The neurologic symptomatology in 22 patients with Niemann-Pick disease type C have been analyzed and reported from the Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
The neurologic symptomatology in 22 patients with Niemann-Pick disease type C have been analyzed and reported from the Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD. Three phenotypes are described: 1) an early onset, rapidly progressive form associated with severe hepatic dysfunction and psychomotor delay during infancy and later with supranuclear vertical gaze paresis, ataxia, spasticity, and dementia; 2) a delayed onset, slowly progressive form beginning in early childhood with mild intellectual impairment, supranuclear vertical gaze paresis and ataxia, and later associated with dementia, seizures and extrapyramidal deficits; 3) a late onset slowly progressive form beginning in adolescence or adulthood. The classic supranuclear disorder of gaze, initially and predominantly affecting vertical eye movements, is nearly pathognomonic for NPC. The biochemical disorder is a marked deficiency in the ability of cultured fibroblasts to esterify exogenously supplied cholesterol. This deficiency may be assayed in confirmation of the diagnosis when presentation is atypical. [
COMMENT. Mild intellectual impairment presenting as poor school performance was the most common initial neurologic abnormality. Additional presenting signs included ataxia, dysarthria, and impaired vertical gaze. Within three years of the initial deficit most of the patients had cognitive impairment, abnormal vertical gaze and ataxia. Saccadic paresis was manifested by a complaint of difficulty in reading or in descending stairs. Hepatosplenomegaly was first noted at varying ages from birth to 24 years with a mean age of six years. It preceded neurological abnormalities in one-half the patients and was found only in the early onset rapidly progressive group.