Congenital Lactic Acidosis

Abstract

For use in screening for disorders of pyruvate metabolism in cultured skin fibroblasts, we developed a sensitive assay method for measuring the rates of decarboxylation of (1-^14 C)-pyruvate using dichloroacetate (DCA). By this method, disorders of the mechanism of activation of pyruvate dehydrogenase (PDH) were found in 2 of 10 patients with congenital lactic acidosis of unknown cause. We also found that DCA activated the PDH complex and the tricarboxylic acid cycle, which is an important pathway of energy metabolism, in the brain and other tissues, and lowered the lactate level in the blood and cerebrospinal fluid. Therefore, DCA therapy may be useful in treatment of chronic congenital lactic acidosis if this treatment is started sufficiently early.

Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy

“…Roodhoft et al [18] administered a combination of camitine, riboflavin, nicotinamide, L-va-line, L-isoleucine, and ubiquinone to a 4-month-old infant with a combined complex I and complex IV defect. Thiamine is the coenzyme for pyruvate dehydrogenase [9,10,21]. The lactate concentration was elevated before therapy in blood and CSF, no comments are available on these values after cessation of therapy.…”