Disorders of Ganglioside Catabolism

Abstract

Reactions involved in the catabolism of gangliosides and related neutral glycosphingolipids have been intensively investigated in recent years because deficiencies in certain of the enzymes catalyzing these reactions lead to characteristic neurological disorders known as the lipidoses (Brady, 1966, 1972, 1973). It is presently believed that the catabolism of a ganglioside proceeds stepwise from the nonreducing terminus of the carbohydrate portion of the molecule to the ceramide moiety* (Figure 1), (Tallman and Brady, 1973). The enzymes involved in this process are located in the lysosomes and exhibit properties characteristic of such enzymes. Of the six different enzymes known to participate in ganglioside breakdown, clinical disorders associated with deficiencies in five of these separate reactions have been found. Only a neuraminidase deficiency has not been described (see below). Deficiencies in glucocerebrosidase [Gaucher’s disease (Brady et al; 1965)], and lactosylceramide-β-galactosidase (Dawson and Stein, 1970) are known and discussed elsewhere (Brady, 1973). In this chapter we shall focus on the deficiencies leading to ganglioside accumulation. (See Chapter 2, Table I, for a listing of ganglioside structures and abbreviations.)