Abstract
A full term neonate developed hypotonia, profound lactic acidosis (HCO3 3 mM, lactate 10mM) and persistent hyperammonemia (896μg/dl) at age 8 hr. Despite peritoneal dialysis, blood NH3 remained elevated (>200μg/dl); IV benzoate was helpful, and hippurate could be detected in the peritoneal fluid. Multiple GLC studies of urine revealed only massive quantities of lactate; urinary orotic acid was minimally elevated. Serum alanine was grossly elevated. Skin fibroblast studies: normal carboxylase enzyme levels, pyruvate dehydrogenase (PDH) 52% of control, whole cell 1−14C pyruvate oxidation 42% of control. As in the other case reports, even a partial PDH deficiency typically causes severe clinical and biochemical disturbances. At age 10 mo, 50 mg/kg oral dichloroacetate (DCA), an inhibitor of the protein kinase which curtails PDH activity, reduced serum lactate and pyruvate by 50% within 2 hr; of interest, DCA also enhanced residual fibroblast PDH activity by 10-15%. However, despite biochemical improvement the patient developed refractory ascites, respiratory failure, progressive cerebral atrophy, and died at age 12 mo.
PDH deficiency should be included in the differential diagnosis of neonatal hyperammonemia and this may be ameliorated by benzoate. DCA should be considered in the treatment of congenital lactic acidosis.
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McCormick, K., Viscardi, R. & Robinson, B. PYRUVATE DEHYDROGENASE DEFICIENCY WITH LACTIC ACIDOSIS AND HYPERAMMONEMIA: RESPONSES TO DICHLOROACETATE AND BENZOATE. Pediatr Res 18 (Suppl 4), 297 (1984). https://doi.org/10.1203/00006450-198404001-01222
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DOI: https://doi.org/10.1203/00006450-198404001-01222
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