Lactic acidaemia.
Congenital childhood lactic acidaemia is a poorly understood group of genetic diseases. The most common underlying inherited defect encountered in this group is deficiency of the pyruvate dehydrogenase complex. Of 23 cases we have diagnosed, 18 have a deficiency in the first component of the complex, the E1 decarboxylase, while the other five have multiple alpha-keto acid dehydrogenase deficiency due to a defect in lipoamide dehydrogenase. In addition to the lactic acidosis associated with pyruvate decarboxylase deficiency, ten of the cases showed evidence of facial dysmorphism consisting of a narrow head, wide nasal bridge and flared nostrils or gross microcephaly. Two further patients had agenesis of the corpus callosum. Isolated pyruvate carboxylase deficiency was found to present in two different forms, one with lactic acidaemia and mental retardation, the other with lactic acidaemia, hyperammonaemia citrullinaemia and hyperlysinaemia. The former presentation we have shown to be associated with the presence of a biotinylated pyruvate carboxylase protein of the correct subunit molecular weight (125 kd) which has no catalytic activity (CRM + ve). The latter we have shown to be associated with the absence of any recognizable pyruvate carboxylase protein (CRM - ve).
D000015:Abnormalities, Multiple / Q000209:etiology; D002648:Child; D006801:Humans; D007773:Lactates / Q000097:blood*; D019344:Lactic Acid; D008661:Metabolism, Inborn Errors / Q000209:etiology / Q000378:metabolism*; D015324:Pyruvate Carboxylase Deficiency Disease; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid
D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid