Novel mutation of methylmalonyl-CoA mutase gene in a Thai infant with methylmalonic acidemia (mut0).

ABSTRACT

Isolated methylmalonic acidemia is found in patients with mutations in the MUT gene causing partial methylmalonyl CoA mutase deficiency, mut-, or complete methylmalonyl CoA mutase deficiency, mut0. Most mut0 patients have an earlier and more severe presentation than the other groups such as mut- and cbl defect. We report a 6-month-old Thai male presenting with wide-anion gap metabolic acidosis after acute lower respiratory infection. Urine organic acids analysis demonstrated excretions of methylmalonic acid and methylcitrate, consistent with methylmalonic acidemia. He was then started on low protein diet with an appropriate metabolic formula, L-carnitine (100 mg/kg/day), and oral vitamin B12 (1 mg/day). He had only one single metabolic episode at 2 years of age. At present, he is doing well with normal growth and development. His methylmalonyl-CoA mutase activity was undetectable compatible with mut0. He was found to be homozygous for a novel IVS11-2A>G mutation causing two aberrantly spliced transcripts. The identified mutation and enzyme activity of this patient should cause severe phenotype, although, our patient has milder clinical manifestations. Therefore we hypothesize that there are other factors that may determine the clinical phenotype of mutase deficiency in the present case.