Treatment of chronic congenital lactic acidosis by oral administration of dichloroacetate.

Sodium dichloroacetate (DCA) was administered orally at a dose of 50 mg per kg body weight twice or three times per day to a newborn infant with lactic acidosis of unknown cause (patient 1) and to a 15-year-old boy with mitochondrial encephalomyopathy associated with lactic acidosis (patient 2). In patient 1, during treatment with DCA, DCA accumulated in the blood judging from the findings that the urinary excretion of DCA increased cumulatively and the blood lactate level rapidly decreased to the normal range. In patient 2, the blood DCA level gradually increased during treatment to a concentration of 250 micrograms ml-1 and the blood lactate level decreased and was maintained within the normal range. DCA was detected in the brain (25 micrograms g tissue-1) and the liver, kidney and muscle (33.8, 33.8 and 26.3 micrograms g tissue-1, respectively) obtained at autopsy of patient 1, and in the cerebrospinal fluid of patient 2 at a concentration of 125 micrograms ml-1 when the blood concentration was 250 micrograms ml-1. The lactate levels in the cerebrospinal fluid decreased from 7 and 4 mmol l-1 to 2.4 and 2.6 mmol l-1 in patients 1 and 2, respectively. Thus DCA may be useful in clinical treatment of chronic congenital lactic acidosis because it seems to cross the blood-brain barrier. However, it must be given at non-toxic doses, determined by monitoring the concentrations of lactate and DCA in the blood, because orally administered DCA tends to accumulate in tissues.