Metabolic Diseases

. The neuronal ceroid-lipofuscinoses (NCL) are considered lysosomal disorders because of the accumulation of autofluorescent lipopigment residual bodies in nerve cells and in numerous other nonneuronal and extracerebral cells. However, progress in the elucidation of morphogenesis, pathogenesis, biochemistry and mutational genetics based on the principle of "forward" genetics had, compared to that in lysosoma1 disorders, not been achieved in the NCL, because the accruing lipopigments have turned out to be resistent to complete biochemical analysis and, thus, have not permitted identification of NCL-specific enzyme defects and their genetic analysis. Conversely, the principle of "reverse" genetics 1 or positional cloning has procured recent striking advances in the NCL even resulting in a gene-based reclassification of clinical types of NCL, i.e. infantile NCL = CLN1, late-infantile NCL = CLN2, juvenile NCL = CLN3, adult NCL = CLN4, Finnish late-infantile variant = CLNS, and earlyjuvenile NCL = CLN6, with respective genes localized to five different chromosomes, except the one for CLN4.