Variant late infantile neuronal ceroid-lipofuscinosis: pathology and biochemistry.

The neuronal ceroid-lipofuscinoses (NCL) are among the most common inherited neurodegenerative disorders of childhood. The genomic defect causing a variant late infantile neuronal ceroid-lipofuscinosis (vLINCL, also called CLN-5 or variant Jansky-Bielschowsky disease) has recently been localized to chromosome 13q22, thus delineating this disease as a separate entity. This particular form of NCL is clinically well defined, but lacks pathomorphological and biochemical description. The present analyses indicate that subunit c of the mitochondrial ATP synthase is the major protein in vLINCL brain storage cytosomes. These cytosomes also contain minor amounts of sphingolipid activator proteins (SAPs). The immunohistological distribution of subunit c and SAPs in the central nervous system (CNS) and visceral tissues closely resembles that of classical LINCL. Thus, despite clinical differences and the fact that various forms of NCL are caused by different genetic defects, variant and classical LINCL as well as juvenile NCL are all characterized by pronounced lysosomal accumulation of the same hydrophobic protein, subunit c of the mitochondrial ATP synthase.