Tay-Sachs Disease

The most common of the lipid storage diseases, Tay-Sachs disease results from a congenital deficiency of the enzyme hexosaminidase A. It’s characterized by progressive mental and motor deterioration and is usually fatal before age 5, although some adolescents and adults with variations of hexosaminidase A deficiency have been noted.

Causes
Tay-Sachs disease (also known as GM2 gangliosidosis) is an autosomal recessive disorder in which the enzyme hexosaminidase A is virtually absent or deficient. This enzyme is necessary for metabolism of gangliosides, water-soluble glycolipids found primarily in central nervous system (CNS) tissues. Without hexosaminidase A, accumulating lipid pigments distend and progressively destroy and demyelinate CNS cells.
Tay-Sachs disease strikes persons of Eastern European Jewish (Ashkenazi) ancestry more often than the general population, occurring in about 1 in 2,500 live births in this ethnic group. About 1 in 25 Ashkenazi Jews are heterozygous carriers.

Signs and symptoms
A neonate with classic Tay-Sachs disease appears normal at birth, although he may have an exaggerated Moro reflex. By age 3 to 6 months, he becomes apathetic and responds only to loud sounds. His neck, trunk, arm, and leg muscles grow weaker, and soon he can’t sit up or lift his head. He has difficulty turning over, can’t grasp objects, and has progressive vision loss.
By age 18 months, the infant is usually deaf and blind and has seizures, generalized paralysis, and spasticity. His pupils are dilated and don’t react to light. Decerebrate rigidity and a vegetative state follow. The child suffers recurrent bronchopneumonia after age 2 and usually dies before age 5. A child who survives may develop ataxia and progressive motor retardation between ages 2 and 8.
The “juvenile” form of Tay-Sachs disease generally appears between ages 2 and 5 as a progressive deterioration of psychomotor skills and gait. Patients with this type can survive to adulthood.

Diagnosis
Typical clinical features point to Tay-Sachs disease, but serum analysis showing deficient hexosaminidase A is the key to diagnosis. An ophthalmologic examination showing optic nerve atrophy and a distinctive cherry-red spot on the retina supports the diagnosis. (The cherry-red spot may be absent in the juvenile form.)
Carrier screening is essential for all couples when at least one partner is of Ashkenazi Jewish ancestry and for others with a family history of the disease. A blood test evaluating hexosaminidase A levels can identify carriers. Amniocentesis or chorionic villus sampling can detect hexosaminidase A deficiency in the fetus.
For two-carrier parents utilizing in-vitro fertilization to achieve pregnancies, preimplantation genetic testing has been attempted with some success. Healthy embryos are transferred to the woman’s uterus.

Treatment
Tay-Sachs disease has no known cure. Supportive treatment includes tube feedings of nutritional supplements, suctioning and postural drainage to remove pharyngeal secretions, skin care to prevent pressure ulcers in bedridden children, and mild laxatives to relieve neurogenic constipation. Anticonvulsants usually fail to prevent seizures. Because these children need constant physical care, many parents have full-time skilled home nursing care or place them in long-term special care facilities.

Special considerations
Your most important job is to help the family deal with inevitably progressive illness and death.
Offer carrier testing to all couples from high-risk ethnic groups.
Refer the parents for genetic counseling, and stress the importance of amniocentesis in future pregnancies. Refer siblings for screening to determine whether they’re carriers. If they are carriers and are adults, refer them for genetic counseling, but stress that there is no danger of transmitting the disease to offspring if they don’t marry another carrier.
Because the parents of an affected child may feel excessive stress or guilt because of the child’s illness and the emotional and financial burden it places on them, refer them for psychological counseling if indicated.
If the parents care for their child at home, teach them how to do suctioning, postural drainage, and tube feeding. Also teach them how to provide good skin care to prevent pressure ulcers.