neurogenetic of neuronal ceroid lipofucinosis (ncl)

ncls, which are some of the most common degenerative disorders, often also cause progressive blindness. the diagnosis is suggested by characteristic inclusions, visible by electron microscope, in a skin or conjunctival biopsy specimen. during the last several years, the biochemical and genetic basis of the ncls has been elucidated. the ncls are characterized by the accumulation of autofluorescent neuronal storage material within neuronal lysosomes, leading to neuronal death and cerebral atrophy. traditionally, various types of ncls were differentiated according to the age at which neurologic symptoms first became evident and the ultrastructural morphology of the inclusions. this classification has now been supplemented by genetic analysis. the major subtypes are the infantile form, first reported from finland in 1973 by santavuori and her associates, (the late infantile form was first described by jansky in 1909 and subsequently by bielschowsky and batten), the juvenile form described by spielmeyer, and the adult form first described by kufs. at least four other disease gene loci have been mapped, bringing the current total number of ncls to nine subtypes. all are transmitted in an autosomal recessive manner. in addition, an autosomal dominant form of ncl has been delineated and is one cause for early onset of dementia .the relative frequencies of autosomal recessive forms in the clinical and pathologic series of wisniewski and colleagues are as follows: infantile ncl: 11.3%, late infantile ncl (lincl): 36.3%, juvenile ncl: 51.1%, and adult ncl: 1.3%. in this review, we will introduce these variants and their diagnostic approaches.