Nature of the Metabolic Defect

FIGURE 2. An electron micrograph of a typical neuronal cell from the brain of a patient with type I Gm2-gangliosidosis. Numerous membranous cytoplasmic bodies (MCB) may be seen in the cytoplasm. From Terry and Weiss, 1963. 

FIGURE 3. Typical isolated membranous cytoplasmic bodies (MCB). Magnification X 34,000. From Suzuki et al., 1969. 

In order to obtain a full understanding of the pathological biochemistry of Tay-Sachs disease, several considerations must be taken into account. Hexosaminidase B, which is present in the tissues of patients with GM2-gangliosidosis types I and III, can catalyze the hydrolysis of Ga2 produced by the Gm2-neuraminidase. Since the specific activity of this neuraminidase is normal in Tay-Sachs patients and the activity of the B-like enzyme is elevated (Sandhoff et aL, 1971), why does Gm2 accumulate at all  

TABLE I. Ganglioside Catabolism by Human Brain Lysosomes 

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Patients with type II GM2 gangliosidosis are characterized by the accumulation of Gm2 and its asialo derivative in neuronal cells. It is interesting that the amount of Ga2 accumulation in relation to Gm2 is greater than in type I disease. This finding may be related to the nature of the metabolic defect discussed in Section II, D. In type II patients, there is also a significantly higher accumulation of Gm2 in liver when compared to Tay-Sachs patients, where Gm2 accumulation is minimal (Kolodny, 1972). 

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