THIAMINE-RESPONSIVE LACTIC ACIDEMIA - ROLE OF PYRUVATE-DEHYDROGENASE COMPLEX

Lactic acidaemia is sometimes associated with a defect of the pyruvate dehydrogenase complex (PDHC), catalysing the thiamine-dependent decar boxylation of pyruvate. The activity of PDHC for different thiamine py rophosphate (TPP) concentrations was determined in 13 patients with la ctic acidaemia, clinically responsive to thiamine treatment in order t o assess the role of PDHC in the aetiology of thiamine-responsive lact ic acidaemia. Culture of lymphoblastoid cells and skin fibroblasts and muscle biopsies were performed in these 13 patients. The activity of PDHC to sodium dichloroacetate (DCA), known as the activator of PDHC, was also examined. Three groups were identified according to PDHC acti vity. Group 1 (two patients) displayed very low PDHC activity, which w as not increased by DCA. This PDHC activity increased at high TPP conc entrations. Group 2 (five patients) displayed below normal PDHC activi ty at low TPP concentrations, increased by DCA. This PDHC activity bec ame normal at high TPP concentrations. PDHC deficiency in these patien ts of groups 1 and 2 was due to a decreased affinity of PDHC for TPP. Group 3 included six patients with normal PDHC activity at low as well as high TPP concentrations. This PDHC activity was increased by DCA. Conclusion High concentrations of TPP may be required for maximal acti vity of PDHC in some patients with lactic acidaemia. The assay of PDHC activity, performed at a low concentration of TPP (1 x 10(-4) mM) all ows selection of patients with thiamine-responsive lactic acidaemia.