A NEW FORM OF CONGENITAL LACTIC ACIDOSIS

Two siblings, 6 and 40 months of age, with a previously unrecognized form of pyruvate decaboxylase (PDC) developed lactic acidosis, hyperammonemia, and proximal renal tubular acidosis, along with persistent ketosis and severe retardation of growth and development. Urine metabolites showed consistently high lactate, pyruvate, fumarate, and succinate, the latter two unusual in most forms of congenital lactic acidosis. Ornithine transcarbmyalase was demonstrated at 50% normal activity in the one patient measured. This may partially explain the persistent hyperammonemia. Therapy with megadoses of thiamine, pyridoxine, and monosodium glutamate were without effect. Large doses of biotin caused a transient decrease in the lactic acidosis but no long term clinical effect was demonstrated. Ketogenetic diet, often advocated for treatment of lactic acidosis, resulted in clinical deterioriation. Therapy with large doses of citrate, possibly acting as a TCA cycle substrate, resulted in clinical stabilization but continued poor development. These two patients appear to represent a new variation of congenital lactic acidosis which have not responded to conventional forms of therapy.