2-KETOGLUTARATE DEHYDROGENASE-DEFICIENCY, A RARE CAUSE OF PRIMARY HYPERLACTATEMIA - REPORT OF A NEW CASE

Two new familial cases of 2-ketoglutarate dehydrogenase (2-KGD) defici ency are reported: a girl who died at 10 years and a boy, still alive at 4 years, born to consanguineous parents. The cases developed progre ssively severe encephalopathy with axial hypotonia, psychotic behaviou r, pyramidal symptoms and failure to thrive. Both children exhibited p ermanent lactic acidosis with acute episodes during emotional stress a nd various infections, associated with elevated lactate/pyruvate (L/P) ratio and slightly decreased ketone body ratio in plasma. In fibrobla sts, the L/P ratio was greatly increased in the boy. No respiratory ch ain complex deficiency could be demonstrated in cultured fibroblasts o r in mitochondria isolated from a muscle biopsy performed on the boy. In muscle isolated mitochondria, a progressive decrease of the rate of glutamate oxidation was observed after ADP addition; the rate of 2-ke toglutarate oxidation was low in the absence of ADP and did not increa se after ADP addition. 2-KGD deficiency was demonstrated in fibroblast s from both children and in the boy's muscle and myoblasts. The 2-KGD complex is composed of three separate enzymes: E1, E2 and E3. We could demonstrate in our patient that the E1 and E3 subunits were normal, s uggesting that the E2 component could be responsible for the defect.