Reevaluation of neuronal ceroid lipofuscinoses: Atypical juvenile onset may be the result of CLN2 mutations

This study describes the phenotype/genotype analyses of 56 probands with a juvenile onset, some of which had atypical features of neuronal ceroid lipo fuscinosis, collected at the New York State Institute for Basic Research (I BR). In this group, we found probands with abundant curvilinear profiles in lysosomal storage material, deficiency of pepstatin-insensitive peptidase, and mutations in the CLN2 gene, as well as patients with a predominance of granular osmiophilic deposits in the lysosomal storage material, deficienc y of palmitoyl-protein thioesterase, and mutations in the CLN1 gene. We hav e divided the probands into two categories: typical (or classic) and atypic al. Most of the typical and atypical probands had onset of symptoms about o r after 4 years of age. Interfamiliar and intrafamiliar variations were fou nd, especially in the speed of becoming practically blind. Thus, our study indicates that some mutations in the CLN1, CLN2, and CLN3 genes may be asso ciated with late onset of the disease process, may have a more benign clini cal course, and clinic overlap with other forms of neuronal ceroid lipofusc inosis. (C) 1999 Academic Press.