications. Only a small percentage of people infected by Leishmania parasites will go on to develop disease. Leishmaniasis is seldom encountered in the United States. Most people from the U.S. who become infected do so because of travel to or living in regions around the world where the disease is common. Military personnel and contractors who serve in those areas are also at risk. In rare instances, there have been reports of cutaneous leishmaniasis acquired in the U.S. in Texas and Oklahoma.IntroductionLeishmaniasis is broadly classified based upon its location in the Western or Eastern hemispheres. In the Western Hemisphere the disease is known as New World leishmaniasis, and is found in some areas of Mexico, Central America and South America. In the Eastern Hemisphere, the disease is known as Old World leishmaniasis, and is found in certain parts of Asia, the Middle East, southern Europe (particularly the Mediterranean area), North Africa and tropical regions of Africa. New World and Old World leishmaniasis are caused by different Leishmania species.
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Symptoms of Leishmaniasis
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Leishmaniasis can affect people in different ways. Some have truly silent infection, and do not develop any signs or symptoms. Other people develop mild to moderate disease, but some develop severe infection which can lead to permanent damage and potentially life-threatening complications.CUTANEOUS LEISHMANIASIS
This is the most common form of leishmaniasis. Symptoms may begin within weeks to months after being bitten by an infected sand fly. Affected individuals may develop one or more sores (skin lesions), particularly on exposed parts of the body such as the face, ears and the arms and legs. The lesions form at the site where the bite occurs. The lesions may be papules (bumps) or nodules (solid, raised bumps), plaques (spread out, raised lesions) or ulcers (open, eroded areas like craters). Skin lesions may change in size, becoming smaller but often enlarge and do not heal. Sores may be moist and leak fluid (like pus) or may be dry and crust over and are usually painless. Individuals may develop lesions that are limited to one area of the body and may slowly heal on their own over 6-18 months. Lesions, however, usually leave noticeable scars. Sometimes, individuals also have swollen, adjacent lymph nodes (lymphadenopathy).Diffuse Cutaneous Leishmaniasis
This very rare form is characterized by an initial skin lesion that spreads to affect the skin of multiple different areas of the body. Individuals often have a poorly functioning immune system, which leaves them susceptible to widespread involvement of the skin, predisposes to a poor response to treatment and permits infection to last indefinitely. Affected individuals may have multiple plaques, ulcers and nodules all over their body. Diffuse cutaneous leishmaniasis progresses slowly but is a chronic condition that routinely recurs after treatment even if treatment appears to have been initially effective.Leishmaniasis Recidivans
This term is used to define the recurrence of a skin lesion years after the initial lesion healed. Leishmaniasis recidivans often develops on the face, particularly the cheek, with a new ulcer or papule forming over or near the scar of the old lesion. Sometimes this lesion may slowly grow larger.MUCOSAL LEISHMANIASIS
Parasites can spread from the initial skin lesion via the bloodstream to other distant sites such as the mucous membranes of the nose, mouth and throat. Individuals with mucosal leishmaniasis typically have had a skin lesion that healed on its own or with treatment, only to develop mucous membrane involvement often several years or sometimes decades later. Persistent stuffiness in or bleeding from the nose may be the first signs of the disease. Inflammation and partial to total destruction of the mucous membranes of the mouth, nose and throat can eventually occur. If untreated, mucosal leishmaniasis can cause disfiguring damage and scarring to the nose and mouth. Nasal obstruction and bleeding may result from this damage. Complications can be difficult to treat and progressively worsen. Mucosal leishmaniasis can develop in people who were not treated or were originally inadequately treated for cutaneous leishmaniasis. Known risk factors for the development of mucosal disease include infection with particular parasite species often found in South America; skin lesions which are multiple, large, long-lasting or on the head or neck; a suppressed immune system; or infection acquired in Bolivia.VISCERAL LEISHMANIASIS
This form of leishmaniasis, usually the most severe form clinically, also develops if certain parasite species escape from the skin, enter the bloodstream and reach internal organs including the spleen, liver and bone marrow. Clinical findings range from asymptomatic infection to mild disease that resolves on its own to a severe, life-threatening infection. If symptoms develop and the full-blown disease is left untreated, visceral leishmaniasis is usually fatal.Affected individuals may develop repeated bouts of prolonged fever, weakness, unintended weight loss or even severe wasting of the body (cachexia), significant enlargement of the spleen and liver and pancytopenia (low levels of the three main types of blood cells: red blood cells, white blood cells and platelets). A low level of red blood cells is called anemia and can produce fatigue, paleness of the skin (pallor), shortness of breath, lightheadedness, dizziness and a fast or irregular heartbeat. Affected individuals often become progressively worse over weeks to months.Visceral leishmaniasis is also called kala-azar in India. Kala-azar is Hindi for black fever and usually refers to severe, chronic cases of the disease. A variety of additional names can be used for visceral leishmaniasis including Dum-dum fever, Burdwan fever, Sirkari disease and Sahib’s disease.Post-Kala-Azar Dermal Leishmaniasis
This form of infection occurs in people who have or have had visceral leishmaniasis. It is most common in Africa and India. In Africa (e.g., Sudan), the disease is present or noted shortly after diagnosis and treatment for visceral leishmaniasis. Individuals may develop a raised rash on the face, buttocks and arms and legs. These lesions heal on their own over time or following treatment for visceral infection.In India, post-kala-azar dermal leishmaniasis develops several years after treatment for visceral leishmaniasis. Individuals often develop multiple, flat discolored areas of skin (macules). Eventually, these lesions turn into plaques or nodules on the face and trunk. In India, this form requires intensive treatment.Leishmaniasis-HIV Coinfection
Some people are infected by both the human immunodeficiency virus (HIV) and leishmaniasis. These people have a greater chance of developing severe, life-threatening complications and death. They may develop complications not normally seen in otherwise healthy people with leishmaniasis including involvement of the gastrointestinal tract and other atypical sites. Because of HIV-associated immunodeficiency, treatment may be ineffective, and relapse rates are high even after apparently effective treatment.
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Symptoms of Leishmaniasis. Leishmaniasis can affect people in different ways. Some have truly silent infection, and do not develop any signs or symptoms. Other people develop mild to moderate disease, but some develop severe infection which can lead to permanent damage and potentially life-threatening complications.CUTANEOUS LEISHMANIASIS
This is the most common form of leishmaniasis. Symptoms may begin within weeks to months after being bitten by an infected sand fly. Affected individuals may develop one or more sores (skin lesions), particularly on exposed parts of the body such as the face, ears and the arms and legs. The lesions form at the site where the bite occurs. The lesions may be papules (bumps) or nodules (solid, raised bumps), plaques (spread out, raised lesions) or ulcers (open, eroded areas like craters). Skin lesions may change in size, becoming smaller but often enlarge and do not heal. Sores may be moist and leak fluid (like pus) or may be dry and crust over and are usually painless. Individuals may develop lesions that are limited to one area of the body and may slowly heal on their own over 6-18 months. Lesions, however, usually leave noticeable scars. Sometimes, individuals also have swollen, adjacent lymph nodes (lymphadenopathy).Diffuse Cutaneous Leishmaniasis
This very rare form is characterized by an initial skin lesion that spreads to affect the skin of multiple different areas of the body. Individuals often have a poorly functioning immune system, which leaves them susceptible to widespread involvement of the skin, predisposes to a poor response to treatment and permits infection to last indefinitely. Affected individuals may have multiple plaques, ulcers and nodules all over their body. Diffuse cutaneous leishmaniasis progresses slowly but is a chronic condition that routinely recurs after treatment even if treatment appears to have been initially effective.Leishmaniasis Recidivans
This term is used to define the recurrence of a skin lesion years after the initial lesion healed. Leishmaniasis recidivans often develops on the face, particularly the cheek, with a new ulcer or papule forming over or near the scar of the old lesion. Sometimes this lesion may slowly grow larger.MUCOSAL LEISHMANIASIS
Parasites can spread from the initial skin lesion via the bloodstream to other distant sites such as the mucous membranes of the nose, mouth and throat. Individuals with mucosal leishmaniasis typically have had a skin lesion that healed on its own or with treatment, only to develop mucous membrane involvement often several years or sometimes decades later. Persistent stuffiness in or bleeding from the nose may be the first signs of the disease. Inflammation and partial to total destruction of the mucous membranes of the mouth, nose and throat can eventually occur. If untreated, mucosal leishmaniasis can cause disfiguring damage and scarring to the nose and mouth. Nasal obstruction and bleeding may result from this damage. Complications can be difficult to treat and progressively worsen. Mucosal leishmaniasis can develop in people who were not treated or were originally inadequately treated for cutaneous leishmaniasis. Known risk factors for the development of mucosal disease include infection with particular parasite species often found in South America; skin lesions which are multiple, large, long-lasting or on the head or neck; a suppressed immune system; or infection acquired in Bolivia.VISCERAL LEISHMANIASIS
This form of leishmaniasis, usually the most severe form clinically, also develops if certain parasite species escape from the skin, enter the bloodstream and reach internal organs including the spleen, liver and bone marrow. Clinical findings range from asymptomatic infection to mild disease that resolves on its own to a severe, life-threatening infection. If symptoms develop and the full-blown disease is left untreated, visceral leishmaniasis is usually fatal.Affected individuals may develop repeated bouts of prolonged fever, weakness, unintended weight loss or even severe wasting of the body (cachexia), significant enlargement of the spleen and liver and pancytopenia (low levels of the three main types of blood cells: red blood cells, white blood cells and platelets). A low level of red blood cells is called anemia and can produce fatigue, paleness of the skin (pallor), shortness of breath, lightheadedness, dizziness and a fast or irregular heartbeat. Affected individuals often become progressively worse over weeks to months.Visceral leishmaniasis is also called kala-azar in India. Kala-azar is Hindi for black fever and usually refers to severe, chronic cases of the disease. A variety of additional names can be used for visceral leishmaniasis including Dum-dum fever, Burdwan fever, Sirkari disease and Sahib’s disease.Post-Kala-Azar Dermal Leishmaniasis
This form of infection occurs in people who have or have had visceral leishmaniasis. It is most common in Africa and India. In Africa (e.g., Sudan), the disease is present or noted shortly after diagnosis and treatment for visceral leishmaniasis. Individuals may develop a raised rash on the face, buttocks and arms and legs. These lesions heal on their own over time or following treatment for visceral infection.In India, post-kala-azar dermal leishmaniasis develops several years after treatment for visceral leishmaniasis. Individuals often develop multiple, flat discolored areas of skin (macules). Eventually, these lesions turn into plaques or nodules on the face and trunk. In India, this form requires intensive treatment.Leishmaniasis-HIV Coinfection
Some people are infected by both the human immunodeficiency virus (HIV) and leishmaniasis. These people have a greater chance of developing severe, life-threatening complications and death. They may develop complications not normally seen in otherwise healthy people with leishmaniasis including involvement of the gastrointestinal tract and other atypical sites. Because of HIV-associated immunodeficiency, treatment may be ineffective, and relapse rates are high even after apparently effective treatment.
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Causes of Leishmaniasis
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Leishmanial infections are caused by > 20 different species of Leishmania parasites. Parasites are microscopic organisms that live in another organism (called the host, e.g., man) and survive by taking nutrients at the host’s expense. Leishmania are transmitted to humans or animals through the bite of an infected sand fly. Sand flies become infected by biting and sucking the blood of infected people or animals, especially dogs. Sand flies are very small and do not make any noise. Sometimes, their bites can be painful; most often, the bites are painless and go unnoticed. Sand flies are most active from dusk to dawn.Sand flies can bite and infect anyone of any age in areas where leishmaniasis is found. The disease is much more common in rural areas than in cities. There are several risk factors for leishmaniasis, including socioeconomic status (the disease is common to some of the poorest areas on earth), malnutrition and poor housing, and there is some evidence of genetic predisposition. Additional environmental risk factors include deforestation, mining, building damns, changing or creating new irrigation schemes and other aspects of urbanization, which can lead to increased exposure to sand flies and consequently to leishmanial infection. Migratory patterns (the movements of large populations of people susceptible to leishmaniasis) can lead to an increase in the number of people infected.
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Causes of Leishmaniasis. Leishmanial infections are caused by > 20 different species of Leishmania parasites. Parasites are microscopic organisms that live in another organism (called the host, e.g., man) and survive by taking nutrients at the host’s expense. Leishmania are transmitted to humans or animals through the bite of an infected sand fly. Sand flies become infected by biting and sucking the blood of infected people or animals, especially dogs. Sand flies are very small and do not make any noise. Sometimes, their bites can be painful; most often, the bites are painless and go unnoticed. Sand flies are most active from dusk to dawn.Sand flies can bite and infect anyone of any age in areas where leishmaniasis is found. The disease is much more common in rural areas than in cities. There are several risk factors for leishmaniasis, including socioeconomic status (the disease is common to some of the poorest areas on earth), malnutrition and poor housing, and there is some evidence of genetic predisposition. Additional environmental risk factors include deforestation, mining, building damns, changing or creating new irrigation schemes and other aspects of urbanization, which can lead to increased exposure to sand flies and consequently to leishmanial infection. Migratory patterns (the movements of large populations of people susceptible to leishmaniasis) can lead to an increase in the number of people infected.
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Leishmaniasis
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Affects of Leishmaniasis
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Leishmaniasis seldom occurs in the U.S. Most people from the U.S. who become infected do so from travel to or living in regions where the disease is common. Cutaneous infection is periodically reported, however, in Texas and Oklahoma and one case was recently reported further north in North Dakota.The exact number of people who develop leishmaniasis each year in the world is not known. The Centers for Disease Control and Prevention estimates that for cutaneous leishmaniasis, the number of new, clinically apparent cases each year is about 700,000 to 1.2 million people worldwide. For visceral leishmaniasis, the number is about 200,000 to 400,000 cases. More than 90% of people who develop visceral leishmaniasis live in poor rural regions of Bangladesh, Ethiopia, India, Nepal, South Sudan, Sudan and Brazil. Cutaneous leishmaniasis is much more widespread, in South and Central America, the Middle East and Central Asia.
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Affects of Leishmaniasis. Leishmaniasis seldom occurs in the U.S. Most people from the U.S. who become infected do so from travel to or living in regions where the disease is common. Cutaneous infection is periodically reported, however, in Texas and Oklahoma and one case was recently reported further north in North Dakota.The exact number of people who develop leishmaniasis each year in the world is not known. The Centers for Disease Control and Prevention estimates that for cutaneous leishmaniasis, the number of new, clinically apparent cases each year is about 700,000 to 1.2 million people worldwide. For visceral leishmaniasis, the number is about 200,000 to 400,000 cases. More than 90% of people who develop visceral leishmaniasis live in poor rural regions of Bangladesh, Ethiopia, India, Nepal, South Sudan, Sudan and Brazil. Cutaneous leishmaniasis is much more widespread, in South and Central America, the Middle East and Central Asia.
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Related disorders of Leishmaniasis
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There are numerous different infectious diseases, inflammatory conditions, malignant neoplasms and skin conditions that can resemble the signs and symptoms of leishmaniasis.
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Related disorders of Leishmaniasis. There are numerous different infectious diseases, inflammatory conditions, malignant neoplasms and skin conditions that can resemble the signs and symptoms of leishmaniasis.
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Diagnosis of Leishmaniasis
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The diagnosis of leishmaniasis is based upon characteristic symptoms and signs, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A detailed patient history includes whether a person has lived in or traveled to areas where the disease is common. For example, cutaneous leishmaniasis should always be considered with a non-healing or progressive skin lesion in a person who has traveled to or lived in a region where leishmaniasis is found.Clinical Testing and Workup
Doctors take samples of infected tissue to be studied. They may take biopsy or scrapping samples from skin lesions for suspected cutaneous leishmaniasis from lesions in the nose, mouth or throat for suspected mucosal infection, or from the bone marrow (material found within the bones of the body) for suspected visceral leishmaniasis. These samples are sent to laboratories that can examine them in various ways for the presence of Leishmania parasites.Blood tests may be performed to detect antibodies against the Leishmania parasites. Antibodies are specialized proteins created by the immune system in response to foreign or invading pathogens in the body. Doctors readily find antibodies against the Leishmania parasites in the blood of people with visceral leishmaniasis. However, sometimes the test can come back negative even when a person has the disease. Antibody blood tests are not often useful for people with the cutaneous or mucosal forms of leishmaniasis.
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Diagnosis of Leishmaniasis. The diagnosis of leishmaniasis is based upon characteristic symptoms and signs, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. A detailed patient history includes whether a person has lived in or traveled to areas where the disease is common. For example, cutaneous leishmaniasis should always be considered with a non-healing or progressive skin lesion in a person who has traveled to or lived in a region where leishmaniasis is found.Clinical Testing and Workup
Doctors take samples of infected tissue to be studied. They may take biopsy or scrapping samples from skin lesions for suspected cutaneous leishmaniasis from lesions in the nose, mouth or throat for suspected mucosal infection, or from the bone marrow (material found within the bones of the body) for suspected visceral leishmaniasis. These samples are sent to laboratories that can examine them in various ways for the presence of Leishmania parasites.Blood tests may be performed to detect antibodies against the Leishmania parasites. Antibodies are specialized proteins created by the immune system in response to foreign or invading pathogens in the body. Doctors readily find antibodies against the Leishmania parasites in the blood of people with visceral leishmaniasis. However, sometimes the test can come back negative even when a person has the disease. Antibody blood tests are not often useful for people with the cutaneous or mucosal forms of leishmaniasis.
