Abstract. The authors report 2 familial cases of neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in the liver. In both cases, disorders started immediately after birth and were characterized by major neurological symptoms, acute metabolic acidosis with hyperketonemia and hyperammonemia. Course was rapidly fatal despite intensive care, bicarbonate therapy and several therapeutic attempts with biotin and thiamine. Hyperlactacidemia was associated with dramatic increase in lactate/pyruvate ratio, without anoxia, in contrast with decreased β hydroxybutyrate/acetoacetate ratio. This unusual metabolic pattern may be assumed to result from decreased oxaloacetate synthesis as a result of pyruvate carboxylase deficiency, and impairment of oxaloacetate dependent mitochondrial redox shuttles. Post mortem enzymatic study of the liver and kidney showed biotin unresponsive total deficiency of pyruvate carboxylase. Other gluconeogenic enzyme activities were normal.

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