Ocular pathology of GM2 gangliosidosis--Type 2 (Sandhoff's disease).

The introduction in recent years of more refined techniques for the isolation and characterization of biological lipids has led to the detection of a number of disorders which share with Tay-Sachs disease a disturbance of ganglioside metabolism. Gangliosides are sphingosine-containing glycolipids distinguished by the inclusion of neuraminic acid, and the various gangliosidoses are attributable to defects in the enzyme systems required for their degradation. Of the three disorders involving accumulation of the so-called GM2 ganglioside, Tay-Sachs disease (infantile amaurotic idiocy) is much the most common. Recent studies, however, have shown that GM2 ganglioside breakdown is dependent on hexosaminidase, a lysosomal enzyme which has two components referred to as A and B (Robinson and Stirling, I968), and that, whereas in Tay-Sachs disease the A component alone is deficient (Okada and O'Brien, I969), the entire enzyme is absent (Sandhoff, I969) in a related disorder first described by Sandhoff, Andreae, and Jatzkewitz (I968). This results in the accumulation, not only of GM2 ganglioside as in Tay-Sachs disease, but also of its neuraminic acid-free derivative (O'Brien, Okada, Ho, Fillerup, Veath, andAdams, I97I). The viscera in Sandhoff's disease accumulate a ceramide-based glycolipid, globoside, which is similarly dependent on hexosaminidase for its breakdown (O'Brien and others, I971). The clinical features and pathology of Sandhoff's and Tay-Sachs disease are virtually indistinguishable (Pilz, Sandhoff, andJatzkewitz, I966; O'Brien and others, I97I; Bain, Tateson, Anderson, and Cumings, 1972), and it is possible that a proportion of alleged Tay-Sachs cases, particularly in non-Jews, may in reality be examples of Sandhoff's disease. Reliable differentiation in life can be made only on the basis of serum and tissue hexosaminidase assay (Okada and O'Brien, I969; Okada, Veath, Leroy, and O'Brien, 197I; Bain and others, 1972). A full account of the clinical, pathological, and biochemical feature, excluding the ocular pathology, of Sandhoff's disease occurring in a Scottish family is given by Bain and others (1972). The present report concerns the ocular findings in one of their cases.