CHILDHOOD ATAXIA WITH DIFFUSE CENTRAL-NERVOUS-SYSTEM HYPOMYELINATION

A significant number of patients with progressive leukodystrophy do no t have a definitive diagnosis. This report describes the clinical, mor phological, and biochemical characteristics of 4 unrelated girls with progressive ataxic diplegia of unknown etiology. These patients had no rmal development until the ages of 1.5 to 5 years. A diffuse confluent abnormality of the white matter of the central nervous system was pre sent on computed tomography and magnetic resonance scans obtained earl y in the course of the illness. Dementia was not present and periphera l nerves were normal. All patients were evaluated for known metabolic and degenerative diseases and no abnormalities were observed. Light an d electron microscopy of open-brain biopsy specimens from 2 girls show ed selective white matter abnormalities including hypomyelination, dem yelination, and gliosis. Myelin-specific proteins in the subcortical w hite matter were examined immunocytochemically and by Western blot ana lysis. They were of normal molecular size but were markedly reduced in quantity in both patients compared to control subjects. Lipid analysi s revealed decreased levels of characteristic myelin lipids. When exam ined by magnetic resonance spectroscopic imaging, all patients showed a marked decrease of N-acetylaspartic acid, choline, and creatine in w hite matter only. The magnetic resonance spectroscopic imaging profile is a unique diagnostic feature of this clinicopathological syndrome.