Tay–Sachs disease (abbreviated TSD, also known as GM2 gangliosidosis or Hexosaminidase A deficiency) is an autosomal recessive genetic disorder. 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. Tay–Sachs disease is rare, and other autosomal recessive 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. 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.
Signs and symptoms
Tay–Sachs disease is classified in variant forms, based on the time of onset of neurological symptoms. The variant forms reflect diversity in the mutation baseInfantile TSD. Infants with Tay–Sachs disease appear to develop normally for the first six months after birth. Then, as nerve cells become distended with gangliosides, a relentless deterioration of mental and physical abilities occurs. The child becomes blind, deaf, and unable to swallow. Death usually occurs before the age of four.
Juvenile TSD. Extremely rare, juvenile Tay
The best accepted of the lipid accumulator diseases, Tay-Sachs ache after-effects from a complete absence of the agitator hexosaminidase A. It’s characterized by accelerating brainy and motor abasement and is usually baleful afore age 5, although some adolescents and adults with variations of hexosaminidase A absence accept been noted.
Causes
Tay-Sachs ache (also accepted as GM2 gangliosidosis) is an autosomal backward anarchy in which the agitator hexosaminidase A is around absent or deficient. This agitator is all-important for metabolism of gangliosides, water-soluble glycolipids begin primarily in axial afraid arrangement (CNS) tissues. Without hexosaminidase A, accumulating lipid pigments amplify and progressively abort and demyelinate CNS cells.
Tay-Sachs ache strikes bodies of Eastern European Jewish (Ashkenazi) ancestor added about than the accepted population, occurring in about 1 in 2,500 alive births in this indigenous group. About 1 in 25 Ashkenazi Jews are heterozygous carriers.
Signs and symptoms
A adolescent with archetypal Tay-Sachs ache appears accustomed at birth, although he may accept an abstract Moro reflex. By age 3 to 6 months, he becomes blah and responds alone to loud sounds. His neck, trunk, arm, and leg anatomy abound weaker, and anon he can’t sit up or lift his head. He has adversity axis over, can’t butt objects, and has accelerating eyes loss.
By age 18 months, the baby is usually deafened and dark and has seizures, ambiguous paralysis, and spasticity. His pupils are aggrandized and don’t acknowledge to light. Decerebrate acerbity and a abundant accompaniment follow. The adolescent suffers alternate bronchopneumonia afterwards age 2 and usually dies afore age 5. A adolescent who survives may advance anarchy and accelerating motor amentia amid ages 2 and 8.
The “juvenile” anatomy of Tay-Sachs ache about appears amid ages 2 and 5 as a accelerating abasement of psychomotor abilities and gait. Patients with this blazon can survive to adulthood.
Diagnosis
Typical analytic appearance point to Tay-Sachs disease, but serum assay assuming amiss hexosaminidase A is the key to diagnosis. An ophthalmologic assay assuming optic assumption decline and a characteristic cherry-red atom on the retina supports the diagnosis. (The cherry-red atom may be absent in the adolescent form.)
Carrier screening is capital for all couples back at atomic one accomplice is of Ashkenazi Jewish ancestor and for others with a ancestors history of the disease. A claret analysis evaluating hexosaminidase A levels can analyze carriers. Amniocentesis or chorionic beard sampling can ascertain hexosaminidase A absence in the fetus.
For two-carrier parents utilizing in-vitro fertilization to accomplish pregnancies, preimplantation abiogenetic testing has been attempted with some success. Healthy embryos are transferred to the woman’s uterus.
Treatment
Tay-Sachs ache has no accepted cure. Supportive analysis includes tube feedings of comestible supplements, suctioning and postural arising to abolish pharyngeal secretions, bark affliction to anticipate accountability ulcers in bedfast children, and balmy laxatives to abate neurogenic constipation. Anticonvulsants usually abort to anticipate seizures. Because these accouchement charge connected concrete care, abounding parents accept full-time accomplished home nursing affliction or abode them in abiding appropriate affliction facilities.
Special considerations
Your best important job is to advice the ancestors accord with accordingly accelerating affliction and death.
Offer carrier testing to all couples from high-risk indigenous groups.
Accredit the parents for abiogenetic counseling, and accent the accent of amniocentesis in approaching pregnancies. Accredit ancestors for screening to actuate whether they’re carriers. If they are carriers and are adults, accredit them for abiogenetic counseling, but accent that there is no crisis of transmitting the ache to baby if they don’t ally addition carrier.
Because the parents of an afflicted adolescent may feel boundless accent or answerability because of the child’s affliction and the affecting and banking accountability it places on them, accredit them for cerebral counseling if indicated.
If the parents affliction for their adolescent at home, advise them how to do suctioning, postural drainage, and tube feeding. Additionally advise them how to accommodate acceptable bark affliction to anticipate accountability ulcers.
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