The Morphogenesis and Biochemical Characteristics of Ceroid Isolated from Cases of Neuronal Ceroid-Lipofuscinosis

Abstract

Two distinctly different groups of disorders have emerged from the conditions generically classified as amaurotic familial idiocies. One is characterized by grossly abnormal profiles for cerebral sphingolipids, for example the G_M1 and G_M2 gangliosides. The other group is composed of patients with normal sphingolipid profiles, but with neuronal accumulation of lipopigments of the ceroid-lipofuscin type. The sphingolipidoses have been shown by a number of investigators to meet the classic concept of Hers (1965) for lysosomal diseases. This view has been repeatedly reinforced by continuing studies which show the lack or reduction of specific hydrolases, resulting in the accumulation of biochemical compounds which cannot be degraded to metabolically utilizable substances. The concept of lysosomal diseases has led many investigators to search for a single accumulating lipid or a deficient hydrolytic enzyme unique to neuronal ceroid-lipofuscinoses. Since many of the lysosomal disorders became better understood by the elucidation of the chemical properties of a specific lipid, present in unphysiologically large quantities, the pronouncement by Donahue et al. (1966) before this group, that the “chemical analysis of cytoplasmic lipopigment granules (from the brains of patients with Batten’s disease) will contribute little towards an understanding of this disease” was decidedly unwise. Although it is correct, that autofluorescent lipopigments lack chemical specificity and result from a great variety of pathogenetic situations (Porta and Hartroft, 1969), Donahue et al. (1966) failed to recognize the distinct possibility, that certain repetitive patterns in the chemical composition and ultrastructure of these residual bodies may indicate a specific formative pathogenesis. On the strength of this argument, we developed methods to isolate lipopigments in pure preparations and the first results have proved already the soundness of this concept. As it turned out, the previously held concept of a close relationship between lipofuscin and ceroid had to be abandoned and replaced by the theses that these classes of lipopigment are distinctly different entities, albeit both represent residual bodies and both contain polymeric substances (Siakotos et al., 1970).