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Therapies of Leishmaniasis
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Treatment
Leishmaniasis is a treatable and curable disease. Specific procedures and therapeutic interventions may vary, depending upon numerous factors, such as the form of the disease (cutaneous, mucosal, visceral); the presence or absence of certain symptoms; geographic location where the person was infected; the specific Leishmania species involved; and an individual’s age and general health. Decisions concerning the use of drug regimens and/or other treatments should be made by physicians experienced in leishmaniasis in consultation with the patient based upon the specifics of his or her case. A thorough discussion of the potential benefits and risks of treatment (including side effects), patient preferences, the potential for scarring in cutaneous infection and other appropriate issues should take place. For example, patients should be clearly informed that initial treatment may be prolonged, more than one course of treatment may be required and given the propensity for relapse in all forms of this infection, that 6-12 months of additional observation after treatment is necessary before considering that “cure” has been achieved.According to the Centers for Disease Control and Prevention (CDC), individuals with cutaneous leishmaniasis may or may not require specific treatment, while all symptomatic, clinically expressed cases of visceral leishmaniasis and mucosal leishmaniasis require treatment. Specific people or groups such as young children, pregnant women, women who are lactating, people with poor functioning immune systems or people with other health conditions may require different medications or different dosage regimens.In 2014, the U.S. Food and Drug Administration (FDA) approved the use of oral miltefosine (Impavido) for the treatment of cutaneous, mucosal and visceral leishmaniasis caused by specific species of Leishmania. This drug should not be used (is contraindicated) in pregnant women.Cutaneous leishmaniasis can heal on its own, although healing can take a long time and often leaves scars. Treatment in specific instances for small, uncomplicated lesions can include applying heat or cold to the sores to destroy the parasites, or an antibiotic known as paromomycin can be applied as an ointment directly onto the sores. Paromomycin is not commercially available in the U.S.For people with cutaneous leishmaniasis who have several large skin lesions, a weakened immune system or infected with Leishmania species that can potentially cause mucosal leishmaniasis, treatment can include various medications such as liposomal amphotericin B, miltefosine or sodium stibogluconate, an antimony-containing drug. In regions outside the U.S., skin lesions are also directly injected with antimonial agents.The best treatment option for mucosal leishmaniasis is not known. Treatments that have been used for this condition are those used in the treatment of visceral infection and include liposomal amphotericin B, miltefosine, and sodium stibogluconate. Surgery may be necessary for people with severe complications of the mucous membranes of the mouth and nose (orofacial surgery).For people with both leishmaniasis and HIV, treatment for HIV infection with antiretroviral therapy may improve the response to antileishmanial treatment, avoid or delay relapses of leishmaniasis and improve overall survival.PreventionPrevention is the most effective means of controlling leishmaniasis. In areas where leishmaniasis is known to be present, steps should be taken to avoid exposure to sand flies, especially from dusk to dawn, by using insect repellent containing DEET and clothing that covers the arms and legs when outside. Travelers should remain in well-screened areas, especially at night when sand flies are most active. Insect screen, netting around the bed, and clothing that is treated with insecticides such as permethrin or pyrethrum should also be used. More information about taking steps to avoid leishmaniasis can be found at the CDC’s traveler’s website (http://wwwnc.cdc.gov/travel).
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Therapies of Leishmaniasis. Treatment
Leishmaniasis is a treatable and curable disease. Specific procedures and therapeutic interventions may vary, depending upon numerous factors, such as the form of the disease (cutaneous, mucosal, visceral); the presence or absence of certain symptoms; geographic location where the person was infected; the specific Leishmania species involved; and an individual’s age and general health. Decisions concerning the use of drug regimens and/or other treatments should be made by physicians experienced in leishmaniasis in consultation with the patient based upon the specifics of his or her case. A thorough discussion of the potential benefits and risks of treatment (including side effects), patient preferences, the potential for scarring in cutaneous infection and other appropriate issues should take place. For example, patients should be clearly informed that initial treatment may be prolonged, more than one course of treatment may be required and given the propensity for relapse in all forms of this infection, that 6-12 months of additional observation after treatment is necessary before considering that “cure” has been achieved.According to the Centers for Disease Control and Prevention (CDC), individuals with cutaneous leishmaniasis may or may not require specific treatment, while all symptomatic, clinically expressed cases of visceral leishmaniasis and mucosal leishmaniasis require treatment. Specific people or groups such as young children, pregnant women, women who are lactating, people with poor functioning immune systems or people with other health conditions may require different medications or different dosage regimens.In 2014, the U.S. Food and Drug Administration (FDA) approved the use of oral miltefosine (Impavido) for the treatment of cutaneous, mucosal and visceral leishmaniasis caused by specific species of Leishmania. This drug should not be used (is contraindicated) in pregnant women.Cutaneous leishmaniasis can heal on its own, although healing can take a long time and often leaves scars. Treatment in specific instances for small, uncomplicated lesions can include applying heat or cold to the sores to destroy the parasites, or an antibiotic known as paromomycin can be applied as an ointment directly onto the sores. Paromomycin is not commercially available in the U.S.For people with cutaneous leishmaniasis who have several large skin lesions, a weakened immune system or infected with Leishmania species that can potentially cause mucosal leishmaniasis, treatment can include various medications such as liposomal amphotericin B, miltefosine or sodium stibogluconate, an antimony-containing drug. In regions outside the U.S., skin lesions are also directly injected with antimonial agents.The best treatment option for mucosal leishmaniasis is not known. Treatments that have been used for this condition are those used in the treatment of visceral infection and include liposomal amphotericin B, miltefosine, and sodium stibogluconate. Surgery may be necessary for people with severe complications of the mucous membranes of the mouth and nose (orofacial surgery).For people with both leishmaniasis and HIV, treatment for HIV infection with antiretroviral therapy may improve the response to antileishmanial treatment, avoid or delay relapses of leishmaniasis and improve overall survival.PreventionPrevention is the most effective means of controlling leishmaniasis. In areas where leishmaniasis is known to be present, steps should be taken to avoid exposure to sand flies, especially from dusk to dawn, by using insect repellent containing DEET and clothing that covers the arms and legs when outside. Travelers should remain in well-screened areas, especially at night when sand flies are most active. Insect screen, netting around the bed, and clothing that is treated with insecticides such as permethrin or pyrethrum should also be used. More information about taking steps to avoid leishmaniasis can be found at the CDC’s traveler’s website (http://wwwnc.cdc.gov/travel).
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Leishmaniasis
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Overview of Lennox-Gastaut Syndrome
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Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that typically becomes apparent during infancy or early childhood. Affected children experience several different types of seizures most commonly atonic, tonic and atypical absence seizures. Children with Lennox-Gastaut syndrome may also develop cognitive dysfunction, delays in reaching developmental milestones and behavioral problems. Lennox-Gastaut syndrome can be caused by a variety of underlying conditions, but in some cases no cause can be identified. Lennox-Gastaut syndrome can be difficult to treat because it is resistant (refractory) to many kinds of antiseizure medications. Research is ongoing to identify and assess new therapies for Lennox-Gastaut syndrome. There is no consensus in the medical literature on the exact definition of Lennox-Gastaut syndrome. Generally, three findings are necessary for the diagnosis: multiple generalized seizure types; a slow spike-and-wave pattern (less than 2.5 Hz) on EEG; and cognitive dysfunction. The International League Against Epilepsy (ILAE) Task Force most recently classified the disorder as an epileptic encephalopathy. Epileptic encephalopathies are a group of disorders in which seizure activity leads to progressive cognitive dysfunction.
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Overview of Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome (LGS) is a severe form of epilepsy that typically becomes apparent during infancy or early childhood. Affected children experience several different types of seizures most commonly atonic, tonic and atypical absence seizures. Children with Lennox-Gastaut syndrome may also develop cognitive dysfunction, delays in reaching developmental milestones and behavioral problems. Lennox-Gastaut syndrome can be caused by a variety of underlying conditions, but in some cases no cause can be identified. Lennox-Gastaut syndrome can be difficult to treat because it is resistant (refractory) to many kinds of antiseizure medications. Research is ongoing to identify and assess new therapies for Lennox-Gastaut syndrome. There is no consensus in the medical literature on the exact definition of Lennox-Gastaut syndrome. Generally, three findings are necessary for the diagnosis: multiple generalized seizure types; a slow spike-and-wave pattern (less than 2.5 Hz) on EEG; and cognitive dysfunction. The International League Against Epilepsy (ILAE) Task Force most recently classified the disorder as an epileptic encephalopathy. Epileptic encephalopathies are a group of disorders in which seizure activity leads to progressive cognitive dysfunction.
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Symptoms of Lennox-Gastaut Syndrome
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The symptoms of Lennox-Gastaut syndrome usually begin during infancy or childhood, most often between 3 to 5 years of age. Multiple types of seizures, which are basically electrical disturbances in the brain, affect children with Lennox-Gastaut syndrome. Most affected individuals experience multiple types of seizures, multiple times throughout the day. As affected individuals grow older, the types and frequency of seizure activity may change.The most common types of seizures associated with Lennox-Gastaut syndrome are tonic and atonic seizures. Tonic seizures cause increased muscle tone and muscle stiffness. They are characterized by sustained muscle contractions that can cause mild abnormalities such as a slight bend of the body and brief interruption of breathing or more significant problems such as muscle spasms of the face and flexion or extension of the arms and legs. Affected children may extend their arms over their heads similar to a ballet dancer. Tonic seizures are usually brief (lasting between a few seconds and a minute) and are especially prevalent at night during sleep, but can also occur during the day. There is usually a brief loss of consciousness during a tonic seizure. Tonic seizures that occur when awake can cause affected individuals to fall.Atonic seizures cause a sudden loss of muscle tone and limpness. They can cause the head to drop or nod, problems with posture or sudden falls. Atonic seizures are also known as drop attacks. Atonic seizures can lead to injuries of the head and face because of sudden, unexpected falls. When sitting, affected individuals may collapsed forward or backward at the waist. Atonic seizures may only partially affect consciousness and usually last only a few seconds.A third type of seizure commonly associated with Lennox-Gastaut syndrome is atypical absence seizures. This type of seizure is associated with a period of unconsciousness usually marked by unresponsive staring. Absence seizures usually begin and end abruptly and the affected individual usually resumes activity with no memory of the episode. Absence seizures do not cause convulsions and may be so mild that they go unnoticed. They usually last only a couple to several seconds. If the child is developmentally delayed, the parents may only notice a subtle change in function or responsiveness.Additional types of seizures can affect individuals with Lennox-Gastaut syndrome less often. These include myoclonic seizures, which are characterized by abnormal, jerky movements and may occur alone or in conjunction with atypical absence seizures; tonic-clonic seizures (once known as grand mal seizures), which last a couple of minutes and are characterized by stiffening of the limbs and then jerking of the limbs and face; and partial or focal seizures, which involve electrical abnormalities in a limited area of the brain and come in a variety of forms. Some individuals with Lennox-Gastaut syndrome experience prolonged, uninterrupted seizure activity that lasts for more than 30 minutes (nonconvulsive status epilepticus). Nonconvulsive status epilepticus may be associated with a child being unaware or inattentive and, in some cases, may be so subtle that it goes unnoticed. Nonconvulsive status epilepticus requires medical intervention.Intelligence is usually, but not always, affected in children with Lennox-Gastaut syndrome. Affected children may experience varying degrees of cognitive dysfunction and delays in reaching developmental milestones such as sitting, crawling or walking. Children with Lennox-Gastaut syndrome may develop normally before the onset of seizures, and then lose previously acquired skills (psychomotor regression).Because the seizures associated with Lennox-Gastaut syndrome are usually resistant to treatment, intellectual impairment and learning problems may worsen over time. Children with Lennox-Gastaut syndrome may also develop behavioral problems ranging from hyperactivity and irritability to autistic symptoms and psychosis.In some cases, individuals with Lennox-Gastaut syndrome may have been initially affected by infantile spasms. Infantile spasms, which are also known as West syndrome, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. (For more on West syndrome, please see the Related Disorders section below.)
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Symptoms of Lennox-Gastaut Syndrome. The symptoms of Lennox-Gastaut syndrome usually begin during infancy or childhood, most often between 3 to 5 years of age. Multiple types of seizures, which are basically electrical disturbances in the brain, affect children with Lennox-Gastaut syndrome. Most affected individuals experience multiple types of seizures, multiple times throughout the day. As affected individuals grow older, the types and frequency of seizure activity may change.The most common types of seizures associated with Lennox-Gastaut syndrome are tonic and atonic seizures. Tonic seizures cause increased muscle tone and muscle stiffness. They are characterized by sustained muscle contractions that can cause mild abnormalities such as a slight bend of the body and brief interruption of breathing or more significant problems such as muscle spasms of the face and flexion or extension of the arms and legs. Affected children may extend their arms over their heads similar to a ballet dancer. Tonic seizures are usually brief (lasting between a few seconds and a minute) and are especially prevalent at night during sleep, but can also occur during the day. There is usually a brief loss of consciousness during a tonic seizure. Tonic seizures that occur when awake can cause affected individuals to fall.Atonic seizures cause a sudden loss of muscle tone and limpness. They can cause the head to drop or nod, problems with posture or sudden falls. Atonic seizures are also known as drop attacks. Atonic seizures can lead to injuries of the head and face because of sudden, unexpected falls. When sitting, affected individuals may collapsed forward or backward at the waist. Atonic seizures may only partially affect consciousness and usually last only a few seconds.A third type of seizure commonly associated with Lennox-Gastaut syndrome is atypical absence seizures. This type of seizure is associated with a period of unconsciousness usually marked by unresponsive staring. Absence seizures usually begin and end abruptly and the affected individual usually resumes activity with no memory of the episode. Absence seizures do not cause convulsions and may be so mild that they go unnoticed. They usually last only a couple to several seconds. If the child is developmentally delayed, the parents may only notice a subtle change in function or responsiveness.Additional types of seizures can affect individuals with Lennox-Gastaut syndrome less often. These include myoclonic seizures, which are characterized by abnormal, jerky movements and may occur alone or in conjunction with atypical absence seizures; tonic-clonic seizures (once known as grand mal seizures), which last a couple of minutes and are characterized by stiffening of the limbs and then jerking of the limbs and face; and partial or focal seizures, which involve electrical abnormalities in a limited area of the brain and come in a variety of forms. Some individuals with Lennox-Gastaut syndrome experience prolonged, uninterrupted seizure activity that lasts for more than 30 minutes (nonconvulsive status epilepticus). Nonconvulsive status epilepticus may be associated with a child being unaware or inattentive and, in some cases, may be so subtle that it goes unnoticed. Nonconvulsive status epilepticus requires medical intervention.Intelligence is usually, but not always, affected in children with Lennox-Gastaut syndrome. Affected children may experience varying degrees of cognitive dysfunction and delays in reaching developmental milestones such as sitting, crawling or walking. Children with Lennox-Gastaut syndrome may develop normally before the onset of seizures, and then lose previously acquired skills (psychomotor regression).Because the seizures associated with Lennox-Gastaut syndrome are usually resistant to treatment, intellectual impairment and learning problems may worsen over time. Children with Lennox-Gastaut syndrome may also develop behavioral problems ranging from hyperactivity and irritability to autistic symptoms and psychosis.In some cases, individuals with Lennox-Gastaut syndrome may have been initially affected by infantile spasms. Infantile spasms, which are also known as West syndrome, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. (For more on West syndrome, please see the Related Disorders section below.)
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Causes of Lennox-Gastaut Syndrome
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In approximately 70-80 percent of patients, Lennox-Gastaut syndrome has an identifiable cause. These cases may be referred to as symptomatic Lennox-Gastaut syndrome. Examples of conditions that can cause Lennox-Gastaut syndrome include abnormal development of the brain cortex (cortical dysplasia), congenital infections, stroke, trauma, reduced oxygen supply that occurs before birth (perinatal hypoxia), infections of the central nervous system such as encephalitis or meningitis and a rare, genetic disorder called tuberous sclerosis. Approximately 17-30 percent of individuals with Lennox-Gastaut syndrome have a previous history of West syndrome. In general, these cases tend to be more severe.Lennox-Gastaut syndrome may also be classified as cryptogenic, in which the cause is unknown or cannot be determined after evaluation. Cryptogenic cases are presumed to result from an unidentified condition (secondary Lennox-Gastaut syndrome). Individuals with cryptogenic Lennox-Gastaut syndrome do not have a previous history of seizure activity, prior neurological problems or cognitive impairment before the development of the disorder. Cryptogenic cases generally have a later onset than symptomatic cases.In some cases of Lennox-Gastaut syndrome no associated condition is present or presumed and the cause of the disorder is unknown.Although the cause of Lennox-Gastaut is known in most cases, the exact underlying mechanisms that ultimately bring about the various seizures that characterize the disorder are unknown. Researchers have not discovered any genes that are associated with Lennox-Gastaut syndrome, although the disorder may have a genetic component that contributes to its development. More research is necessary to determine the specific factors, including any potential genetic factors that are involved in the development of Lennox-Gastaut syndrome.
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Causes of Lennox-Gastaut Syndrome. In approximately 70-80 percent of patients, Lennox-Gastaut syndrome has an identifiable cause. These cases may be referred to as symptomatic Lennox-Gastaut syndrome. Examples of conditions that can cause Lennox-Gastaut syndrome include abnormal development of the brain cortex (cortical dysplasia), congenital infections, stroke, trauma, reduced oxygen supply that occurs before birth (perinatal hypoxia), infections of the central nervous system such as encephalitis or meningitis and a rare, genetic disorder called tuberous sclerosis. Approximately 17-30 percent of individuals with Lennox-Gastaut syndrome have a previous history of West syndrome. In general, these cases tend to be more severe.Lennox-Gastaut syndrome may also be classified as cryptogenic, in which the cause is unknown or cannot be determined after evaluation. Cryptogenic cases are presumed to result from an unidentified condition (secondary Lennox-Gastaut syndrome). Individuals with cryptogenic Lennox-Gastaut syndrome do not have a previous history of seizure activity, prior neurological problems or cognitive impairment before the development of the disorder. Cryptogenic cases generally have a later onset than symptomatic cases.In some cases of Lennox-Gastaut syndrome no associated condition is present or presumed and the cause of the disorder is unknown.Although the cause of Lennox-Gastaut is known in most cases, the exact underlying mechanisms that ultimately bring about the various seizures that characterize the disorder are unknown. Researchers have not discovered any genes that are associated with Lennox-Gastaut syndrome, although the disorder may have a genetic component that contributes to its development. More research is necessary to determine the specific factors, including any potential genetic factors that are involved in the development of Lennox-Gastaut syndrome.
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Affects of Lennox-Gastaut Syndrome
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Lennox-Gastaut syndrome affects males slightly more often than females. Lennox-Gastaut syndrome is estimated to occur in .1-.28 people per 100,000 and is believed to account for 1-4 percent of all cases of childhood epilepsy. The annual incidence in children is estimated to be 2 per 100,000 children. Onset of Lennox-Gastaut syndrome is usually between 2-7 years with a peak onset between 3 to 5 years.
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Affects of Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome affects males slightly more often than females. Lennox-Gastaut syndrome is estimated to occur in .1-.28 people per 100,000 and is believed to account for 1-4 percent of all cases of childhood epilepsy. The annual incidence in children is estimated to be 2 per 100,000 children. Onset of Lennox-Gastaut syndrome is usually between 2-7 years with a peak onset between 3 to 5 years.
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Related disorders of Lennox-Gastaut Syndrome
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Symptoms of the following disorders can be similar to those of Lennox-Gastaut syndrome. Comparisons may be useful for a differential diagnosis.West syndrome is a type of epilepsy characterized by spasms, an abnormal brain wave pattern (interictal EEG) called hypsarrhythmia and cognitive dysfunction. The spasms that occur may range from violent jackknife or “salaam” movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. There are many different causes of West syndrome and if a specific cause can be identified, a diagnosis of symptomatic West syndrome can be made. If a cause cannot be determined, a diagnosis of cryptogenic West syndrome is made. Some infants with West syndrome may eventually develop Lennox-Gestaut syndrome. (For more information on this disorder, choose “West” as your search term in the Rare Disease Database.)Epilepsy is a general term for a group of neurological disorders characterized by recurrent seizures, and associated with abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks may be preceded by an “aura”, a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. This is typically in partial-onset seizures. There are many different types of epilepsy and the exact cause is generally unknown. Epilepsy can also occur as part of larger syndromes. Types of epilepsy or disorders associated with epilepsy include Rett syndrome, Angleman syndrome, Landau-Kleffner syndrome, Dravet syndrome, and the neuronal ceroid lipofuscinoses. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of Lennox-Gastaut Syndrome. Symptoms of the following disorders can be similar to those of Lennox-Gastaut syndrome. Comparisons may be useful for a differential diagnosis.West syndrome is a type of epilepsy characterized by spasms, an abnormal brain wave pattern (interictal EEG) called hypsarrhythmia and cognitive dysfunction. The spasms that occur may range from violent jackknife or “salaam” movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. There are many different causes of West syndrome and if a specific cause can be identified, a diagnosis of symptomatic West syndrome can be made. If a cause cannot be determined, a diagnosis of cryptogenic West syndrome is made. Some infants with West syndrome may eventually develop Lennox-Gestaut syndrome. (For more information on this disorder, choose “West” as your search term in the Rare Disease Database.)Epilepsy is a general term for a group of neurological disorders characterized by recurrent seizures, and associated with abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks may be preceded by an “aura”, a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. This is typically in partial-onset seizures. There are many different types of epilepsy and the exact cause is generally unknown. Epilepsy can also occur as part of larger syndromes. Types of epilepsy or disorders associated with epilepsy include Rett syndrome, Angleman syndrome, Landau-Kleffner syndrome, Dravet syndrome, and the neuronal ceroid lipofuscinoses. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Lennox-Gastaut Syndrome
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Diagnosis of Lennox-Gastaut Syndrome
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Lennox-Gastaut syndrome is defined as having a clinical triad that must be identified for a diagnosis. This triad consists of multiple seizures of different types, a distinctive EEG brain wave pattern (slow [1.5- to 2.5-Hz] spike-and-wave pattern)(Note this pattern may not be present on every EEG.) and some degree of cognitive impairment and behavioral abnormalities. However, these symptoms may not all be present at the onset of the disorder, making an accurate diagnosis of Lennox-Gastaut syndrome difficult. The wide variety of potential causes of Lennox-Gastaut syndrome also complicates the diagnosis.A diagnosis of Lennox-Gastaut syndrome is usually made based upon a thorough clinical evaluation, a detailed patient history and a complete physical and neurological evaluation including advanced imaging techniques, such as electroencephalography (EEG) and magnetic resonance imaging (MRI). During an EEG, the brain’s electrical impulses are recorded. In individuals with LGS, such EEG testing typically reveals the distinctive brain wave pattern (slow [1.5- to 2.5-Hz] spike-and-wave pattern). During a MRI scan, three-dimensional images are produced that reflect the brain’s anatomy; such scanning helps physicians examine brain structure and potentially locate the cause of the seizure activity. Epilepsy gene panels that assay for multiple genetic causes are starting to become part of the evaluation process.
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Diagnosis of Lennox-Gastaut Syndrome. Lennox-Gastaut syndrome is defined as having a clinical triad that must be identified for a diagnosis. This triad consists of multiple seizures of different types, a distinctive EEG brain wave pattern (slow [1.5- to 2.5-Hz] spike-and-wave pattern)(Note this pattern may not be present on every EEG.) and some degree of cognitive impairment and behavioral abnormalities. However, these symptoms may not all be present at the onset of the disorder, making an accurate diagnosis of Lennox-Gastaut syndrome difficult. The wide variety of potential causes of Lennox-Gastaut syndrome also complicates the diagnosis.A diagnosis of Lennox-Gastaut syndrome is usually made based upon a thorough clinical evaluation, a detailed patient history and a complete physical and neurological evaluation including advanced imaging techniques, such as electroencephalography (EEG) and magnetic resonance imaging (MRI). During an EEG, the brain’s electrical impulses are recorded. In individuals with LGS, such EEG testing typically reveals the distinctive brain wave pattern (slow [1.5- to 2.5-Hz] spike-and-wave pattern). During a MRI scan, three-dimensional images are produced that reflect the brain’s anatomy; such scanning helps physicians examine brain structure and potentially locate the cause of the seizure activity. Epilepsy gene panels that assay for multiple genetic causes are starting to become part of the evaluation process.
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Lennox-Gastaut Syndrome
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Therapies of Lennox-Gastaut Syndrome
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Treatment
No specific therapy for Lennox-Gastaut syndrome is effective in all cases and the disorder has proven particularly resistant to most therapeutic options. The three main forms of treatment of Lennox-Gastaut syndrome are anti-epileptic drugs (AEDs), dietary therapy (typically the ketogenic diet) or device/surgery (VNS therapy or corpus callosotomy). Rarely, resective surgery is an option.Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, pediatric neurologists, surgeons, and/or other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Families need to work with healthcare professionals to develop a treatment plan that covers various potential situations such as seizure emergencies, routine medical illnesses, or what to do if an affected individual misses a dosage of medication. Families should also keep a list of which medications can possibly worsen Lennox-Gastaut syndrome. An affected individual’s treatment regimen will need repeated revisions throughout a person’s life as the types and frequency of seizures may change and the effectiveness of a particular therapy can lessen. Other healthcare providers are frequently consulted, including social workers, neuropsychologists, psychiatrists and rehabilitation services (occupational, physical and speech therapy).AEDs are usually given to individuals with Lennox-Gastaut syndrome, but the individual response is highly variable. In some cases, it is possible that treatment with AEDs may help reduce or control various types of seizure activity associated with LGS. However, because individuals with Lennox-Gastaut syndrome have different types of seizures, they often require therapy with multiple types of AEDs. Such medications may include clonazepam, sodium valproate, topiramate, lamotrigine, felbamate (closely monitored), clobazam,rufinamide or cannabidiol. However, such drugs may have limited success in treating seizure activity in some individuals with the disorder. In addition, AEDs may be associated with significant side effects, especially in individuals who receive multidrug, high-dose regimens. AEDs can also become less effective over time. Being on multiple medications, which may cause sedation, can sometimes worsen seizure control.Valproate (valproic acid) is generally considered the first-line therapy for Lennox-Gastaut syndrome because it is effective against a wide spectrum of seizures. Valproate is usually first given alone (monotherapy) and if ineffective another drug such as lamotrigine, topiramate, rufinamide, clobazam or cannabidiol may be added.A variety of specific drugs have been approved by the Food and Drug Administration (FDA) for the treatment of Lennox-Gastaut syndrome including topiramate (Topamax). Topiramate has been approved as an add-on (adjunctive) therapy for children and adults. The drug is manufactured by Ortho-McNeil Neurologics.The FDA has also approved the anticonvulsant drug felbamate (Felbatol) for the treatment of seizures in children with Lennox-Gastaut syndrome. Due to the occurrence of rare but serious side effects from the drug, physicians should become familiar with the medication and know how to monitor for side-effects before prescribing the medication. This drug, while effective, is not typically first or second line because of the side-effect concerns. The drug is manufactured by Meda Pharmaceuticals, Inc.In addition, the FDA has approved the lamotrigine (Lamictal) as an add-on (adjunctive) therapy (i.e., as a medication to be used in association with other appropriate anticonvulsant medications) for the treatment of generalized seizures associated with Lennox-Gastaut syndrome. For more information, contact GlaxoSmithKline Inc.In 2008, the FDA approved rufinamide (Banzel) for the use as an adjunctive (add-on) treatment for seizures associated with Lennox-Gastaut syndrome. Rufinamide decreases seizure frequency in some individuals and seems to be particularly effective for atonic or drop attack seizures. Banzel is manufactured by Eisai Inc.Clobazam (Onfi) was approved by the FDA in 2011 to treat the seizures associated with Lennox-Gastaut syndrome. Onfi is manufactured by Catalent Pharma Solutions LLC for Lundbeck.In 2018, Epidiolex (cannabidiol or CBD) was approved to treat seizures associated with Lennox-Gastaut syndrome in patients two years of age and older. This is the first FDA-approved drug that contains a purified drug substance derived from the Cannabis plant. Epidiolex is manufactured by Greenwich Biosciences.Additional therapies that have been used to treat individuals with Lennox-Gastaut syndrome include the ketogenic diet, VNS Therapy and various surgical techniques. These options are generally reserved for individuals who have been treated with at least 2 – 3 approved medications without an adequate response, and are typically combined with drug therapy (The exception is dietary therapy, which is typically added to drug therapy, but rarely maybe successful by itself in this population.).The ketogenic diet may reduce seizure activity in some individuals with Lennox-Gastaut syndrome. The ketogenic diet is a high fat, low carbohydrate diet that makes the body burn fat for energy instead of sugar (glucose). It is a strict diet that requires rigid compliance and commitment. The ketogenic diet can have side effects and individuals following the diet should be routinely monitored by their physicians and a trained nutritionist. The effectiveness of the ketogenic diet varies from one individual to another. Researchers do not understand why the diet is effective in treating seizures or why it is effective for some people, but not others.Some individuals with Lennox-Gastaut syndrome, especially those who have not responded to other forms of therapy, may be treated with surgical therapies including complete corpus callosotomy or vagus nerve stimulation.A corpus callosotomy is a surgical procedure in which the cerebral hemispheres are disconnected by cutting the corpus callosum, which is a large bundle of nerves that connects the two halves (hemispheres) of the brain and allows them to share information. This procedure does not include the cutting of brain tissue. This procedure is generally reserved for individuals who suffer from intractable seizures that lead to injuries (e.g., drop seizures or frequent generalized tonic-clonic seizures) or are potentially life-threatening. It is most effective for atonic, tonic and tonic-clonic seizures.Vagus nerve stimulation is a procedure in which a device called a pulse generator is inserted into the chest and a wire is run underneath the skin to the vagus nerve in the neck. The pulse generator is similar to a pacemaker and transmits mild, electrical impulses to the brain via the vagus nerve. These impulses prevent seizures from occurring. The intensity and timing of the nerve impulses are determined based upon each individual’s needs. This is combined with drug therapy and most effective for drop seizures and generalized tonic-clonic seizures.
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Therapies of Lennox-Gastaut Syndrome. Treatment
No specific therapy for Lennox-Gastaut syndrome is effective in all cases and the disorder has proven particularly resistant to most therapeutic options. The three main forms of treatment of Lennox-Gastaut syndrome are anti-epileptic drugs (AEDs), dietary therapy (typically the ketogenic diet) or device/surgery (VNS therapy or corpus callosotomy). Rarely, resective surgery is an option.Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, pediatric neurologists, surgeons, and/or other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Families need to work with healthcare professionals to develop a treatment plan that covers various potential situations such as seizure emergencies, routine medical illnesses, or what to do if an affected individual misses a dosage of medication. Families should also keep a list of which medications can possibly worsen Lennox-Gastaut syndrome. An affected individual’s treatment regimen will need repeated revisions throughout a person’s life as the types and frequency of seizures may change and the effectiveness of a particular therapy can lessen. Other healthcare providers are frequently consulted, including social workers, neuropsychologists, psychiatrists and rehabilitation services (occupational, physical and speech therapy).AEDs are usually given to individuals with Lennox-Gastaut syndrome, but the individual response is highly variable. In some cases, it is possible that treatment with AEDs may help reduce or control various types of seizure activity associated with LGS. However, because individuals with Lennox-Gastaut syndrome have different types of seizures, they often require therapy with multiple types of AEDs. Such medications may include clonazepam, sodium valproate, topiramate, lamotrigine, felbamate (closely monitored), clobazam,rufinamide or cannabidiol. However, such drugs may have limited success in treating seizure activity in some individuals with the disorder. In addition, AEDs may be associated with significant side effects, especially in individuals who receive multidrug, high-dose regimens. AEDs can also become less effective over time. Being on multiple medications, which may cause sedation, can sometimes worsen seizure control.Valproate (valproic acid) is generally considered the first-line therapy for Lennox-Gastaut syndrome because it is effective against a wide spectrum of seizures. Valproate is usually first given alone (monotherapy) and if ineffective another drug such as lamotrigine, topiramate, rufinamide, clobazam or cannabidiol may be added.A variety of specific drugs have been approved by the Food and Drug Administration (FDA) for the treatment of Lennox-Gastaut syndrome including topiramate (Topamax). Topiramate has been approved as an add-on (adjunctive) therapy for children and adults. The drug is manufactured by Ortho-McNeil Neurologics.The FDA has also approved the anticonvulsant drug felbamate (Felbatol) for the treatment of seizures in children with Lennox-Gastaut syndrome. Due to the occurrence of rare but serious side effects from the drug, physicians should become familiar with the medication and know how to monitor for side-effects before prescribing the medication. This drug, while effective, is not typically first or second line because of the side-effect concerns. The drug is manufactured by Meda Pharmaceuticals, Inc.In addition, the FDA has approved the lamotrigine (Lamictal) as an add-on (adjunctive) therapy (i.e., as a medication to be used in association with other appropriate anticonvulsant medications) for the treatment of generalized seizures associated with Lennox-Gastaut syndrome. For more information, contact GlaxoSmithKline Inc.In 2008, the FDA approved rufinamide (Banzel) for the use as an adjunctive (add-on) treatment for seizures associated with Lennox-Gastaut syndrome. Rufinamide decreases seizure frequency in some individuals and seems to be particularly effective for atonic or drop attack seizures. Banzel is manufactured by Eisai Inc.Clobazam (Onfi) was approved by the FDA in 2011 to treat the seizures associated with Lennox-Gastaut syndrome. Onfi is manufactured by Catalent Pharma Solutions LLC for Lundbeck.In 2018, Epidiolex (cannabidiol or CBD) was approved to treat seizures associated with Lennox-Gastaut syndrome in patients two years of age and older. This is the first FDA-approved drug that contains a purified drug substance derived from the Cannabis plant. Epidiolex is manufactured by Greenwich Biosciences.Additional therapies that have been used to treat individuals with Lennox-Gastaut syndrome include the ketogenic diet, VNS Therapy and various surgical techniques. These options are generally reserved for individuals who have been treated with at least 2 – 3 approved medications without an adequate response, and are typically combined with drug therapy (The exception is dietary therapy, which is typically added to drug therapy, but rarely maybe successful by itself in this population.).The ketogenic diet may reduce seizure activity in some individuals with Lennox-Gastaut syndrome. The ketogenic diet is a high fat, low carbohydrate diet that makes the body burn fat for energy instead of sugar (glucose). It is a strict diet that requires rigid compliance and commitment. The ketogenic diet can have side effects and individuals following the diet should be routinely monitored by their physicians and a trained nutritionist. The effectiveness of the ketogenic diet varies from one individual to another. Researchers do not understand why the diet is effective in treating seizures or why it is effective for some people, but not others.Some individuals with Lennox-Gastaut syndrome, especially those who have not responded to other forms of therapy, may be treated with surgical therapies including complete corpus callosotomy or vagus nerve stimulation.A corpus callosotomy is a surgical procedure in which the cerebral hemispheres are disconnected by cutting the corpus callosum, which is a large bundle of nerves that connects the two halves (hemispheres) of the brain and allows them to share information. This procedure does not include the cutting of brain tissue. This procedure is generally reserved for individuals who suffer from intractable seizures that lead to injuries (e.g., drop seizures or frequent generalized tonic-clonic seizures) or are potentially life-threatening. It is most effective for atonic, tonic and tonic-clonic seizures.Vagus nerve stimulation is a procedure in which a device called a pulse generator is inserted into the chest and a wire is run underneath the skin to the vagus nerve in the neck. The pulse generator is similar to a pacemaker and transmits mild, electrical impulses to the brain via the vagus nerve. These impulses prevent seizures from occurring. The intensity and timing of the nerve impulses are determined based upon each individual’s needs. This is combined with drug therapy and most effective for drop seizures and generalized tonic-clonic seizures.
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Lennox-Gastaut Syndrome
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nord_709_0
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Overview of Lenz Microphthalmia Syndrome
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Lenz microphthalmia syndrome is an extremely rare inherited disorder characterized by small eyes (microphthalmos or microphthalmia) and/or droopy eyelids (blepharoptosis), resulting in visual impairment. Rarely, affected infants may exhibit complete absence of the eyes (anophthalmos or anophthalmia). Additional physical anomalies are often associated, including a small head (microcephaly) and/or anomalies of the teeth, ears and/or fingers and/or toes (digits). The range and severity of findings may vary from person to person. Most affected children also exhibit developmental delays and intellectual disability.Lenz microphthalmia syndrome is caused by pathogenic variants, or changes, in the BCOR gene and is inherited in an X-linked pattern. This condition is fully expressed in males only. However, females who carry a variant BCOR gene may exhibit some symptoms, such as microcephaly, short stature and/or anomalies of the fingers and/or toes.
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Overview of Lenz Microphthalmia Syndrome. Lenz microphthalmia syndrome is an extremely rare inherited disorder characterized by small eyes (microphthalmos or microphthalmia) and/or droopy eyelids (blepharoptosis), resulting in visual impairment. Rarely, affected infants may exhibit complete absence of the eyes (anophthalmos or anophthalmia). Additional physical anomalies are often associated, including a small head (microcephaly) and/or anomalies of the teeth, ears and/or fingers and/or toes (digits). The range and severity of findings may vary from person to person. Most affected children also exhibit developmental delays and intellectual disability.Lenz microphthalmia syndrome is caused by pathogenic variants, or changes, in the BCOR gene and is inherited in an X-linked pattern. This condition is fully expressed in males only. However, females who carry a variant BCOR gene may exhibit some symptoms, such as microcephaly, short stature and/or anomalies of the fingers and/or toes.
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Lenz Microphthalmia Syndrome
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Symptoms of Lenz Microphthalmia Syndrome
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In affected males, the primary physical characteristic associated with Lenz microphthalmia syndrome is small eyes (one eye or both). In most cases, both eyes are affected and the eyes maybe of different size (bilateral, asymmetrical microphthalmos/microphthalmia). The front (anterior), clear portion of the eye through which light passes (cornea) may be small (microcornea). In addition, the colored portion of the eye (iris) may be differently formed with absent tissue (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other parts of the eye, including the ciliary body, choroid and/or optic disc. In many patients, the upper eyelids may droop (blepharoptosis) due to paralysis of muscles that control the eyelids. In rare cases, affected infants may exhibit absence or only rudimentary (vestigial) portions of the eyes (anophthalmos/anophthalmia). Such eye findings may result in varying degrees of visual impairment or, in some people, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.Affected males may exhibit mild to severe delays in attaining certain developmental milestones (e.g., crawling, sitting independently, walking, etc.) and intellectual disability ranging from mild to severe.Most infants with Lenz microphthalmia syndrome also exhibit additional physical findings, such as anomalies of the head and facial (craniofacial) area. These usually include a small head (microcephaly) and anomalies of the ears and teeth. In most infants with this disorder, the ears are flexed forward (anteverted), and the ear lobes may be large; however, in some children, the ears may also be small and underdeveloped (hypoplastic). Hearing impairment may be present in some people. The teeth may be widely spaced or abnormally crowded. In addition, the front teeth (incisors) may be absent (dental agenesis or anodontia) or malformed. Some affected males may exhibit incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove or incomplete closure of the upper lip (cleft lip). Most males with the disorder also have skeletal anomalies. These may include a lateral (sideways) and front-to-back (anterior-posterior) curvature of the spine (kyphoscoliosis), narrow and/or sloping shoulders, underdeveloped collarbones (hypoplastic clavicles) and/or a differently shaped rib cage (thoracic cage).In addition, infants with Lenz microphthalmia syndrome often exhibit anomalies of the fingers and/or toes (digits). The digits may be bent (clinodactyly), flexed (camptodactyly) and/or joined (syndactyly). In some people, double thumbs may also be present.Approximately half of affected males may also have abnormalities of the reproductive and urinary (genitourinary) systems. These malformations may include failure of the testes to descend into the scrotum (cryptorchidism), placement of the urinary opening (meatus) on the underside of the penis (hypospadias) and/or underdevelopment (hypoplasia) or absence (agenesis) of a kidney (renal agenesis).Females who carry a single variant in the gene for Lenz microphthalmia syndrome (heterozygous carriers) may exhibit some of the symptoms associated with the disease. In this situation, the symptoms are typically milder than those associated with the fully expressed disorder in males. Heterozygous females may have anomalies in the fingers and/or toes (digital anomalies), a small head (microcephaly) and/or short stature.
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Symptoms of Lenz Microphthalmia Syndrome. In affected males, the primary physical characteristic associated with Lenz microphthalmia syndrome is small eyes (one eye or both). In most cases, both eyes are affected and the eyes maybe of different size (bilateral, asymmetrical microphthalmos/microphthalmia). The front (anterior), clear portion of the eye through which light passes (cornea) may be small (microcornea). In addition, the colored portion of the eye (iris) may be differently formed with absent tissue (coloboma), giving the iris a “keyhole” appearance. Colobomas may also affect other parts of the eye, including the ciliary body, choroid and/or optic disc. In many patients, the upper eyelids may droop (blepharoptosis) due to paralysis of muscles that control the eyelids. In rare cases, affected infants may exhibit absence or only rudimentary (vestigial) portions of the eyes (anophthalmos/anophthalmia). Such eye findings may result in varying degrees of visual impairment or, in some people, blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.Affected males may exhibit mild to severe delays in attaining certain developmental milestones (e.g., crawling, sitting independently, walking, etc.) and intellectual disability ranging from mild to severe.Most infants with Lenz microphthalmia syndrome also exhibit additional physical findings, such as anomalies of the head and facial (craniofacial) area. These usually include a small head (microcephaly) and anomalies of the ears and teeth. In most infants with this disorder, the ears are flexed forward (anteverted), and the ear lobes may be large; however, in some children, the ears may also be small and underdeveloped (hypoplastic). Hearing impairment may be present in some people. The teeth may be widely spaced or abnormally crowded. In addition, the front teeth (incisors) may be absent (dental agenesis or anodontia) or malformed. Some affected males may exhibit incomplete closure of the roof of the mouth (cleft palate) and/or a vertical groove or incomplete closure of the upper lip (cleft lip). Most males with the disorder also have skeletal anomalies. These may include a lateral (sideways) and front-to-back (anterior-posterior) curvature of the spine (kyphoscoliosis), narrow and/or sloping shoulders, underdeveloped collarbones (hypoplastic clavicles) and/or a differently shaped rib cage (thoracic cage).In addition, infants with Lenz microphthalmia syndrome often exhibit anomalies of the fingers and/or toes (digits). The digits may be bent (clinodactyly), flexed (camptodactyly) and/or joined (syndactyly). In some people, double thumbs may also be present.Approximately half of affected males may also have abnormalities of the reproductive and urinary (genitourinary) systems. These malformations may include failure of the testes to descend into the scrotum (cryptorchidism), placement of the urinary opening (meatus) on the underside of the penis (hypospadias) and/or underdevelopment (hypoplasia) or absence (agenesis) of a kidney (renal agenesis).Females who carry a single variant in the gene for Lenz microphthalmia syndrome (heterozygous carriers) may exhibit some of the symptoms associated with the disease. In this situation, the symptoms are typically milder than those associated with the fully expressed disorder in males. Heterozygous females may have anomalies in the fingers and/or toes (digital anomalies), a small head (microcephaly) and/or short stature.
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Lenz Microphthalmia Syndrome
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Causes of Lenz Microphthalmia Syndrome
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Lenz microphthalmia syndrome is caused by changes or pathogenic variants in the BCOR gene and is inherited in an X-linked pattern. Some researchers speculate that severe cases of Lenz microphthalmia syndrome may result from deletions of genetic material from two or more adjacent genes (contiguous gene syndrome) located on the X chromosome.X-linked genetic disorders are conditions caused by a non-working (non-functional) gene on the X chromosome and typically manifest mostly in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not usually display symptoms because females have two X chromosomes and only one carries the non-working gene. However, some carrier females may exhibit some of the symptoms associated with the disorder as mentioned above. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene, he will develop the disease.Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
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Causes of Lenz Microphthalmia Syndrome. Lenz microphthalmia syndrome is caused by changes or pathogenic variants in the BCOR gene and is inherited in an X-linked pattern. Some researchers speculate that severe cases of Lenz microphthalmia syndrome may result from deletions of genetic material from two or more adjacent genes (contiguous gene syndrome) located on the X chromosome.X-linked genetic disorders are conditions caused by a non-working (non-functional) gene on the X chromosome and typically manifest mostly in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not usually display symptoms because females have two X chromosomes and only one carries the non-working gene. However, some carrier females may exhibit some of the symptoms associated with the disorder as mentioned above. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working gene, he will develop the disease.Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
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Lenz Microphthalmia Syndrome
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Affects of Lenz Microphthalmia Syndrome
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Approximately 12 affected males with fully expressed Lenz microphthalmia syndrome have been reported in the medical literature.
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Affects of Lenz Microphthalmia Syndrome. Approximately 12 affected males with fully expressed Lenz microphthalmia syndrome have been reported in the medical literature.
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Lenz Microphthalmia Syndrome
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Related disorders of Lenz Microphthalmia Syndrome
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Symptoms of the following disorders can be similar to those of Lenz microphthalmia syndrome. For more information on each of these disorders, enter the disease name as your search term in the Rare Disease Database.Nance-Horan syndrome
Oculo-dento-digital dysplasia
Chromosome 10, partial distal trisomy 10q.There are many other disorders that are characterized by microphthalmia or anophthalmia occurring in association with absence of eye tissue (colobomas) in certain parts of the eye; other eye anomalies; anomalies of the ears, mouth, and/or teeth; digital anomalies; developmental and/or intellectual disability; and/or other abnormalities similar to those associated with Lenz microphthalmia syndrome.
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Related disorders of Lenz Microphthalmia Syndrome. Symptoms of the following disorders can be similar to those of Lenz microphthalmia syndrome. For more information on each of these disorders, enter the disease name as your search term in the Rare Disease Database.Nance-Horan syndrome
Oculo-dento-digital dysplasia
Chromosome 10, partial distal trisomy 10q.There are many other disorders that are characterized by microphthalmia or anophthalmia occurring in association with absence of eye tissue (colobomas) in certain parts of the eye; other eye anomalies; anomalies of the ears, mouth, and/or teeth; digital anomalies; developmental and/or intellectual disability; and/or other abnormalities similar to those associated with Lenz microphthalmia syndrome.
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Lenz Microphthalmia Syndrome
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Diagnosis of Lenz Microphthalmia Syndrome
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The diagnosis of Lenz microphthalmia syndrome may be confirmed at birth, based upon a thorough clinical evaluation, characteristic physical findings and imaging techniques. Ultrasonography studies of the internal structure of the eye may demonstrate that the length from the front to the back of the eye (anteroposterior axis) is smaller than normal, confirming a diagnosis of microphthalmia. In some people, however, it may be difficult to distinguish severe microphthalmia from anophthalmia. Therefore, ultrasound imaging or magnetic resonance imaging (MRI) may sometimes be used to help confirm which condition is present. When MRI scanning is unable to clarify which malformation is present, other diagnostic steps may sometimes be taken to determine whether rudimentary (vestigial) portions of the eyes are present or absent.Additional diagnostic steps may also be taken to confirm the presence of other physical findings typically associated with Lenz microphthalmia syndrome. Examination with an instrument that visualizes the interior of the eye (ophthalmoscopy) may be used to determine the absence of ocular tissue in the eye (colobomas). Drooping of the upper eyelid (blepharoptosis) may be diagnosed by clinical evaluation, including comparison with the other eyelid (if the anomaly affects only one side) or examination of the infant's upper gaze. Imaging techniques may confirm the presence of dental, skeletal, genitourinary and/or other anomalies associated with Lenz microphthalmia syndrome.In some familial cases, Lenz microphthalmia syndrome may be detected before birth (prenatally). For example, ultrasound studies during pregnancy may reveal characteristic findings suggestive of Lenz microphthalmia syndrome in siblings of affected children.
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Diagnosis of Lenz Microphthalmia Syndrome. The diagnosis of Lenz microphthalmia syndrome may be confirmed at birth, based upon a thorough clinical evaluation, characteristic physical findings and imaging techniques. Ultrasonography studies of the internal structure of the eye may demonstrate that the length from the front to the back of the eye (anteroposterior axis) is smaller than normal, confirming a diagnosis of microphthalmia. In some people, however, it may be difficult to distinguish severe microphthalmia from anophthalmia. Therefore, ultrasound imaging or magnetic resonance imaging (MRI) may sometimes be used to help confirm which condition is present. When MRI scanning is unable to clarify which malformation is present, other diagnostic steps may sometimes be taken to determine whether rudimentary (vestigial) portions of the eyes are present or absent.Additional diagnostic steps may also be taken to confirm the presence of other physical findings typically associated with Lenz microphthalmia syndrome. Examination with an instrument that visualizes the interior of the eye (ophthalmoscopy) may be used to determine the absence of ocular tissue in the eye (colobomas). Drooping of the upper eyelid (blepharoptosis) may be diagnosed by clinical evaluation, including comparison with the other eyelid (if the anomaly affects only one side) or examination of the infant's upper gaze. Imaging techniques may confirm the presence of dental, skeletal, genitourinary and/or other anomalies associated with Lenz microphthalmia syndrome.In some familial cases, Lenz microphthalmia syndrome may be detected before birth (prenatally). For example, ultrasound studies during pregnancy may reveal characteristic findings suggestive of Lenz microphthalmia syndrome in siblings of affected children.
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Lenz Microphthalmia Syndrome
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Therapies of Lenz Microphthalmia Syndrome
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Treatment
The treatment of Lenz microphthalmia 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, physicians who diagnose and treat diseases of the eye (ophthalmologists); dental specialists who diagnose, prevent, and/or correct anomalies of the teeth (orthodontists); specialists who diagnose and treat skeletal anomalies (orthopedists); and/or others may need to work together to ensure a comprehensive approach to treatment.Specific therapies for the treatment of Lenz microphthalmia syndrome are symptomatic and supportive. In some patients, corrective glasses, contact lenses and/or surgery may be used to help improve vision. Artificial teeth (dentures), dental implants, braces, dental surgery and/or other corrective procedures may be undertaken to correct dental anomalies. Differences in curvature of the spine (kyphoscoliosis) may be treated with a combination of exercises and physical therapy, other supportive techniques, braces, casts, and/or corrective surgery. Surgery may also be performed to correct cleft lip and palate; digital, skeletal and/or genitourinary malformations or other anomalies associated with the disorder.Early intervention is important to ensure that children with Lenz microphthalmia syndrome reach their potential. Special services that may be beneficial to affected children may include special education and other medical, social and/or vocational services.Genetic counseling is recommended for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Lenz microphthalmia syndrome. Other treatment for is symptomatic and supportive.
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Therapies of Lenz Microphthalmia Syndrome. Treatment
The treatment of Lenz microphthalmia 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, physicians who diagnose and treat diseases of the eye (ophthalmologists); dental specialists who diagnose, prevent, and/or correct anomalies of the teeth (orthodontists); specialists who diagnose and treat skeletal anomalies (orthopedists); and/or others may need to work together to ensure a comprehensive approach to treatment.Specific therapies for the treatment of Lenz microphthalmia syndrome are symptomatic and supportive. In some patients, corrective glasses, contact lenses and/or surgery may be used to help improve vision. Artificial teeth (dentures), dental implants, braces, dental surgery and/or other corrective procedures may be undertaken to correct dental anomalies. Differences in curvature of the spine (kyphoscoliosis) may be treated with a combination of exercises and physical therapy, other supportive techniques, braces, casts, and/or corrective surgery. Surgery may also be performed to correct cleft lip and palate; digital, skeletal and/or genitourinary malformations or other anomalies associated with the disorder.Early intervention is important to ensure that children with Lenz microphthalmia syndrome reach their potential. Special services that may be beneficial to affected children may include special education and other medical, social and/or vocational services.Genetic counseling is recommended for affected individuals and their families. Family members of affected individuals should also receive regular clinical evaluations to detect any symptoms and physical characteristics that may be potentially associated with Lenz microphthalmia syndrome. Other treatment for is symptomatic and supportive.
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Lenz Microphthalmia Syndrome
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Overview of LEPR Deficiency
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Summary LEPR deficiency is a rare, inherited condition that affects how the body processes energy, responds to food and stores fat. Most people with this condition are obese before one year of age. Other symptoms include constant hunger and abnormal behaviors related to food. People affected with LEPR deficiency have low levels of sex hormones (hypogonadotropic hypogonadism) resulting in late or absent puberty and infertility. LEPR deficiency is caused by changes (mutations or variants) in the LEPR gene, which is responsible for making the receptor that interacts with a protein called leptin. Leptin is important for regulating appetite and growth of body fat. This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Diet, behavior modification, exercise programs and bariatric surgery have been used to help manage the symptoms of LEPR deficiency. Treatment is available for this condition using a drug called setmelanotide. With treatment, people with LEPR deficiency develop a normal appetite, lose weight and fat and can maintain the weight loss.IntroductionLEPR deficiency is rare, making it difficult to predict exactly how it will affect someone who is newly diagnosed with this condition. It is one of several conditions that include early-onset obesity and these conditions can be difficult to distinguish from each other without a careful physical examination and genetic testing.
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Overview of LEPR Deficiency. Summary LEPR deficiency is a rare, inherited condition that affects how the body processes energy, responds to food and stores fat. Most people with this condition are obese before one year of age. Other symptoms include constant hunger and abnormal behaviors related to food. People affected with LEPR deficiency have low levels of sex hormones (hypogonadotropic hypogonadism) resulting in late or absent puberty and infertility. LEPR deficiency is caused by changes (mutations or variants) in the LEPR gene, which is responsible for making the receptor that interacts with a protein called leptin. Leptin is important for regulating appetite and growth of body fat. This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Diet, behavior modification, exercise programs and bariatric surgery have been used to help manage the symptoms of LEPR deficiency. Treatment is available for this condition using a drug called setmelanotide. With treatment, people with LEPR deficiency develop a normal appetite, lose weight and fat and can maintain the weight loss.IntroductionLEPR deficiency is rare, making it difficult to predict exactly how it will affect someone who is newly diagnosed with this condition. It is one of several conditions that include early-onset obesity and these conditions can be difficult to distinguish from each other without a careful physical examination and genetic testing.
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LEPR Deficiency
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Symptoms of LEPR Deficiency
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The symptoms of LEPR deficiency are different from person to person, with the most common symptom being early onset obesity. At birth, babies with LEPR deficiency have a normal weight. The earliest symptoms are constant hunger and excessive eating (hyperphagia) leading to rapid weight gain and obesity before one year of age. People with LEPR deficiency always feel hungry even after eating a full meal and often have abnormal behaviors related to food. Many have low levels of sex hormones (hypogonadotropic hypogonadism) causing delayed or absent puberty and infertility. Other symptoms may include low thyroid hormone and insulin resistance, which can lead to type 2 diabetes. Some children with LEPR deficiency get frequent infections because their immune system doesn’t work correctly. Excessive weight gain can lead to other symptoms such as abnormal bone growth, liver disease and difficultly walking.
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Symptoms of LEPR Deficiency. The symptoms of LEPR deficiency are different from person to person, with the most common symptom being early onset obesity. At birth, babies with LEPR deficiency have a normal weight. The earliest symptoms are constant hunger and excessive eating (hyperphagia) leading to rapid weight gain and obesity before one year of age. People with LEPR deficiency always feel hungry even after eating a full meal and often have abnormal behaviors related to food. Many have low levels of sex hormones (hypogonadotropic hypogonadism) causing delayed or absent puberty and infertility. Other symptoms may include low thyroid hormone and insulin resistance, which can lead to type 2 diabetes. Some children with LEPR deficiency get frequent infections because their immune system doesn’t work correctly. Excessive weight gain can lead to other symptoms such as abnormal bone growth, liver disease and difficultly walking.
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LEPR Deficiency
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Causes of LEPR Deficiency
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LEPR deficiency is caused by pathogenic variants (mutations) in the LEPR gene. The LEPR gene is responsible for making the leptin receptor, which works together with the protein, leptin. Leptin is made by fat cells and helps regulate energy storage in the body by balancing how much fat is made and how much is burned for energy. Without leptin receptors, leptin can’t do its job and the body doesn’t recognize when the body has enough energy and it’s time to stop eating.LEPR deficiency is inherited in families in a recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
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Causes of LEPR Deficiency. LEPR deficiency is caused by pathogenic variants (mutations) in the LEPR gene. The LEPR gene is responsible for making the leptin receptor, which works together with the protein, leptin. Leptin is made by fat cells and helps regulate energy storage in the body by balancing how much fat is made and how much is burned for energy. Without leptin receptors, leptin can’t do its job and the body doesn’t recognize when the body has enough energy and it’s time to stop eating.LEPR deficiency is inherited in families in a recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
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LEPR Deficiency
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Affects of LEPR Deficiency
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LEPR deficiency is a very rare disorder. In 2021, approximately 88 patients had been reported worldwide. It has been estimated that 1.34 per 1 million people may have this condition.
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Affects of LEPR Deficiency. LEPR deficiency is a very rare disorder. In 2021, approximately 88 patients had been reported worldwide. It has been estimated that 1.34 per 1 million people may have this condition.
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LEPR Deficiency
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Related disorders of LEPR Deficiency
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LEPR deficiency is one of several rare inherited conditions that include early-onset obesity with few or no other signs or symptoms. These conditions are due to variants in one of the genes that normally work together to help regulate hunger and growth of body fat. These conditions may be difficult to diagnose based solely on clinical examination and sometimes genetic testing is the only way to tell the difference between them.Some of these conditions include:Congenital leptin deficiencyCongenital leptin deficiency (CLD) is a rare, inherited condition that affects how the body processes energy, responds to food and stores fat. Infants with CLD are constantly hungry and quickly gain weight and become obese. Children with CLD have extreme hunger (hyperphagia), low energy and abnormal behaviors related to food. Many people with CLD produce little or no sex hormones (hypogonadotropic hypogonadism) resulting in late or absent puberty and infertility. CLD is caused by variants in the LEP gene, which is responsible for making a protein called leptin. Leptin is important for regulating appetite and growth of body fat. This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Diet, behavior modification, exercise programs and bariatric surgery have been used to help manage the symptoms of CLD. Treatment is available for this condition using a drug called metreleptin, a recombinant form of human leptin, which reverses the symptoms of CLD. With treatment, people with CLD develop a normal appetite, lose weight and fat and regain normal sex hormone levels.PCSK1 deficiencyPCSK1 deficiency is a very rare inherited disorder that affects the metabolism and appetite. Severe diarrhea, digestive problems and slow growth are the earliest symptoms which tend to slightly diminish with time, followed by extreme hunger and obesity in early childhood. Excessive thirst and frequent urination (polyuria polydipsia syndrome) are common. Other symptoms related to abnormalities of the endocrine glands include growth hormone deficiency, low thyroid hormone and adrenal gland disorders. PCSK1 deficiency is caused by variants in the PCSK1 gene and is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms, laboratory testing and the results of genetic testing. Treatment is available for this condition using a drug called setmelanotide. This drug has been approved for treating people age six and over with PCSK1 deficiency and reverses the symptoms including obesity. Less than 50 people have been reported with PCSK1 deficiency.POMC deficiencyPOMC deficiency affects the way the body stores and uses energy. The main symptoms include constant hunger and excessive feeding, known as hyperphagia. Hyperphagia leads to obesity by one year of age, and without treatment, people with POMC deficiency remain obese throughout life. Other symptoms include low levels of a hormone called adrenocorticotropic hormone (ACTH) and adrenal insufficiency, which can be fatal if not treated early. Many individuals with POMC deficiency also have pale skin and hair. POMC deficiency is caused by variants in the POMC gene and is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and genetic testing. Treatment is available for people with POMC deficiency over the age of six using a drug called setmelanotide. This drug reverses the constant hunger and allows people with POMC deficiency to lose weight. This condition is very rare, and it is difficult to predict how this condition will impact someone with a new diagnosis.Obesity due to melanocortin 4 receptor (MC4R) gene variantsThis is the most common cause of early-onset obesity due to a single gene. People with only one MC4R gene variant are affected. Affected people show severe hunger and develop obesity during childhood. Weight and length are normal at birth. People with MC4R deficiency are often taller than average, which is one of the distinguishing features of this condition.People with two MC4R gene variants develop an extreme form of obesity comparable to people with leptin or leptin receptor deficiency. During the first year of life, affected babies develop extreme hunger and rapidly gain weight. Other symptoms include increased insulin in the blood which can lead to type 2 diabetes. For more information see: Welcome to the Melanocortin 4 Receptor website at https://www.mc4r.org.uk/There are other inherited conditions that include obesity in childhood as one of several features. People with these conditions have other signs and symptoms along with excess weight. These conditions include:Bardet-Biedl syndrome (BBS)BBS impacts multiple body systems and is classically defined by six features. People with BBS gain excessive weight, especially around the abdomen. They often also have intellectual disabilities. The kidneys, eyes and function of the genitalia may be compromised. People with BBS may also be born with an extra digit on the hands. The severity and symptoms of BBS vary, even among individuals in the same family. For more information on this disorder, choose “Bardet-Biedl syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/bardet-biedl-syndrome/Alström syndrome Alström syndrome is a rare complex disorder that includes a wide variety of symptoms affecting multiple organ systems of the body. The disorder is characterized by vision and hearing abnormalities, obesity in childhood, insulin resistance and diabetes mellitus. Other symptoms include heart disease (dilated cardiomyopathy) and slowly progressive kidney dysfunction, potentially leading to kidney failure. Additional symptoms include lung, liver, kidney and endocrine dysfunction. Although some children may experience delays in reaching developmental milestones, intelligence is usually unaffected. Alström syndrome is caused by variants in the ALMS1 gene. The protein made by this gene is involved in ciliary function, cell cycle control and intracellular transport. Alström syndrome is inherited in an autosomal recessive pattern. For more information on this disorder, choose “Alstrom syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/alstrom-syndrome/Prader-Willi syndromePrader-Willi syndrome (PWS) is a multisystem disorder characterized during infancy by lethargy, diminished muscle tone (hypotonia), a weak suck and feeding difficulties with poor weight gain and growth and other hormone deficiencies. In childhood, features of this disorder include short stature, small genitals and an excessive appetite. People with PWS do not feel satisfied after completing a meal (satiety). Without intervention, overeating can lead to life-threatening obesity. The food compulsion requires constant supervision. Individuals with severe obesity may have an increased risk of cardiac insufficiency, sleep apnea, diabetes, respiratory problems and other serious conditions that can cause life-threatening complications. All individuals with PWS have some cognitive impairment that ranges from low normal intelligence with learning disabilities to mild to moderate intellectual disability. Behavioral problems are common and can include temper tantrums, obsessive/compulsive behavior and skin picking. Motor milestones and language development are often delayed. PWS occurs due to changes of specific genes on part of the chromosome 15 inherited from the father. This condition is referred to as a genomic imprinting disorder which depends on which parent passes on the chromosome with the genetic changes to the child. For more information on this disorder, choose “Prader-Willi syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/prader-willi-syndrome/Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome (BWS) is characterized by symptoms and physical findings that vary in range and severity from person to person. Associated features include above-average birth weight, increased growth after birth (macrosomia), a large tongue (macroglossia), enlargement of certain internal organs (organomegaly) and abdominal wall defects (omphalocele, umbilical hernia or diastasis recti). BWS may also be associated with low blood sugar levels, distinctive grooves in the ear lobes (ear creases and ear pits), facial abnormalities and abnormal enlargement of one side or structure of the body (lateralized overgrowth). People with BWS also have an increased risk of developing certain childhood cancers, most commonly Wilms tumor (kidney tumor) and hepatoblastoma (liver tumor). Beckwith-Wiedemann syndrome has been recently reclassified as Beckwith-Wiedemann spectrum as the clinical presentation can vary from patient to patient. Approximately 80% of BWS occurs due to genetic changes that occur randomly. Inherited forms occur in about 5-10% of people with BWS. About 14% of people with BWS have an unknown cause. BWS affects at least one in 10,340 live births. Researchers have determined that BWS results from various abnormalities affecting the normal expression of certain genes that control growth on one part of chromosome 11 (BWS critical region). For more information on this disorder, choose “Beckwith-Wiedemann syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/beckwith-wiedemann-syndrome/
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Related disorders of LEPR Deficiency. LEPR deficiency is one of several rare inherited conditions that include early-onset obesity with few or no other signs or symptoms. These conditions are due to variants in one of the genes that normally work together to help regulate hunger and growth of body fat. These conditions may be difficult to diagnose based solely on clinical examination and sometimes genetic testing is the only way to tell the difference between them.Some of these conditions include:Congenital leptin deficiencyCongenital leptin deficiency (CLD) is a rare, inherited condition that affects how the body processes energy, responds to food and stores fat. Infants with CLD are constantly hungry and quickly gain weight and become obese. Children with CLD have extreme hunger (hyperphagia), low energy and abnormal behaviors related to food. Many people with CLD produce little or no sex hormones (hypogonadotropic hypogonadism) resulting in late or absent puberty and infertility. CLD is caused by variants in the LEP gene, which is responsible for making a protein called leptin. Leptin is important for regulating appetite and growth of body fat. This condition is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and the results of genetic testing. Diet, behavior modification, exercise programs and bariatric surgery have been used to help manage the symptoms of CLD. Treatment is available for this condition using a drug called metreleptin, a recombinant form of human leptin, which reverses the symptoms of CLD. With treatment, people with CLD develop a normal appetite, lose weight and fat and regain normal sex hormone levels.PCSK1 deficiencyPCSK1 deficiency is a very rare inherited disorder that affects the metabolism and appetite. Severe diarrhea, digestive problems and slow growth are the earliest symptoms which tend to slightly diminish with time, followed by extreme hunger and obesity in early childhood. Excessive thirst and frequent urination (polyuria polydipsia syndrome) are common. Other symptoms related to abnormalities of the endocrine glands include growth hormone deficiency, low thyroid hormone and adrenal gland disorders. PCSK1 deficiency is caused by variants in the PCSK1 gene and is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms, laboratory testing and the results of genetic testing. Treatment is available for this condition using a drug called setmelanotide. This drug has been approved for treating people age six and over with PCSK1 deficiency and reverses the symptoms including obesity. Less than 50 people have been reported with PCSK1 deficiency.POMC deficiencyPOMC deficiency affects the way the body stores and uses energy. The main symptoms include constant hunger and excessive feeding, known as hyperphagia. Hyperphagia leads to obesity by one year of age, and without treatment, people with POMC deficiency remain obese throughout life. Other symptoms include low levels of a hormone called adrenocorticotropic hormone (ACTH) and adrenal insufficiency, which can be fatal if not treated early. Many individuals with POMC deficiency also have pale skin and hair. POMC deficiency is caused by variants in the POMC gene and is inherited in an autosomal recessive pattern. Diagnosis is based on a clinical examination, symptoms and genetic testing. Treatment is available for people with POMC deficiency over the age of six using a drug called setmelanotide. This drug reverses the constant hunger and allows people with POMC deficiency to lose weight. This condition is very rare, and it is difficult to predict how this condition will impact someone with a new diagnosis.Obesity due to melanocortin 4 receptor (MC4R) gene variantsThis is the most common cause of early-onset obesity due to a single gene. People with only one MC4R gene variant are affected. Affected people show severe hunger and develop obesity during childhood. Weight and length are normal at birth. People with MC4R deficiency are often taller than average, which is one of the distinguishing features of this condition.People with two MC4R gene variants develop an extreme form of obesity comparable to people with leptin or leptin receptor deficiency. During the first year of life, affected babies develop extreme hunger and rapidly gain weight. Other symptoms include increased insulin in the blood which can lead to type 2 diabetes. For more information see: Welcome to the Melanocortin 4 Receptor website at https://www.mc4r.org.uk/There are other inherited conditions that include obesity in childhood as one of several features. People with these conditions have other signs and symptoms along with excess weight. These conditions include:Bardet-Biedl syndrome (BBS)BBS impacts multiple body systems and is classically defined by six features. People with BBS gain excessive weight, especially around the abdomen. They often also have intellectual disabilities. The kidneys, eyes and function of the genitalia may be compromised. People with BBS may also be born with an extra digit on the hands. The severity and symptoms of BBS vary, even among individuals in the same family. For more information on this disorder, choose “Bardet-Biedl syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/bardet-biedl-syndrome/Alström syndrome Alström syndrome is a rare complex disorder that includes a wide variety of symptoms affecting multiple organ systems of the body. The disorder is characterized by vision and hearing abnormalities, obesity in childhood, insulin resistance and diabetes mellitus. Other symptoms include heart disease (dilated cardiomyopathy) and slowly progressive kidney dysfunction, potentially leading to kidney failure. Additional symptoms include lung, liver, kidney and endocrine dysfunction. Although some children may experience delays in reaching developmental milestones, intelligence is usually unaffected. Alström syndrome is caused by variants in the ALMS1 gene. The protein made by this gene is involved in ciliary function, cell cycle control and intracellular transport. Alström syndrome is inherited in an autosomal recessive pattern. For more information on this disorder, choose “Alstrom syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/alstrom-syndrome/Prader-Willi syndromePrader-Willi syndrome (PWS) is a multisystem disorder characterized during infancy by lethargy, diminished muscle tone (hypotonia), a weak suck and feeding difficulties with poor weight gain and growth and other hormone deficiencies. In childhood, features of this disorder include short stature, small genitals and an excessive appetite. People with PWS do not feel satisfied after completing a meal (satiety). Without intervention, overeating can lead to life-threatening obesity. The food compulsion requires constant supervision. Individuals with severe obesity may have an increased risk of cardiac insufficiency, sleep apnea, diabetes, respiratory problems and other serious conditions that can cause life-threatening complications. All individuals with PWS have some cognitive impairment that ranges from low normal intelligence with learning disabilities to mild to moderate intellectual disability. Behavioral problems are common and can include temper tantrums, obsessive/compulsive behavior and skin picking. Motor milestones and language development are often delayed. PWS occurs due to changes of specific genes on part of the chromosome 15 inherited from the father. This condition is referred to as a genomic imprinting disorder which depends on which parent passes on the chromosome with the genetic changes to the child. For more information on this disorder, choose “Prader-Willi syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/prader-willi-syndrome/Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome (BWS) is characterized by symptoms and physical findings that vary in range and severity from person to person. Associated features include above-average birth weight, increased growth after birth (macrosomia), a large tongue (macroglossia), enlargement of certain internal organs (organomegaly) and abdominal wall defects (omphalocele, umbilical hernia or diastasis recti). BWS may also be associated with low blood sugar levels, distinctive grooves in the ear lobes (ear creases and ear pits), facial abnormalities and abnormal enlargement of one side or structure of the body (lateralized overgrowth). People with BWS also have an increased risk of developing certain childhood cancers, most commonly Wilms tumor (kidney tumor) and hepatoblastoma (liver tumor). Beckwith-Wiedemann syndrome has been recently reclassified as Beckwith-Wiedemann spectrum as the clinical presentation can vary from patient to patient. Approximately 80% of BWS occurs due to genetic changes that occur randomly. Inherited forms occur in about 5-10% of people with BWS. About 14% of people with BWS have an unknown cause. BWS affects at least one in 10,340 live births. Researchers have determined that BWS results from various abnormalities affecting the normal expression of certain genes that control growth on one part of chromosome 11 (BWS critical region). For more information on this disorder, choose “Beckwith-Wiedemann syndrome” as your search term in the Rare Disease Database. https://rarediseases.org/rare-diseases/beckwith-wiedemann-syndrome/
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LEPR Deficiency
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Diagnosis of LEPR Deficiency
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LEPR deficiency is diagnosed based on a clinical examination, symptoms and the results of laboratory and genetic testing. Because there are several inherited conditions that include excessive hunger and early-onset obesity, genetic testing may be done to help make a specific diagnosis. This testing often involves using a gene panel, allowing the lab to look for genetic variants in several different genes at the same time. Genetic testing is usually done with a blood or saliva sample. It is helpful to speak to a genetics professional before having genetic testing to learn more about the risk, benefits and limitations.
