Long term use of low-doses of dichlo-roacetate in a child with congenital lactic acidosis: 4

Abstract

Dichloroacetate(DCA) has been shown to reduce plasma lactate levels in healthy and diabetic adults as well as in a child with congenital lactate acidosis(CLA).(F.Coude et al.New Engl.J.Med. 299: 1365, 1978).In a 12 year-old boy with CLA, DCA was administered orally during 12 months. The underlying biochemical defect in this patient is still unkown. In cultured fibroblasts, enzymatic activities of pyruvate dehydrogenase(PDH), pyruvate carboxylase, phosphoenolpyruvate carboxykinase were within the normal range. DCA therapy given at a dose as low as 15 mg/kg b.d. every second day, was effective in lowering plasma lactate (7.6 mMol. to 0.9 mMol). In addition growth rate was stimulated (7 cm/year). Routine serial analysis were made throughout the study including blood levels of glucose, lipids, ketones, uric acid, oxalic aciduria, and the search of renal, hepatic, ocular and neural dysfunction. No adverse physical or biological effects associated with DCA therapy were observed. However DCA was not more effective on the gradually deteriorating neurological condition of this child than previous therapeutic attempts with thiamine, biotine, lipoic acid and ketonemic diet. We conclude that the return to normal of lactate levels was probably secondary to the activation of muscular PDH; it is not clear whether the neurological disorder is related to abnormal levels of a metabolite in the plasma.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD