A 5-month-old infant who has been experiencing lethargy, recurrent vomiting, respiratory distress, and muscular hypotonia is brought to the emergency room near-comatose. Lab results indicate severe metabolic ketoacidosis associated with an extreme accumulation of methylmalonic acid in the blood and urine. Negative findings for pernicious anemia or other hematologic or neurologic symptoms of cobalamin deficiency indicate that the infant is suffering a defect in which of the following enzymes?

Question

Quizplus · Accepted Answer

The symptoms and lab findings are indicative of methylmalonic acidemia, which is caused by a defect in the enzyme methylmalonyl-CoA mutase. This enzyme is responsible for converting methylmalonyl-CoA to succinyl-CoA, and its deficiency leads to the accumulation of methylmalonic acid.  TCA cycle-mediated oxidation of propionyl-CoA, derived from the b-oxidation of fatty acids with an odd number of carbon atoms or from catabolism of several amino acids (eg, valine and isoleucine), requires that it first be converted to succinyl-CoA. Methylmalonyl-CoA mutase is the terminal enzyme in this conversion process. The most common physical symptoms seen in patients with defective methylmalonyl-CoA mutase activity are failure to thrive, lethargy, vomiting, muscular hypotonia, and respiratory distress. Characteristic laboratory findings will be methylmalonic acidemia.

A 5-Month-Old Infant Who Has Been Experiencing Lethargy, Recurrent Vomiting