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.
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