Pyruvate Dehydrogenase Complex Deficiencies

摘要: Pyruvate dehydrogenase complex (PDC) deficiencies, affecting a critical step in carbohydrate oxidative metabolism, have heterogeneous genetic causes and outcomes. There are few correlations between numerous mutations, at least 10 genes, measured PDC enzyme activity, the clinical outcome. The presentation varies by age sex. Symptoms may include lactic acidosis, frequently severe neonates, neurological manifestations, which developmental delay/intellectual disability, hypotonia, hypertonia, dystonia, seizures, ataxia, axonal neuropathy. Neuroimaging reveals grey white matter abnormalities, including ventriculomegaly, abnormalities of corpus callosum, and/or Leigh syndrome. Defects that not specific to more likely additional systemic features. Mortality is greater males, diminishes after early childhood. Biochemical, immunohistochemical, testing be necessary suggest or confirm diagnosis. Treatment options use ketogenic diets, thiamine supplementation, and, less commonly, dichloroacetate, for case reports variable benefits. Gene therapy remains potential future treatment deficiency.