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Diagnosis of LEPR Deficiency. LEPR deficiency is diagnosed based on a clinical examination, symptoms and the results of laboratory and genetic testing. Because there are several inherited conditions that include excessive hunger and early-onset obesity, genetic testing may be done to help make a specific diagnosis. This testing often involves using a gene panel, allowing the lab to look for genetic variants in several different genes at the same time. Genetic testing is usually done with a blood or saliva sample. It is helpful to speak to a genetics professional before having genetic testing to learn more about the risk, benefits and limitations.
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LEPR Deficiency
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Therapies of LEPR Deficiency
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Setmelanotide has been approved by the U.S. Food and Drug Administration (FDA) for people six years and older with obesity due to LEPR deficiency which has been diagnosed by genetic testing. This drug is given by daily injection. People taking setmelanotide are able to control their appetite, lose weight and maintain weight loss. People with LEPR deficiency may be treated by a variety of different medical specialists, including gastroenterologists, nutritionists and endocrinologists. A psychologist or other mental health professional can help people cope with the symptoms of this condition.
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Therapies of LEPR Deficiency. Setmelanotide has been approved by the U.S. Food and Drug Administration (FDA) for people six years and older with obesity due to LEPR deficiency which has been diagnosed by genetic testing. This drug is given by daily injection. People taking setmelanotide are able to control their appetite, lose weight and maintain weight loss. People with LEPR deficiency may be treated by a variety of different medical specialists, including gastroenterologists, nutritionists and endocrinologists. A psychologist or other mental health professional can help people cope with the symptoms of this condition.
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LEPR Deficiency
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nord_711_0
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Overview of Leprechaunism
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Leprechaunism is an extremely rare disorder characterized by abnormal resistance to insulin that results in a variety of distinguishing characteristics, including growth delays and abnormalities affecting the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Affected infants may also have distinctive characteristics of the head and face (craniofacial region), low birth weight, skin abnormalities, and enlargement of the breast and clitoris in females and the penis in males. Leprechaunism is inherited in an autosomal recessive pattern.
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Overview of Leprechaunism. Leprechaunism is an extremely rare disorder characterized by abnormal resistance to insulin that results in a variety of distinguishing characteristics, including growth delays and abnormalities affecting the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Affected infants may also have distinctive characteristics of the head and face (craniofacial region), low birth weight, skin abnormalities, and enlargement of the breast and clitoris in females and the penis in males. Leprechaunism is inherited in an autosomal recessive pattern.
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Leprechaunism
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Symptoms of Leprechaunism
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Leprechaunism is characterized by growth delays, as well as abnormalities of the head and face (craniofacial region) and of the endocrine system. Many of the symptoms associated with leprechaunism are present at birth (congenital). The range and severity of symptoms and physical characteristics may vary from person to person.Most infants with leprechaunism exhibit delayed growth before and after birth (pre- and postnatal growth deficiency), delayed bone age or maturation. Affected infants tend to have a low birth weight, may fail to gain weight or grow at the expected rate (failure to thrive), and may become abnormally thin (emaciated). They often lack muscle mass.Infants with leprechaunism have distinctive facial features, including abnormally large, low-set and poorly developed ears; an unusually flat bridge of the nose; large, thick lips; an abnormally large mouth (macrostomia); and widely spaced eyes (hyptertelorism). Affected infants may also have an abnormally small head (microcephaly).Leprechaunism is associated with abnormal darkening and thickening of patches of skin in certain areas of the body (acanthosis nigricans), unusual thickening of the skin (pachyderma), excessive hair growth (hirsutism), and malformation (dysplasia) of the nails. In addition, infants with leprechaunism exhibit absence of most of the body fat under the skin (subcutaneous adipose tissue).Leprechaunism is also characterized by abnormalities of the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Such abnormalities include excessive secretion of the hormone insulin (hyperinsulinemia). Insulin regulates blood sugar (glucose) levels by promoting the movement of glucose into bodily cells. Infants with leprechaunism fail to use insulin effectively (insulin resistant). Because of this, they may experience abnormally high blood sugar levels (hyperglycemia) after eating a meal (postprandial) and abnormally low blood sugar levels (hypoglycemia) when not eating.Additional abnormalities resulting from improper function of the endocrine system include abnormal enlargement of the breast and clitoris in females and the penis in males. In some cases, cysts have formed in the ovaries. Hypertrophic cadiomyopathy may be seen in these patients as in diabetic mother babies.Infants with leprechaunism may have additional abnormalities, including intellectual disability, abnormally large hands and feet, an unusually widened (dilated) or enlarged (distended) stomach, abnormal amounts of iron in the liver, and/or stoppage of the flow of bile (cholestasis) from the liver. In addition, affected infants may experience protrusion of portions of the large intestine through an abnormal opening in musculature lining the abdominal cavity in the area of the groin (inguinal hernia) or protrusion of part of the intestine through the abdominal wall near the navel (umbilical hernia). Affected infants are also more susceptible to repeated infections.
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Symptoms of Leprechaunism. Leprechaunism is characterized by growth delays, as well as abnormalities of the head and face (craniofacial region) and of the endocrine system. Many of the symptoms associated with leprechaunism are present at birth (congenital). The range and severity of symptoms and physical characteristics may vary from person to person.Most infants with leprechaunism exhibit delayed growth before and after birth (pre- and postnatal growth deficiency), delayed bone age or maturation. Affected infants tend to have a low birth weight, may fail to gain weight or grow at the expected rate (failure to thrive), and may become abnormally thin (emaciated). They often lack muscle mass.Infants with leprechaunism have distinctive facial features, including abnormally large, low-set and poorly developed ears; an unusually flat bridge of the nose; large, thick lips; an abnormally large mouth (macrostomia); and widely spaced eyes (hyptertelorism). Affected infants may also have an abnormally small head (microcephaly).Leprechaunism is associated with abnormal darkening and thickening of patches of skin in certain areas of the body (acanthosis nigricans), unusual thickening of the skin (pachyderma), excessive hair growth (hirsutism), and malformation (dysplasia) of the nails. In addition, infants with leprechaunism exhibit absence of most of the body fat under the skin (subcutaneous adipose tissue).Leprechaunism is also characterized by abnormalities of the endocrine system (i.e., the system of glands that secrete hormones into the blood system). Such abnormalities include excessive secretion of the hormone insulin (hyperinsulinemia). Insulin regulates blood sugar (glucose) levels by promoting the movement of glucose into bodily cells. Infants with leprechaunism fail to use insulin effectively (insulin resistant). Because of this, they may experience abnormally high blood sugar levels (hyperglycemia) after eating a meal (postprandial) and abnormally low blood sugar levels (hypoglycemia) when not eating.Additional abnormalities resulting from improper function of the endocrine system include abnormal enlargement of the breast and clitoris in females and the penis in males. In some cases, cysts have formed in the ovaries. Hypertrophic cadiomyopathy may be seen in these patients as in diabetic mother babies.Infants with leprechaunism may have additional abnormalities, including intellectual disability, abnormally large hands and feet, an unusually widened (dilated) or enlarged (distended) stomach, abnormal amounts of iron in the liver, and/or stoppage of the flow of bile (cholestasis) from the liver. In addition, affected infants may experience protrusion of portions of the large intestine through an abnormal opening in musculature lining the abdominal cavity in the area of the groin (inguinal hernia) or protrusion of part of the intestine through the abdominal wall near the navel (umbilical hernia). Affected infants are also more susceptible to repeated infections.
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Causes of Leprechaunism
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Leprechaunism may be caused by disruption or changes (mutations) of the insulin receptor gene. Due to the mutation in the insulin receptor gene, individuals with leprechaunism are unable to use insulin effectively. Insulin is a hormone produced by the pancreas that plays an important role in the absorption of sugar (glucose) into muscle cells. Glucose is the body’s main source of energy. Some symptoms associated with leprechaunism, including growth deficiencies and hyperglycemia, develop as a result of severe insulin resistance of affected individuals.Leprechaunism 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.
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Causes of Leprechaunism. Leprechaunism may be caused by disruption or changes (mutations) of the insulin receptor gene. Due to the mutation in the insulin receptor gene, individuals with leprechaunism are unable to use insulin effectively. Insulin is a hormone produced by the pancreas that plays an important role in the absorption of sugar (glucose) into muscle cells. Glucose is the body’s main source of energy. Some symptoms associated with leprechaunism, including growth deficiencies and hyperglycemia, develop as a result of severe insulin resistance of affected individuals.Leprechaunism 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.
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Affects of Leprechaunism
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In reported cases, leprechaunism has occurred twice as often in females as in males More than 50 cases have been reported in the medical literature. Leprechaunism was first identified in the 1948 by Dr. W.L. Donohue.
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Affects of Leprechaunism. In reported cases, leprechaunism has occurred twice as often in females as in males More than 50 cases have been reported in the medical literature. Leprechaunism was first identified in the 1948 by Dr. W.L. Donohue.
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Related disorders of Leprechaunism
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Symptoms of the following disorders can be similar to those of leprechaunism. Comparisons may be useful for a differential diagnosis:Patterson pseudoleprechaunism syndrome is an extremely rare genetic disorder characterized by a normal birth weight, bronze discoloration of the skin (hyperpigmentation), loose skin on the hands and feet (cutis gyrata), and malformation (dysplasia) of the skeleton. Abnormalities affecting the endocrine system include enlargement of the adrenal glands and the adrenal cortex (hyperadrenocorticism) and diabetes mellitus. The exact cause of Patterson pseudoleprechaunism syndrome is not known.Williams syndrome is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, varying levels of mental deficiency, and distinctive facial abnormalities that typically become more pronounced with age. Characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also be present including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Williams syndrome is associated with peripheral pulmonary stenosis and supravalvular aortic stenosis. Stenosis in arterial system may be seen on renal arteries, too. Williams syndrome may also be associated with heart (cardiac) defects, abnormally musculoskeletal defects, and/or other abnormalities. In addition, most affected individuals have mild to moderate intellectual disability; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; and a short attention span with easy distractibility. In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). (For more information on this disorder, choose “Williams syndrome” as your search term in the Rare Disease Database.)
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Related disorders of Leprechaunism. Symptoms of the following disorders can be similar to those of leprechaunism. Comparisons may be useful for a differential diagnosis:Patterson pseudoleprechaunism syndrome is an extremely rare genetic disorder characterized by a normal birth weight, bronze discoloration of the skin (hyperpigmentation), loose skin on the hands and feet (cutis gyrata), and malformation (dysplasia) of the skeleton. Abnormalities affecting the endocrine system include enlargement of the adrenal glands and the adrenal cortex (hyperadrenocorticism) and diabetes mellitus. The exact cause of Patterson pseudoleprechaunism syndrome is not known.Williams syndrome is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, varying levels of mental deficiency, and distinctive facial abnormalities that typically become more pronounced with age. Characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also be present including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Williams syndrome is associated with peripheral pulmonary stenosis and supravalvular aortic stenosis. Stenosis in arterial system may be seen on renal arteries, too. Williams syndrome may also be associated with heart (cardiac) defects, abnormally musculoskeletal defects, and/or other abnormalities. In addition, most affected individuals have mild to moderate intellectual disability; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; and a short attention span with easy distractibility. In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). (For more information on this disorder, choose “Williams syndrome” as your search term in the Rare Disease Database.)
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Diagnosis of Leprechaunism
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The diagnosis of leprechaunism may be confirmed by a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and physical findings. The diagnosis requires measurement of insulin levels, with a blood test, and confirmation of defective insulin binding on the cells known as fibroblasts.Prenatal diagnosis is possible through analysis of DNA obtain through a procedure known as amniocentesis. During amniocentesis, a sample of fluid that surrounds the developing fetus (amniotic fluid) is removed and studied. DNA obtained from amniotic cells is analyzed through a test known as polymerase chain reaction (PCR). PCR, a laboratory technique that many have described as a form of “photocopying,” enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In leprechaunism, polymerase chain reaction is used to identify mutations to the insulin receptor gene.
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Diagnosis of Leprechaunism. The diagnosis of leprechaunism may be confirmed by a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and physical findings. The diagnosis requires measurement of insulin levels, with a blood test, and confirmation of defective insulin binding on the cells known as fibroblasts.Prenatal diagnosis is possible through analysis of DNA obtain through a procedure known as amniocentesis. During amniocentesis, a sample of fluid that surrounds the developing fetus (amniotic fluid) is removed and studied. DNA obtained from amniotic cells is analyzed through a test known as polymerase chain reaction (PCR). PCR, a laboratory technique that many have described as a form of “photocopying,” enables researchers to enlarge and repeatedly copy sequences of DNA. As a result, they are able to closely analyze DNA and more easily identify genes and genetic changes (mutations). In leprechaunism, polymerase chain reaction is used to identify mutations to the insulin receptor gene.
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Therapies of Leprechaunism
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Treatment
The treatment of leprechaunism 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 assess and treat endocrine abnormalities (endocrinologists), and specialists who assess and treat skin abnormalities (dermatologists) and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
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Therapies of Leprechaunism. Treatment
The treatment of leprechaunism 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 assess and treat endocrine abnormalities (endocrinologists), and specialists who assess and treat skin abnormalities (dermatologists) and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.
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Overview of Leprosy
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Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium leprae. For many years, it was considered a mysterious disorder associated with some type of curse, and persons with the disease were isolated and ostracized. Today, there is effective treatment and the disease can be cured. There is no longer any justification for isolating persons with leprosy.The disease can affect the skin, mucous membranes, and eyes and some of the nerves that are located outside the central nervous system (peripheral nerves). These are primarily the nerves of the hands, feet, and eyes, and some of the nerves in the skin. In severe, untreated cases, loss of sensation, muscle paralysis of hands and feet, disfigurement, and blindness may occur.Leprosy has traditionally been classified into two major types, tuberculoid and lepromatous. Patients with tuberculoid leprosy have limited disease and relatively few bacteria in the skin and nerves, while lepromatous patients have widespread disease and large numbers of bacteria. Tuberculoid leprosy is characterized by a few flat or slightly raised skin lesions of various sizes that are typically pale or slightly red, dry, hairless, and numb to touch (anesthetic). Lepromatous leprosy is at the other end of the spectrum, with a much more generalized disease, diffuse involvement of the skin, thickening of many peripheral nerves, and at times involvement of other organs, such as eyes, nose, testicles, and bone. There are also intermediate subtypes between these two extremes that are commonly known as borderline leprosy. The intermediate subtypes are borderline tuberculoid, midborderline, and borderline lepromatous leprosy. Borderline leprosy and the subtypes are characterized by more extensive disease than polar tuberculoid, with more numerous skin lesions and more nerve involvement, but not as widespread disease as in lepromatous leprosy. Indeterminate leprosy refers to a very early form of leprosy that consists of a single skin lesion with slightly diminished sensation to touch. It will usually progress to one of the major types of leprosy.In 1982, the World Health Organization proposed a simplified classification that has only two classifications, Paucibacillary (PB) and Multibacillary (MB), leprosy. This classification is now used worldwide for treatment purposes. The older and somewhat more complex classification is still used in some programs, especially for clinical research studies. The Paucibacillary classification encompasses indeterminate, tuberculoid and borderline tuberculoid leprosy. The Multibacillary classification includes midborderline, borderline lepromatous and lepromatous leprosy.
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Overview of Leprosy. Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium leprae. For many years, it was considered a mysterious disorder associated with some type of curse, and persons with the disease were isolated and ostracized. Today, there is effective treatment and the disease can be cured. There is no longer any justification for isolating persons with leprosy.The disease can affect the skin, mucous membranes, and eyes and some of the nerves that are located outside the central nervous system (peripheral nerves). These are primarily the nerves of the hands, feet, and eyes, and some of the nerves in the skin. In severe, untreated cases, loss of sensation, muscle paralysis of hands and feet, disfigurement, and blindness may occur.Leprosy has traditionally been classified into two major types, tuberculoid and lepromatous. Patients with tuberculoid leprosy have limited disease and relatively few bacteria in the skin and nerves, while lepromatous patients have widespread disease and large numbers of bacteria. Tuberculoid leprosy is characterized by a few flat or slightly raised skin lesions of various sizes that are typically pale or slightly red, dry, hairless, and numb to touch (anesthetic). Lepromatous leprosy is at the other end of the spectrum, with a much more generalized disease, diffuse involvement of the skin, thickening of many peripheral nerves, and at times involvement of other organs, such as eyes, nose, testicles, and bone. There are also intermediate subtypes between these two extremes that are commonly known as borderline leprosy. The intermediate subtypes are borderline tuberculoid, midborderline, and borderline lepromatous leprosy. Borderline leprosy and the subtypes are characterized by more extensive disease than polar tuberculoid, with more numerous skin lesions and more nerve involvement, but not as widespread disease as in lepromatous leprosy. Indeterminate leprosy refers to a very early form of leprosy that consists of a single skin lesion with slightly diminished sensation to touch. It will usually progress to one of the major types of leprosy.In 1982, the World Health Organization proposed a simplified classification that has only two classifications, Paucibacillary (PB) and Multibacillary (MB), leprosy. This classification is now used worldwide for treatment purposes. The older and somewhat more complex classification is still used in some programs, especially for clinical research studies. The Paucibacillary classification encompasses indeterminate, tuberculoid and borderline tuberculoid leprosy. The Multibacillary classification includes midborderline, borderline lepromatous and lepromatous leprosy.
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Symptoms of Leprosy
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The earliest symptoms are usually skin lesions that are typically flat, pale (hypopigmented) or reddish (erythematous) spots in the skin with slightly decreased sensitivity to touch or pain. These lesions typically do not present with other symptoms, such as burning or pain. There may be some hair loss in the affected area. As the skin lesions progress, they may become raised and, in some cases, nodules may form. The symptoms of nerve involvement include diminished sensation or feeling in the affected areas (anesthesia) and, sometimes, burning and tingling sensations (paresthesias). In more advanced cases, there may be weakness, paralysis, and atrophy of muscle in the hands or feet.Persons with tuberculoid and borderline tuberculoid leprosy have limited disease with relatively few skin lesions and only a few affected nerves. However, early in the course of the disease, they may have significant sensory loss and muscle weakness, even though only one hand or foot is involved. Persons with lepromatous leprosy may have minimal loss of sensation at the onset; however, if untreated, they will develop extensive involvement of the skin and nerves. The complications that may occur include eye involvement and deformities of the face, hands, and feet. Deformities of the face can result from destruction of the partition in the nose that divides the nostrils (nasal septum) and other facial tissues. In advanced disease, persons with lepromatous leprosy may lose their eyebrows and eyelashes, and the eyelids may become paralyzed so that individuals cannot blink or close their eyes properly. The earlobes may enlarge or become wrinkled. Deformities of the hands and feet may result from muscle paralysis and repeated trauma that is not felt due to sensory loss.The most serious complication of leprosy is the nerve damage that may occur sometimes even after treatment is begun. Much of the nerve damage occurs during a type of immunologic problem that occurs in 25 to 50% of patients during treatment and is commonly known as a reaction. Reactions are not drug reactions or allergies, but are the patient's own immune system reacting against the dead bacteria that are still in the skin and nerves. Patients with the intermediate or borderline type of disease may get a type of reaction known as reversal reaction, in which there is redness and swelling of the skin lesions and swelling, tenderness, and pain in the nerves of the hands and feet. During this process, nerve damage can occur.The second type of reaction occurs only in borderline lepromatous and lepromatous disease, and is known as erythema nodosum leprosum (ENL). This syndrome is characterized by fever and raised, red, painful skin nodules. There may also be pain and tenderness of the nerves with subsequent nerve damage in the hands and feet. ENL may also be associated with joint disease (polyarthralgia), eye inflammation, and inflammation of the testicles.During reactions and at times without any signs of reaction, there may be damage to the nerves of the face resulting in weakness of closure of the eyelids and loss of feeling in the cornea (corneal anesthesia). This can result in corneal dryness and scarring and lead to blindness. Persons with lepromatous leprosy may also have inflammation of the iris and the sclera of the eye, which can lead to visual impairment and, in some cases, blindness.
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Symptoms of Leprosy. The earliest symptoms are usually skin lesions that are typically flat, pale (hypopigmented) or reddish (erythematous) spots in the skin with slightly decreased sensitivity to touch or pain. These lesions typically do not present with other symptoms, such as burning or pain. There may be some hair loss in the affected area. As the skin lesions progress, they may become raised and, in some cases, nodules may form. The symptoms of nerve involvement include diminished sensation or feeling in the affected areas (anesthesia) and, sometimes, burning and tingling sensations (paresthesias). In more advanced cases, there may be weakness, paralysis, and atrophy of muscle in the hands or feet.Persons with tuberculoid and borderline tuberculoid leprosy have limited disease with relatively few skin lesions and only a few affected nerves. However, early in the course of the disease, they may have significant sensory loss and muscle weakness, even though only one hand or foot is involved. Persons with lepromatous leprosy may have minimal loss of sensation at the onset; however, if untreated, they will develop extensive involvement of the skin and nerves. The complications that may occur include eye involvement and deformities of the face, hands, and feet. Deformities of the face can result from destruction of the partition in the nose that divides the nostrils (nasal septum) and other facial tissues. In advanced disease, persons with lepromatous leprosy may lose their eyebrows and eyelashes, and the eyelids may become paralyzed so that individuals cannot blink or close their eyes properly. The earlobes may enlarge or become wrinkled. Deformities of the hands and feet may result from muscle paralysis and repeated trauma that is not felt due to sensory loss.The most serious complication of leprosy is the nerve damage that may occur sometimes even after treatment is begun. Much of the nerve damage occurs during a type of immunologic problem that occurs in 25 to 50% of patients during treatment and is commonly known as a reaction. Reactions are not drug reactions or allergies, but are the patient's own immune system reacting against the dead bacteria that are still in the skin and nerves. Patients with the intermediate or borderline type of disease may get a type of reaction known as reversal reaction, in which there is redness and swelling of the skin lesions and swelling, tenderness, and pain in the nerves of the hands and feet. During this process, nerve damage can occur.The second type of reaction occurs only in borderline lepromatous and lepromatous disease, and is known as erythema nodosum leprosum (ENL). This syndrome is characterized by fever and raised, red, painful skin nodules. There may also be pain and tenderness of the nerves with subsequent nerve damage in the hands and feet. ENL may also be associated with joint disease (polyarthralgia), eye inflammation, and inflammation of the testicles.During reactions and at times without any signs of reaction, there may be damage to the nerves of the face resulting in weakness of closure of the eyelids and loss of feeling in the cornea (corneal anesthesia). This can result in corneal dryness and scarring and lead to blindness. Persons with lepromatous leprosy may also have inflammation of the iris and the sclera of the eye, which can lead to visual impairment and, in some cases, blindness.
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Causes of Leprosy
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Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium leprae. The disease has been known and described for several thousand years in India and China. Over 100 years ago, Armauer Hansen in Norway identified the bacteria as the cause of leprosy.The way in which the disease is transmitted is not fully understood. The bacteria grow only in living hosts and have not been grown in laboratory media, except in certain kinds of mice, rats, and armadillos. Some wild armadillos also carry the bacteria. The most likely way of spread appears to be through the respiratory tract, since large numbers of bacteria are sometimes found in the noses and mouths of untreated patients. When these are released into the environment, they can be inhaled by other susceptible persons.Most people have a natural immunity to the disease and will not contract it even if they are exposed to it. Only about 5 percent of all people are susceptible to the disease. More than one-half of new cases give no history of any known contact with a leprosy patient.
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Causes of Leprosy. Leprosy is a chronic infectious disease of humans caused by the bacteria Mycobacterium leprae. The disease has been known and described for several thousand years in India and China. Over 100 years ago, Armauer Hansen in Norway identified the bacteria as the cause of leprosy.The way in which the disease is transmitted is not fully understood. The bacteria grow only in living hosts and have not been grown in laboratory media, except in certain kinds of mice, rats, and armadillos. Some wild armadillos also carry the bacteria. The most likely way of spread appears to be through the respiratory tract, since large numbers of bacteria are sometimes found in the noses and mouths of untreated patients. When these are released into the environment, they can be inhaled by other susceptible persons.Most people have a natural immunity to the disease and will not contract it even if they are exposed to it. Only about 5 percent of all people are susceptible to the disease. More than one-half of new cases give no history of any known contact with a leprosy patient.
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Affects of Leprosy
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Leprosy is relatively rare in the United States but is prevalent in some countries of Asia, Africa, and South America. There are about 7,000 persons in the United States that have been treated for the disease, and from 150-200 new cases are reported annually in the United States. About 85% of the U.S. cases are persons who have immigrated from other countries. North American Indians in the U.S.A. appear to be immune to this disease.Worldwide, there are about 700,000 new cases reported each year, with about 800,000 cases under treatment in 1998. There are an additional estimated two to three million persons who have residual deformities and disabilities from the disease, even though they have been cured of the infection. Some of the countries with the largest number of cases are India, Brazil, Indonesia, Bangladesh, Myanmar, Nigeria, and Mozambique.
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Affects of Leprosy. Leprosy is relatively rare in the United States but is prevalent in some countries of Asia, Africa, and South America. There are about 7,000 persons in the United States that have been treated for the disease, and from 150-200 new cases are reported annually in the United States. About 85% of the U.S. cases are persons who have immigrated from other countries. North American Indians in the U.S.A. appear to be immune to this disease.Worldwide, there are about 700,000 new cases reported each year, with about 800,000 cases under treatment in 1998. There are an additional estimated two to three million persons who have residual deformities and disabilities from the disease, even though they have been cured of the infection. Some of the countries with the largest number of cases are India, Brazil, Indonesia, Bangladesh, Myanmar, Nigeria, and Mozambique.
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Related disorders of Leprosy
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There are no closely related diseases.
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Related disorders of Leprosy. There are no closely related diseases.
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Diagnosis of Leprosy
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The diagnosis can usually be made by the history and characteristic findings on examination. The important findings are decreased ability to feel light touch in a skin spot, enlarged or tender nerves in the arms or legs, numbness in a hand or foot, and finding the bacteria in the skin. There may also be loss of hair in the affected skin areas. A special type of skin smear is commonly done and will demonstrate the bacteria in the skin in lepromatous and borderline lepromatous cases. The bacteria are too few in tuberculoid cases to be found in a skin smear. A skin biopsy of a lesion can also be helpful to confirm the diagnosis. There are no blood tests or skin tests at the present time that are helpful in the diagnosis.
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Diagnosis of Leprosy. The diagnosis can usually be made by the history and characteristic findings on examination. The important findings are decreased ability to feel light touch in a skin spot, enlarged or tender nerves in the arms or legs, numbness in a hand or foot, and finding the bacteria in the skin. There may also be loss of hair in the affected skin areas. A special type of skin smear is commonly done and will demonstrate the bacteria in the skin in lepromatous and borderline lepromatous cases. The bacteria are too few in tuberculoid cases to be found in a skin smear. A skin biopsy of a lesion can also be helpful to confirm the diagnosis. There are no blood tests or skin tests at the present time that are helpful in the diagnosis.
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Therapies of Leprosy
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TreatmentLeprosy is a treatable and curable disease. The vast majority of patients can take their medication at home and continue their regular work and other activities. Patients with leprosy do not need to be isolated. It is important to note that the drugs used to treat leprosy are very effective in killing the bacteria, and patients on treatment are not infectious and do not spread the disease.The currently available drugs are very effective, and treatment is much shorter than was common 20 years ago. The major drugs are dapsone, rifampin, and clofazimine. Dapsone and rifampin can be given for six months for patients with PB disease (indeterminate, tuberculoid or borderline tuberculoid disease), and dapsone, rifampin, and clofazimine are given for two years for patients with MB disease (midborderline, borderline lepromatous and lepromatous disease). Even shorter regimens using the above drugs are being developed, and used in some parts of the world, and in some areas patients with only one skin lesion are treated with only a single dose of medication. Several other drugs, minocycline, oflaxacin, and clarithromycin, have also been found effective for treatment and are used in cases in which there are allergies or intolerance to the three commonly used drugs.Patients with mild reactions, as described above, can be treated symptomatically with analgesics, but most cases will also require prednisone or similar drugs for control of the reactions. These may need to be given for many months at times. The drug thalidomide (Thalomid) has been approved by the FDA as a treatment for erythema nodosum leprosum (ENL), an inflammatory complication sometimes associated with leprosy that results in painful skin lesions. It is not effective in reversal reaction and does not kill bacteria. Thalidomide can have severe effects on a developing fetus and must be administered with extreme caution. It cannot generally be given to women of childbearing potential.Ocular complications of erythema nodosum leprosum (ENL) must be treated promptly to prevent permanent damage to the eyes. Local atropine and hydrocortisone eye drops may be used to keep the pupils dilated and reduce the inflammation until the reaction subsides. Patients with corneal dryness are treated with eye drops and substitutes for the eye's natural lubricants.Leprosy can be cured, and most disabilities and deformities can be prevented. Contrary to common perceptions, leprosy does not cause fingers and toes to drop off. The loss of fingers and toes that is sometimes seen is not due to the leprosy infection but to injuries that occur because of nerve damage and loss of feeling in the extremities. These injuries may become secondarily infected with other kinds of bacteria and cause the toes or fingers to lose infected bone and ultimately shorten. If the injuries can be prevented, much of the disability will not occur. The most important thing that can be done to prevent permanent disability is to diagnose and treat patients at the very earliest stages of the disease. They need to be started on appropriate drugs to kill the bacteria, and reactions must be treated promptly if they occur. For those who already have had some nerve damage, health education in the care of hands, feet, and eyes is very important to prevent further injury and deformity.Some people with leprosy may benefit from special shoes that compensate for loss of sensation in the feet. Gloves or special tools can be used to prevent injury to hands that have lost sensation. Surgery may be necessary to treat eye problems or correct certain deformities of the hands and feet. The goal of surgery is to improve function and the quality of life.
