Ganglioside catabolism in hexosaminidase A-deficient adults

TAY-SACHS disease is an inborn error of glycosphingolipid metabolism characterised by the accumulation of N-acetyl-galactosaminyl - (N-acetylneuraminyl) - galactosylglucosylcera -mide (G_M2) and N-acetylgalactosaminylgalactosylglucosyl-ceramide (G_A2) in various tissues of affected individuals¹. A defect in the removal of N-acetylgalactosamine from G_M2, catalysed by a hexosaminidase, has been demonstrated as the underlying deficiency in all forms of G _M2-gangliosidosis^2,3. In Tay-Sachs disease this defect has been associated with the absence of one (the A form) of the two major isozymes of β-N-acetylhexosaminidase (Hex A and Hex B)⁴. Hex A can be differentiated from Hex B in serum, leukocytes, cultured skin and amniotic fluid cells, and urine by using various physical characteristics of these enzymes⁵. The smaller proportion of A relative to B is the basis of screening for heterozygous carriers of Tay-Sachs disease⁶.