Neurological disorders associated with deficiency of glutamate dehydrogenase.

Glutamate dehydrogenase (GDH) activity was measured in leukocytes from 88 patients with various types of degenerative neurological disorders affecting primarily the cerebellum and/or the basal ganglia, and 26 healthy control subjects. Twelve patients with slowly progressive multiple-system atrophic disorders were found to have a partial deficiency of this enzyme (52% of control level). The majority of these patients evidenced a constellation of neurological findings consistent with the diagnosis of olivopontocerebellar atrophy, although others were atypical in their neurological manifestations. Thus, GDH-deficient patients were encountered with predominantly extrapyramidal manifestations (atypical Parkinson's disease), cerebellar dysfunction with peripheral neuropathy, or anterior horn cell signs, suggesting that a pleomorphic phenotypic expression of the enzymatic deficiency may occur. Seven cases of GDH deficiency were familial and 5 were sporadic. The former patient group consisted of siblings of either sex, but no parents or offspring were affected. The genetic pattern of the disorder is compatible with autosomal recessive inheritance. Patients with dominantly inherited olivopontocerebellar atrophy or other types of cerebellar or basal ganglia degenerative neurological disorders showed normal GDH activity. Leukocyte GDH was fractionated into "particulate-heat labile" and "soluble-heat stable" components. In the patients the decrease in activity was limited to the "particulate-heat labile" component. A genetic mutation of a GDH "isoenzyme" may occur in some patients with multiple-system degeneration.