Clinical Reasoning: A young man with progressive subcortical lesions and optic nerve atrophy

Abstract

The male patient is the third child of unrelated Japanese parents. His older sister had tachypnea and feeding difficulties, and died at 5 days of age. The patient was delivered at term (birthweight, 3.8 kg), following an unremarkable pregnancy. He presented with tachypnea, metabolic acidosis, and hyperammonemia (944 μmol · L−1) at 6 days. ### Questions for consideration: 1. What is the differential for infantile presentation of hyperammonemia in the neonatal period? 2. What laboratory tests would you pursue? GO TO SECTION 2 Hyperammonemia occurs in urea cycle disorders (e.g., ornithine transcarbamylase deficiency) and organic acidurias (e.g., methylmalonic aciduria, propionic aciduria, and isovaleric aciduria) and fatty acid oxidation defects (e.g., multiple acyl-CoA dehydrogenase deficiency). The existence of acidosis with ketosis indicates organic aciduria, whereas respiratory alkalosis is observed in urea cycle defects. Diagnosis is based on quantitative assay of amino acids and acylcarnitines from dried blood and organic acids in urine samples. ### Case: part 2. Elevated levels of 2-methylcitric acid and 3-hydroxypropionic acid were found in the urine. The plasma propionic acid concentration was increased (4.5 mg · dL−1), and propionyl-CoA …