Journal of the Neurological Sciences, 1989, 93:311-318 311 Elsevier JNS 03238 Familial intermittent ataxia due to a defect of the E 1 component of pyruvate dehydrogenase complex L.A. Bindoff 1'2, M.A. Birch-Machin t'2, L. Farnsworth 1'2, D. Gardner-Medwin ~, J.G. Lindsay 3 and D.M. Turnbull ~ ~ Division of Clinical Neuroscience, School of Neurosciences, 2Department of Pharmacological Sciences, Univer- sity of Newcastle upon Tyne (U.K.), and 3DeparOnent of Biochemistry, University of Glasgow, Glasgow (U.K.) (Received 17 May, 1989) (Revised, received 22 June, 1989) (Accepted 23 June, 1989) SUMMARY Disturbances of pyruvate metabolism have been implicated in the aetiology of several neurological disorders including Leigh's disease and familial ataxia. We have re-investigated a patient whose initial description documented intermittent ataxia, a presumed disorder of pyruvate metabolism and an X-linked pattern of inheritance. Recent studies showed he had slow oxidation of pyruvate, low pyruvate dehydro- genase complex (PDC) activity and immunochemical evidence of E1 deficiency in skeletal muscle mitochondria. This is consistent with the recent finding that the gene for EI~ is on the X chromosome. Key words: Intermittent ataxia; Pyruvate dehydrogenase complex; E~ subunit; X-linked inheritance pattern INTRODUCTION The pyruvate dehydrogenase complex (PDC) catalyses the oxidative decar- boxylation of pyruvate to acetyl-CoA. It is composed of multiple copies of 3 enzymes, pyruvate dehydrogenase (El) [EC 1.2.4.1], dihydrolipoamide transacetylase (E2) Correspondence to." Dr. D.M. Turnbull, Division of Clinical Neuroscience, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, U.K. 022-510X/89/$03.50 © 1989 Elsevier Science Publishers B.V. (Biomedical Division)