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Therapies of Leprosy. TreatmentLeprosy is a treatable and curable disease. The vast majority of patients can take their medication at home and continue their regular work and other activities. Patients with leprosy do not need to be isolated. It is important to note that the drugs used to treat leprosy are very effective in killing the bacteria, and patients on treatment are not infectious and do not spread the disease.The currently available drugs are very effective, and treatment is much shorter than was common 20 years ago. The major drugs are dapsone, rifampin, and clofazimine. Dapsone and rifampin can be given for six months for patients with PB disease (indeterminate, tuberculoid or borderline tuberculoid disease), and dapsone, rifampin, and clofazimine are given for two years for patients with MB disease (midborderline, borderline lepromatous and lepromatous disease). Even shorter regimens using the above drugs are being developed, and used in some parts of the world, and in some areas patients with only one skin lesion are treated with only a single dose of medication. Several other drugs, minocycline, oflaxacin, and clarithromycin, have also been found effective for treatment and are used in cases in which there are allergies or intolerance to the three commonly used drugs.Patients with mild reactions, as described above, can be treated symptomatically with analgesics, but most cases will also require prednisone or similar drugs for control of the reactions. These may need to be given for many months at times. The drug thalidomide (Thalomid) has been approved by the FDA as a treatment for erythema nodosum leprosum (ENL), an inflammatory complication sometimes associated with leprosy that results in painful skin lesions. It is not effective in reversal reaction and does not kill bacteria. Thalidomide can have severe effects on a developing fetus and must be administered with extreme caution. It cannot generally be given to women of childbearing potential.Ocular complications of erythema nodosum leprosum (ENL) must be treated promptly to prevent permanent damage to the eyes. Local atropine and hydrocortisone eye drops may be used to keep the pupils dilated and reduce the inflammation until the reaction subsides. Patients with corneal dryness are treated with eye drops and substitutes for the eye's natural lubricants.Leprosy can be cured, and most disabilities and deformities can be prevented. Contrary to common perceptions, leprosy does not cause fingers and toes to drop off. The loss of fingers and toes that is sometimes seen is not due to the leprosy infection but to injuries that occur because of nerve damage and loss of feeling in the extremities. These injuries may become secondarily infected with other kinds of bacteria and cause the toes or fingers to lose infected bone and ultimately shorten. If the injuries can be prevented, much of the disability will not occur. The most important thing that can be done to prevent permanent disability is to diagnose and treat patients at the very earliest stages of the disease. They need to be started on appropriate drugs to kill the bacteria, and reactions must be treated promptly if they occur. For those who already have had some nerve damage, health education in the care of hands, feet, and eyes is very important to prevent further injury and deformity.Some people with leprosy may benefit from special shoes that compensate for loss of sensation in the feet. Gloves or special tools can be used to prevent injury to hands that have lost sensation. Surgery may be necessary to treat eye problems or correct certain deformities of the hands and feet. The goal of surgery is to improve function and the quality of life.
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Leprosy
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nord_713_0
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Overview of Leptospirosis
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Leptospirosis is an infectious disease that affects humans and animals. It results in a wide range of symptoms, and some people may have no symptoms at all. It is caused by a spiral-shaped bacterium (spirochete). Symptoms include high fever, chills, muscle aches, headache, vomiting, diarrhea, and jaundice (yellow skin and eyes).A definitive diagnosis requires laboratory testing of a blood or urine sample. Early detection is important because the disease can cause serious complications if not treated early in its course. These include kidney damage (nephrosis), meningitis (inflammation of the tissue around the brain or spinal cord), respiratory distress and/or liver failure.
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Overview of Leptospirosis. Leptospirosis is an infectious disease that affects humans and animals. It results in a wide range of symptoms, and some people may have no symptoms at all. It is caused by a spiral-shaped bacterium (spirochete). Symptoms include high fever, chills, muscle aches, headache, vomiting, diarrhea, and jaundice (yellow skin and eyes).A definitive diagnosis requires laboratory testing of a blood or urine sample. Early detection is important because the disease can cause serious complications if not treated early in its course. These include kidney damage (nephrosis), meningitis (inflammation of the tissue around the brain or spinal cord), respiratory distress and/or liver failure.
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Leptospirosis
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nord_713_1
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Symptoms of Leptospirosis
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The symptoms of leptospirosis vary considerably. Some people may experience no symptoms at all. Some may experience moderate or more severe flu-like symptoms. Some may experience very serious complications if the disease is not treated. The disorder characteristically occurs in two phases. The septocemic phase starts abruptly with headache, pain behind the eyeball (retroorbital), lack of appetite (anorexia), severe muscle aches, chills, sweating, nausea, vomiting, and fever. Constipation, diarrhea, symptoms of the common cold, coughing, chest pain, a stiff neck, and difficulty breathing (dyspnea) may also occur. Enlargement of the spleen (splenomegaly) and liver (hepatomegaly) are uncommon, but may occur. This phase usually lasts four to nine days, with recurrent chills and fever that spikes to over 39 degrees C (102 F), and then abates.The sixth to 12th day of illness marks the immune (or second) phase of leptospirosis. Antibodies appear in the blood serum. Fever and earlier symptoms may recur, and symptoms of irritated membranes lining the brain (meninges) may develop. Examination of the cerebrospinal fluid after the seventh day shows a greater than normal number of cells (pleocytosis) in at least 50 percent of patients. Inflammation of the iris and the ciliary body behind the iris (iridocyclitis), the optic nerve (optic neuritis), and peripheral disease of the nerves (neuropathy) may occur infrequently. If acquired during pregnancy, leptospirosis may cause abortion, even during the period of convalescence.
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Symptoms of Leptospirosis. The symptoms of leptospirosis vary considerably. Some people may experience no symptoms at all. Some may experience moderate or more severe flu-like symptoms. Some may experience very serious complications if the disease is not treated. The disorder characteristically occurs in two phases. The septocemic phase starts abruptly with headache, pain behind the eyeball (retroorbital), lack of appetite (anorexia), severe muscle aches, chills, sweating, nausea, vomiting, and fever. Constipation, diarrhea, symptoms of the common cold, coughing, chest pain, a stiff neck, and difficulty breathing (dyspnea) may also occur. Enlargement of the spleen (splenomegaly) and liver (hepatomegaly) are uncommon, but may occur. This phase usually lasts four to nine days, with recurrent chills and fever that spikes to over 39 degrees C (102 F), and then abates.The sixth to 12th day of illness marks the immune (or second) phase of leptospirosis. Antibodies appear in the blood serum. Fever and earlier symptoms may recur, and symptoms of irritated membranes lining the brain (meninges) may develop. Examination of the cerebrospinal fluid after the seventh day shows a greater than normal number of cells (pleocytosis) in at least 50 percent of patients. Inflammation of the iris and the ciliary body behind the iris (iridocyclitis), the optic nerve (optic neuritis), and peripheral disease of the nerves (neuropathy) may occur infrequently. If acquired during pregnancy, leptospirosis may cause abortion, even during the period of convalescence.
| 713 |
Leptospirosis
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Causes of Leptospirosis
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Humans usually become infected through contact with water, food or soil containing urine from infected animals. The bacterium associated with the disease, Leptospira, can be found in the urine of many different animals, such as dogs, cats, cattle, horses, pigs, and, especially, rodents. The disease is transmitted to humans when infected urine enters the body when one swallows contaminated food or water or through breaks in the skin or contact with mucosal surfaces such as the eyes or nose. The disease is not known to be spread from person to person.The usual period of time between exposure to the bacterium and appearance of the disease is from two to 20 days.
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Causes of Leptospirosis. Humans usually become infected through contact with water, food or soil containing urine from infected animals. The bacterium associated with the disease, Leptospira, can be found in the urine of many different animals, such as dogs, cats, cattle, horses, pigs, and, especially, rodents. The disease is transmitted to humans when infected urine enters the body when one swallows contaminated food or water or through breaks in the skin or contact with mucosal surfaces such as the eyes or nose. The disease is not known to be spread from person to person.The usual period of time between exposure to the bacterium and appearance of the disease is from two to 20 days.
| 713 |
Leptospirosis
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Affects of Leptospirosis
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While leptospirosis is rare in the United States, it is common through tropical and semitropical regions. It can affect individuals of all ages. At least 75 percent of individuals with leptospirosis are male, mainly because workers in jobs that are at risk of the infection are more often held by males. The infection is an occupational disorder affecting farmers, veterinarians, workers in slaughter houses and sewer workers. However, many affected individuals are thought to be exposed incidentally during recreational activities, such as swimming in water contaminated by the urine of infected animals.In recent years, several cases of leptospirosis have been reported in urban areas, especially inner city neighborhoods. It is thought that these areas are infested with rats that carry the infection.
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Affects of Leptospirosis. While leptospirosis is rare in the United States, it is common through tropical and semitropical regions. It can affect individuals of all ages. At least 75 percent of individuals with leptospirosis are male, mainly because workers in jobs that are at risk of the infection are more often held by males. The infection is an occupational disorder affecting farmers, veterinarians, workers in slaughter houses and sewer workers. However, many affected individuals are thought to be exposed incidentally during recreational activities, such as swimming in water contaminated by the urine of infected animals.In recent years, several cases of leptospirosis have been reported in urban areas, especially inner city neighborhoods. It is thought that these areas are infested with rats that carry the infection.
| 713 |
Leptospirosis
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Related disorders of Leptospirosis
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Many types of bacterial infections may cause fever and other symptoms similar to the symptoms of leptospirosis.Weil syndrome is a severe form of bacterial infection caused by Leptospira bacteria (Leptospirosis) causing abnormal liver and kidney function. (For more information on this disorder, choose “Weil Syndrome” as your search term in the Rare Disease Database.)Meningitis is an infection of the membrane lining the skull or the spinal cavity (meninges) by either bacteria or viruses. (For more information on this disorder, choose “Meningitis” as your search term in the Rare Disease Database.)
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Related disorders of Leptospirosis. Many types of bacterial infections may cause fever and other symptoms similar to the symptoms of leptospirosis.Weil syndrome is a severe form of bacterial infection caused by Leptospira bacteria (Leptospirosis) causing abnormal liver and kidney function. (For more information on this disorder, choose “Weil Syndrome” as your search term in the Rare Disease Database.)Meningitis is an infection of the membrane lining the skull or the spinal cavity (meninges) by either bacteria or viruses. (For more information on this disorder, choose “Meningitis” as your search term in the Rare Disease Database.)
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Leptospirosis
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Diagnosis of Leptospirosis
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Diagnosis may be made during the early stage of the infection (days 1-7) by culturing the Leptospira bacterium from body fluids. From days 4 through 10, the cerebrospinal fluid is cultured, and after day 10, the patient's urine may be cultured. There are other tests of the blood and immune system that may be performed.
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Diagnosis of Leptospirosis. Diagnosis may be made during the early stage of the infection (days 1-7) by culturing the Leptospira bacterium from body fluids. From days 4 through 10, the cerebrospinal fluid is cultured, and after day 10, the patient's urine may be cultured. There are other tests of the blood and immune system that may be performed.
| 713 |
Leptospirosis
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Therapies of Leptospirosis
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TreatmentLeptospirosis is treated with antibiotics such as penicillin, oral doxycycline, streptomycin, chloramphenicol, and erythromycin.Mechanical ventilation has been used successfully in treating respiratory distress in leptospirosis patients.Peritoneal dialysis in combination with treatment with antibiotics has been used successfully to treat severe liver and kidney failure in patients with leptospirosis.PreventionThe risk of infection may be greatly reduced by not swimming in waters that may be contaminated with animal urine. People who work in jobs where this might be an occupational hazard, should wear appropriate protective clothing to avoid skin contact if possible. Pet-owners should be aware of the possibility of infection of household pets.
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Therapies of Leptospirosis. TreatmentLeptospirosis is treated with antibiotics such as penicillin, oral doxycycline, streptomycin, chloramphenicol, and erythromycin.Mechanical ventilation has been used successfully in treating respiratory distress in leptospirosis patients.Peritoneal dialysis in combination with treatment with antibiotics has been used successfully to treat severe liver and kidney failure in patients with leptospirosis.PreventionThe risk of infection may be greatly reduced by not swimming in waters that may be contaminated with animal urine. People who work in jobs where this might be an occupational hazard, should wear appropriate protective clothing to avoid skin contact if possible. Pet-owners should be aware of the possibility of infection of household pets.
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Leptospirosis
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nord_714_0
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Overview of Leri Pleonosteosis
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Leri Pleonosteosis is an extremely rare inherited disorder characterized by unusual, flattened facial features, abnormalities of the hands and feet, skeletal malformations, short stature, and/or limitation of joint movements. Characteristic abnormalities of the hands and feet may include unusually broad and/or short thumbs and great toes (brachydactyly) that may be bent outward from the body (valgus position); as a result, the hands may have a “spade-shaped” appearance. Skeletal malformations may include knees that are bent backward (genu recurvitum) and abnormal enlargement of the cartilaginous structures that surround the upper portion of the spinal cord (posterior neural arches of the cervical vertebrae). In addition, affected individuals may develop thickened tissue on the palms (palmar) and forearms. Symptoms may vary from case to case. Leri pleonosteosis is inherited as an autosomal dominant genetic trait.
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Overview of Leri Pleonosteosis. Leri Pleonosteosis is an extremely rare inherited disorder characterized by unusual, flattened facial features, abnormalities of the hands and feet, skeletal malformations, short stature, and/or limitation of joint movements. Characteristic abnormalities of the hands and feet may include unusually broad and/or short thumbs and great toes (brachydactyly) that may be bent outward from the body (valgus position); as a result, the hands may have a “spade-shaped” appearance. Skeletal malformations may include knees that are bent backward (genu recurvitum) and abnormal enlargement of the cartilaginous structures that surround the upper portion of the spinal cord (posterior neural arches of the cervical vertebrae). In addition, affected individuals may develop thickened tissue on the palms (palmar) and forearms. Symptoms may vary from case to case. Leri pleonosteosis is inherited as an autosomal dominant genetic trait.
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Leri Pleonosteosis
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nord_714_1
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Symptoms of Leri Pleonosteosis
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Infants with this disorder typically have a flattened facial appearance that may be similar to that of infants with Down syndrome. In rare cases, affected infants may also have an abnormally narrow distance between the upper and lower eyelids (blepharophimosis) and/or an unusually small part of the eye through which light passes (microcornea).Children with Leri pleonosteosis may not grow at the expected rate and eventually exhibit short stature. They may also exhibit various skeletal abnormalities including stiff joints and, in severe cases, joints that are fixed in a permanently flexed position (contractures). In some cases, the cartilage that surrounds the upper portion of the spinal cord (posterior neural arches of the cervical vertebrae) may be unusually thick and overgrown. In addition, affected individuals may have knees that are bent backward (genu recurvatum). Such skeletal abnormalities may result in limitation of movement, and affected individuals may have an unusual shuffling, short-stepped manner of walking (gait).Other skeletal malformations associated with Leri pleonosteosis typically affect the hands and feet. Many infants with this disorder have abnormally short and/or broad fingers (brachydactyly), giving the hands a “spade-shaped” appearance; the toes may also be affected. In addition, the thumbs and great toes may be bent outward from the body (valgus position). In some cases, affected children may develop abnormally dense fibrous tissue (fasciae) on the palms, forearms, and/or feet. Overgrowth (hyperplasia) of fibrous tissue may, in some cases, cause compression of nerves of the feet and/or wrists, resulting in pain, tenderness, and/or other symptoms (e.g., Morton metatarsalgia and/or carpal tunnel syndrome). (For more information on these conditions, see the Related Disorders section of this report.) In some rare cases, affected individuals also develop compression of certain nerves of the upper part of the spinal cord.
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Symptoms of Leri Pleonosteosis. Infants with this disorder typically have a flattened facial appearance that may be similar to that of infants with Down syndrome. In rare cases, affected infants may also have an abnormally narrow distance between the upper and lower eyelids (blepharophimosis) and/or an unusually small part of the eye through which light passes (microcornea).Children with Leri pleonosteosis may not grow at the expected rate and eventually exhibit short stature. They may also exhibit various skeletal abnormalities including stiff joints and, in severe cases, joints that are fixed in a permanently flexed position (contractures). In some cases, the cartilage that surrounds the upper portion of the spinal cord (posterior neural arches of the cervical vertebrae) may be unusually thick and overgrown. In addition, affected individuals may have knees that are bent backward (genu recurvatum). Such skeletal abnormalities may result in limitation of movement, and affected individuals may have an unusual shuffling, short-stepped manner of walking (gait).Other skeletal malformations associated with Leri pleonosteosis typically affect the hands and feet. Many infants with this disorder have abnormally short and/or broad fingers (brachydactyly), giving the hands a “spade-shaped” appearance; the toes may also be affected. In addition, the thumbs and great toes may be bent outward from the body (valgus position). In some cases, affected children may develop abnormally dense fibrous tissue (fasciae) on the palms, forearms, and/or feet. Overgrowth (hyperplasia) of fibrous tissue may, in some cases, cause compression of nerves of the feet and/or wrists, resulting in pain, tenderness, and/or other symptoms (e.g., Morton metatarsalgia and/or carpal tunnel syndrome). (For more information on these conditions, see the Related Disorders section of this report.) In some rare cases, affected individuals also develop compression of certain nerves of the upper part of the spinal cord.
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Leri Pleonosteosis
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