Coma Caused by Methylmalonic Acidemia in a Taiwanese Girl

Methylmalonic acidemia (MMA) is an inborn error of metabolism caused by an accumulation of methylmalonic acid in blood and body tissue due to severe defi ciency or a lack activity of the mitochondrial methylmelonyl-CoA mutase (MCM) enzyme. Affected individuals are typically presented during the newborn period with vomiting, failure to thrive, hyperammoninemia and ketoacidosis. Several mutations on MCM gene (MUT gene) were reported worldwide, but Taiwan. Here, we described a previously healthy 2-year-old Taiwanese girl, who had normal growth and developmental milestones, presented with abdominal pain, vomiting and was in coma. Physical examination revealed tachycardia, tachypnea and poor skin tugor. Laboratory investigations showed high anion gap (anion gap 35 mmol/L) metabolic acidosis (HCO3 - 2.7 mmol/ L), normal plasma osmolar gap (10 mosm/kgH2O), β-hydroxybutyrate (4 mmol/l), ketonuria, hypoglycemia (2.6 mmol/l), hyperammoneemia (152.9 μmol/l), normal lactic acid level, normal renal function, suggesting a clinical diagnosis of organic acidemia. Urinary analysis for organic acid showed increased excretion of methylmalonic acid and in vitro MCM enzyme activity analysis by detecting the lymphoblast revealed trivial residual activity. Molecular analysis of MCM gene revealed that she was compound heterozygous for two mutation of MUT gene, a recurrent G427D and a novel mutation F307L; these two mutations are not identified of 100 alleles for 50 unrelated normal Taiwanese. MMA should be considered as a cause of high anion gap metabolic acidosis in children, even without previous episode and normal development milestone. Molecular study is needed to make a diagnosis of MMA under the trivial residual activity of MCM enzyme.