We describe the successful use of
sodium benzoate in a neonate with
hyperammonemia associated with congenital
lactic acidosis caused by a partial deficiency of the E1 component of
pyruvate dehydrogenase (PDH); of note, this biochemical disturbance has not been previously described in
PDH deficiency. The
pyruvate dehydrogenase complex in skin fibroblasts had 48% of normal activity with a deficiency of the E1 component. The infant presented with rapid onset of a severe metabolic
lactic acidosis,
hyperventilation,
hyperammonemia, and
coma. At 30 hours of age continuous
peritoneal dialysis was started; however, plasma NH3 concentrations remained in the 300-400 micrograms/dl range over the next 12 hours.
Sodium benzoate, 250 mg/kg, was infused intravenously with a decrease in plasma
ammonia of 25 micrograms/dl/hr.
Hippurate was documented in the urine and peritoneal fluid after
benzoate therapy. At 10.5 months of age, 50 mg/kg dichloroacetate was administered orally under fasting conditions, which resulted in a 56 and 62% reduction in the serum
lactate and
pyruvate levels, respectively; after 2 weeks on dichloroacetate his fasting levels were significantly decreased. Fibroblast PDH activity responded similarly to this
drug. In our patient
sodium benzoate was rapidly effective in producing a decline in plasma
ammonia that was associated with clinical improvement. We feel that its use in organic acidemias deserves further evaluation and, furthermore, that any child with suspected
PDH deficiency requires a clinical trial of dichloroacetate.