Pyruvate dehydrogenase complex abnormalities

Thiamine deficiency causes decreased pyruvate oxidation, leading to accumulation of pyruvate and lactate, particularly in the blood and brain, and is accompanied by impairment of the cardiovascular, nervous, and gastrointestinal systems (Chapter 38). Inherited deficiency of pyruvate dehydrogenase complex is accompanied by lactic acidemia and abnormalities of the nervous system (e.g., ataxia and psychomotor retardation). Pyruvate carboxylase deficiency causes similar abnormalities (Chapter 15). Both inherited disorders of pyruvate utilization are autosomal recessive. 

Nervous system abnormalities may be attributed in part to diminished synthesis of neurotransmitters rather than to inadequate synthesis of ATP. In pyruvate dehydrogenase complex deficiency, diminished levels of acetyl-CoA cause decreased production of acetylcholine in pyruvate carboxylase deficiency, decreased production of... 

Kuroda, Y., Kline, J.J., Sweetman, L., Nyhan, W.L. and Groshong, T.D. (1979), Abnormal pyruvate and a-ketoglutarate dehydrogenase complexes in a patient with lactic acidemia. Pediatr. Res., 13,928. 

---