USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

Which enzyme deficiency leads to increased urine levels of methylmalonic acid and propionic acid along with symptoms such as hyperammonemia, ketotic hypoglycemia, and metabolic acidosis?

1. Methylmalonyl-CoA mutase

2. Glucose-6-Phosphatase

3. Pyruvate Carboxylase

4. Adenosine Deaminase

The correct answer is: Methylmalonyl-CoA mutase

The correct choice is associated with a deficiency in methylmalonyl-CoA mutase, an enzyme involved in the metabolism of certain amino acids and fatty acids, specifically in the conversion of methylmalonyl-CoA to succinyl-CoA. When this enzyme is deficient, there is a buildup of methylmalonic acid, which subsequently leads to increased levels of propionic acid as well. This metabolic disruption manifests clinically as hyperammonemia (because of impaired urea cycle function), ketotic hypoglycemia (due to the body's inability to properly utilize fats for energy and produce ketone bodies), and metabolic acidosis (resulting from the accumulation of acids in the body). In this scenario, the urine levels of both methylmalonic acid and propionic acid serve as diagnostic markers. Elevated levels of these organic acids in urine indicate a problem with the metabolism of certain dietary components, typically seen in conditions like methylmalonic acidemia, which is often caused by a deficiency in methylmalonyl-CoA mutase. The other enzymatic deficiencies listed do not lead to the same combination of metabolic derangements. For example, glucose-6-phosphatase deficiency primarily leads to glycogen storage diseases such as von Gierke's disease