| Popis: |
The study of human PDHc deficiency has shown that defects in the E1 component are most common, with a small number of E3, E2 and X defects. We report here the clinical, enzymatic, and immune mapping studies of the PDH complex in a girl presenting a primary defect in the X component. The patient, a girl born from non-consanguineous parents, presented with severe neonatal severe neonatal lactic acidosis, minor facial dysmorphia, and total corpus callosum agenesia. The metabolic profile especially revealed major hyperlactatemia, hyperpyruvicemia, and normal lactate/pyruvate ratio, without ketosis or hyperammonemia. At the present time, the girl is 4 years old and presents with relatively poor growth, minor psychomotor delay, absence of peripheral neuropathy and strabism. The activity of total PDHc in cultured skin fibroblasts and in fresh mononuclear cells is markedly decreased by about 80% as compared to the controls. The defect was not due to a PDH phosphatase deficiency since basal PDH activity in mononuclear cells could be activated by about 7 times in the presence of phosphatase activators. Immunochemical analysis with anti PDHc and anti X component antibodies demonstrates a defective X component in fibroblast mitochondria, while the other subunits of PDHc appear normal. Moreover, the complete coding region of the PDH E1alpha gene is normal, as judged by a single strand conformation polymorphism analysis. This case report suggests that the most typical phenotypes of PDHc deficiency could not only result from E1_ defect but also from X component deficiency. |
