Pathology of olivopontocerebellar atrophy with glutamate dehydrogenase deficiency

Abstract

We report the neuropathologic findings in the first patient with recognized glutamate dehydrogenase (GDH) deficiency to come to postmortem examination. He had progressive cerebellar ataxia beginning at age 21. He died at age 47 of pulmonary emboli. Postmortem examination revealed pancerebellar, olivary, and mild pontine atrophy, demyelination of the posterior columns, degeneration of anterior horn and dorsal root ganglion cells, and reduction of myelinated fibers in the sural nerve. In addition, there was neuronal storage of lipopigment diffusely throughout the CNS and the autonomic neurons, with cell distention, atrophy, and loss in selected areas.

Abnormalities of mitochondrial enzymes in hereditary ataxias

“…Partial deficiency of glutamate dehydrogenase has been reported previously in patients with dominant and non-dominant types of OPCA (8,9,14,16,17,19,20,21) FA (12) and other multiple system atrophies (18,22). Deficiencies of PDHC activity or of one of its components have been reported in fibroblasts, platelets and leukocytes from some patients with FA (5-8, lo), but normal activities have been observed in other studies in patients with hereditary ataxias (23-28).…”

“…In the last 10 years a number of mitochondrial abnormalities have been reported in subjects affected by different forms of hereditary ataxias. In particular in patients affected by Friedreich's ataxia (FA) these abnormalities include decreased overall mitochondrial oxidative metabolism (4), decreased activity of the pyruvate dehydrogenase complex (PDHC), (5-10, 20) decreased activity of valine dehydrogenase (VDH) (ll), of the mitochondrial malic enzyme (13, 14) and of glutamate dehydrogenase (GDH)/ (15). Recent studies have also provided evidence of abnormalities of the glutamate dehydrogenase (GDH) in some pa- Progressive tients affected by different types of olivopontocerebellar atrophies (OPCA) and other multiple system atrophies (16-22).…”

Glutamate metabolism of leukocytes and skin fibroblasts in spinocerebellar degeneration with lowered glutamate dehydrogenase activity

“…Patients with deficiency of vitamine E, which is one of the most important antoxidants in a living body, has been described to show clinical manifestations of SCD (23). Interestingly, neuronal storage of lipofuscin, which may be a reflection of peroxidative damage, has been reported as being diffusely present throughout the CNS in patients with GDH deficiency (24). Our result suggest that degeneration of GDH-deficient cell by L-glutamate could be related to the impaired glutamate and glutathione metabolism.…”

Glutamate dehydrogenase and aspartate aminotransferase in leukocytes of patients with motor neuron disease

“…9 We have studied 24 patients and compared the results of GDH and total aspartate aminotransferase (AAT) leukocyte activities with those in 20 matched control subjects. The cause of this disease is unknown.s Pathologic lesions are characterized by degeneration of anterior horn cells of the spinal cord and giant Betz cells and other pyramidal cells of the motor cortex.…”