Morphologic Diagnosis in Neuronal Ceroid Lipofuscinosis

Abstract

Morphologic pathology in NCL is marked by two processes, the interaction of which has not yet been completely clarified: 1) degeneration of nerve cells, foremost in the cerebral cortex, resulting in considerable cerebral atrophy in early childhood forms, likely responsible for clinical and neuroradiological findings; 2) widespread accumulation of auto-fluorescent lysosomal lipopigments of varying ultrastructure, the demonstration of which is still largely responsible for diagnostic recognition of an individual patient's NCL. Numerous tissues and organs are available for biopsy, among them brain (historical), rectum (still favoured by some), skeletal muscle and peripheral nerves (largely by coincidence or "mistake"), skin and conjunctiva (the latter inferior to former in diagnostic yield) and, most easily retrievable, circulating lymphocytes. The distinct ultrastructure in the circulating lymphocytes permits a close cliniconeuropathological correlation which may only be surpassed by future genetic results. Diagnostic morphology of NCL variants and adult NCL, however, is still problematic, the former concerning autopsy studies of the brain, the latter concerning extracerebral biopsies.

Key words

Neuronal ceroid lipofuscinosis - Lipopigments - Cell death - Ultrastructure - Diagnosis