Tay–Sachs disease

Medical condition Tay-Sachs disease (abbreviated TSD , also known as GM2 gangliosidosis or Hexosaminidase A deficiency ) is an autosomal recessive genetic disorder . In its most common variant, known as infantile Tay-Sachs disease, it causes a relentless deterioration of mental and physical abilities that commences around six months of age and usually results in death by the age of four. It is caused by a genetic defect in a single gene with one defective copy of that gene inherited from each parent. The disease occurs when harmful quantities of gangliosides accumulate in the nerve cells of the brain , eventually leading to the premature death of those cells. There is currently no cure or treatment. Tay-Sachs disease is rare. Other autosomal disorders such as cystic fibrosis and sickle cell anemia are far more common. The disease is named after British ophthalmologist Warren Tay , who first described the red spot on the retina of the eye in 1881, and the American neurologist Bernard Sachs of Mount Sinai Hospital, New York who described the cellular changes of Tay-Sachs and noted an increased prevalence in the Eastern European Jewish ( Ashkenazi ) population in 1887. Research in the late 20th century demonstrated that Tay-Sachs disease is caused by a genetic mutation on the HEXA gene on chromosome 15 . A large number of HEXA mutations have been discovered, and new ones are still being reported. These mutations reach significant frequencies in several populations. French Canadians of southeastern Quebec have a carrier frequency similar to Ashkenazi Jews, but they carry a different mutation. Many Cajuns of southern Louisiana carry the same mutation that is most common in Ashkenazi Jews . Most HEXA mutations are rare, and do not occur in genetically isolated populations. The disease can potentially occur from the inheritance of two unrelated mutations in the HEXA gene.

Medical condition Tay–Sachs disease (also known as GM2 gangliosidosis or hexosaminidase A deficiency ) is a rare autosomal recessive genetic disorder . In its most common variant (known as infantile Tay–Sachs disease), it causes a progressive deterioration of nerve cells and of mental and physical abilities that begins around six months of age and usually results in death by the age of four. The disease occurs when harmful quantities of cell membrane components known as gangliosides accumulate in the brain 's nerve cells, eventually leading to the premature death of the cells. A ganglioside is a form of sphingolipid , which makes Tay–Sachs disease a member of the sphingolipidoses . There is no known cure or treatment. The disease is named after the British ophthalmologist Waren Tay , who in 1881 first described a symptomatic red spot on the retina of the eye; and after the American neurologist Bernard Sachs of Mount Sinai Hospital, New York , who described in 1887 the cellular changes of Tay–Sachs disease and noted an increased disease prevalence in Ashkenazi Jewish people. Research in the late 20th century demonstrated that Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on (human) chromosome 15 . A large number of HEXA mutations have been discovered, and new ones are still being reported. These mutations reach significant frequencies in specific populations. French Canadians of southeastern Quebec have a carrier frequency similar to that seen in Ashkenazi Jews, but carry a different mutation. Cajuns of southern Louisiana carry the same mutation that is seen most commonly in Ashkenazi Jews. HEXA mutations are rare and are most seen in genetically isolated populations. Tay–Sachs can occur from the inheritance of either two similar, or two unrelated, causative mutations in the HEXA gene. As an autosomal recessive disorder, two Tay–Sachs alleles are required for an individual to exhibit symptoms of the disease. Carriers of a single Tay–Sachs allele do not exhibit symptoms of the disease but appear to be protected to some extent against tuberculosis . This accounts for the persistence of the allele in certain populations in that it confers a selective advantage —in other words, being a heterozygote is advantageous .

Medical condition Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord . The most common form is infantile Tay–Sachs disease which becomes apparent around three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures , hearing loss , and inability to move , with death usually occurring by the age of four. Less commonly, the disease may occur in later childhood or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by age 15. Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15 , which codes for a subunit of the hexosaminidase enzyme known as hexosaminidase A. It is inherited from a person's parents in an autosomal recessive manner. The mutation disrupts the activity of the enzyme, which results in the buildup of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or genetic testing . Tay–Sachs disease is a type of GM2 gangliosidosis and sphingolipidosis . The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews , French Canadians of southeastern Quebec , the Old Order Amish of Pennsylvania , and the Cajuns of southern Louisiana , the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected. The disease is named after British opthalmologist Waren Tay , who in 1881 first described a symptomatic red spot on the retina of the eye; and American neurologist Bernard Sachs , who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from tuberculosis , explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments. NORD (National Organization for Rare Disorders) . 2017. Molecular Medicine: An Introduction . Disorders of Lipid Metabolism . Vogel and Motulsky's Human Genetics: Problems and Approaches (3 ed.).

Human medical condition Medical condition Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord . The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures , hearing loss , and inability to move , with death usually occurring by the age of three to five. Less commonly, the disease may occur in later childhood or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by age 15. Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15 , which codes a subunit of the hexosaminidase enzyme known as hexosaminidase A. It is inherited in an autosomal recessive manner. The mutation disrupts the activity of the enzyme, which results in the build-up of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or genetic testing . Tay–Sachs disease is a type of GM2 gangliosidosis and sphingolipidosis . The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews , French Canadians of southeastern Quebec , the Old Order Amish of Pennsylvania , and the Cajuns of southern Louisiana , the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected. The disease is named after British ophthalmologist Waren Tay , who in 1881 first described a symptomatic red spot on the retina of the eye; and American neurologist Bernard Sachs , who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from tuberculosis , explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments. NORD (National Organization for Rare Disorders) . 2017. Molecular Medicine: An Introduction . Disorders of Lipid Metabolism . Vogel and Motulsky's Human Genetics: Problems and Approaches (3 ed.).

Rare, severe disease of lysosomal storage Medical condition Tay–Sachs disease is an inherited fatal lysosomal storage disease that results in the destruction of nerve cells in the brain and spinal cord . The most common form is infantile Tay–Sachs disease, which becomes apparent around the age of three to six months of age, with the infant losing the ability to turn over, sit, or crawl. This is then followed by seizures , hearing loss , and inability to move , with death usually occurring by the age of three to five. Less commonly, the disease may occur later in childhood, adolescence, or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by the age of 15. Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15 , which codes a subunit of the hexosaminidase enzyme known as hexosaminidase A. It is inherited in an autosomal recessive manner. The mutation disrupts the activity of the enzyme, which results in the build-up of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or genetic testing . Tay–Sachs disease is a type of GM2 gangliosidosis and sphingolipidosis . The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialties as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews , French Canadians of southeastern Quebec , the Old Order Amish of Pennsylvania , and the Cajuns of southern Louisiana , the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected. The disease is named after British ophthalmologist Waren Tay , who in 1881 first described a symptomatic red spot on the retina of the eye; and American neurologist Bernard Sachs , who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from tuberculosis , explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments. NORD (National Organization for Rare Disorders) . 2017. Molecular Medicine: An Introduction . Disorders of Lipid Metabolism . Vogel and Motulsky's Human Genetics: Problems and Approaches (3 ed.).