Tay-Sachs disease.

Abstract

Tay-Sachs disease is an autosomal recessive disease caused by a deficiency of β-hexosaminidase A, the lysosomal enzyme that normally degrades GM2 ganglioside. As a result, GM2 ganglioside accumulates in the lysosomes of nerve cells. The disease is one of a family of lysosomal storage disorders known as GM2 gangliosidoses, each determined by the specific peptide (a and β subunits of β-hexosaminidase A and the GM2 activator protein) that is defective in the degradation of GM2 ganglioside. 1 While Tay-Sachs disease commonly refers to the classic infantile form of this GM2 gangliosidosis (also called type 1 GM2 gangliosidosis), wherein β-hexosaminidase A is virtually absent, juvenile and late-onset forms also occur when there is residual enzymatic activity. The highest carrier rate has been among Ashkenazic Jews, although the incidence has decreased among this population because of widespread carrier screening, while clusters remain among certain French Canadian and Cajun populations. This article in the Seminal Citations series focuses on early descriptions of the disease and key developments in biochemistry, genetics, testing, and treatment.