Dysautonomia in an infant with secondary hyperammonemia due to propionyl coenzyme A carboxylase deficiency

A male infant who had vomiting and coma in the absence of ketoacidosis was initially thought to have dysautonomia because of abnormal responses to methacholine and histamine, as well as abnormal urinary catecholamine excretion. Following an episode of hyperammonemia, a liver biopsy was performed which revealed a partial deficiency of carbamyl phosphate synthetase activity. The patient was treated with a protein-restricted diet supplemented with a mixture of ketoacid analogues of the essential amino acids, which precipitated ketosis and acidosis. A primary deficiency of propionyl coenzyme A (CoA) carboxylase was subsequently demonstrated. Because disorders of propionate metabolism may not initially present with ketoacidosis, we recommend examination of both plasma and urine for metabolites of this pathway, as well as direct measurement of propionyl CoA carboxylase activity in peripheral blood leukocytes, before performing a liver biopsy to evaluate urea cycle enzyme activities, and particularly before adding keto acid/amino acid mixtures to a protein-restricted diet.