Juvenile neuronal ceroid lipofuscinosis diagnosed by skin biopsy

Abstract

Neuronal ceroid lipofuscinosis (NCL) is a group of progressive and fatal neurodegenerative disorders occurring in infancy and occasionally in adulthood, which was characterized by the accumulation of pathological lipopigments in neurons and other cells. NCL-lipopigments showed various morphological features in different subtypes of NCL, in which fingerprint profiles appeared predominantly in juvenile and adult forms of NCL.Objectives To diagnose juvenile NCL by the skin biopsy in China, and to explore morphological characters of the fingerprint pattern in extraneuronal tissues. Methods According to the history, symptoms, signs, radiological and electroencephalographic findings in a boy, NCL was clinically speculated first, and was further confirmed with light- and electromicroscopic examinations of muscle and skin biopsies on the left upper arm. Results A 9-year-6-month old boy showed visual impairment at the age of 6 years. One year later he developed seizures and progressive cognitive decline. Electroencephalogram was abnormal with epileptiform discharges. CT examination did not show remarkable change at the early stage of the disease. Two and half years later CT showed general cerebral and cerebellar atrophy and MRI showed diffuse cerebral and cerebellar atrophy with mild high signals in paraventricular area on T2 weighted scans. Routine light microscopic examination showed unremarkable change in both skin and muscle biopsy specimens. Electromicroscopic study revealed numerous lipopigments with fingerprint profiles in epithelial cells of eccrine sweat gland, but not in duct cells of eccrine sweat gland, epidermal cells, nerve fascicles, fibroblasts, vascular elements and skeletal muscle. Fingerprint profiles showed various forms: (1) combined fingerprint and curvilinear profiles in vacuoles, (2) small fingerprint profiles without vacuolation and (3) membrane bounded fingerprint profiles with granular matrix. Conclusions The radiological features of general brain atrophy and typical clinical symptoms indicated a possibility of NCL. The skin biopsy is a cost-effective tool in diagnosis of juvenile NCL. Pathological lipopigments with fingerprint profiles presented with various morphological features and selectively appeared in epithelial cells of eccrine sweat gland, but not in noneccrine sweat gland cells. Key words: Neuronal ceroid lipofuscinosis; Dermatoglyphics; Biopsy