Tay‐Sachs Disease

Summary A detailed histological and biochemical study was performed on autopsy material from an advanced case of typical infantile amaurotic idiocy in a non‐Jewish boy. Many nerve cells were distended by accumulated glycolipids, but in others no signs of storage were seen in the cell body while large amounts of lipids had accumulated in balloon‐shaped swellings of the axons at varying distances from the perikaryon, indicating an axonal transport of the gangliosides. The glial cells contained materials which gave a primary fluores cence and had histochemical properties characteristic for lipofuscin. Histochemically the visceral organs did not show any glycolipid storage of the same type as in the nervous system. Chemical analysis showed an aecuniulation in brain of ceramide sialyl‐N‐trihesoside (ganglioside G M2 ) which has been found in all other typical cases studied. There was a very advanced degeneration of myelin sheathsand most neutralglycolipidsin brain had similar ceramideportion as gangliosicles which suggest an intimate metabolic relationship. In liver and spleen a ganglioside with the same carbohydrate moiety as in brain ganglioside was isolated. Its ceramide portion had a composition that was intermediate between that of gangliosides from the nervous system and from normal liver and spleen. Therefore, it is proposed that one part of the liver gangliosisides was for med in the nervous system and transported to these organs and the other part is formed in situ . The finding of Tay‐Sachs ganglioside with the same fatty acids as in norinal liver gangliosides suggests that Tay‐Sachs disease is a generalized disorder. The enzymic lesion in Tay‐Sachs disease is discussed. It is stated that a lack of a glycolipid β‐N‐acetylgalactosaminidase is still the most plausible explanation for the biochemical changes in this disease.