Excretion pattern of branched-chain amino acid metabolites during the course of acute infections in a patient with methylmalonic acidaemia

Abstract

A 1-year-old boy with a typical B₁₂-responsive form of methylmalonic acidaemia was hospitalized twice due to acute bacterial infections. On both occasions, the child was lethargic with a severe ketoacidosis on admission. Intensive therapy with protein restriction, intravenous administration of electrolytes and antibiotics was effective within 4 days on both occasions. The urinary excretion of organic acids showed the same pattern on both occasions. There were rising excretion concentrations, reaching a peak value within the first 24-hour period, for the following compounds: 3-hydroxybutyric acid, 3-hydroxypropionic acid, 3-hydroxyisobutyric acid and 3-hydroxyisovaleric acid. Excretion concentrations of the following rose for 48 h: isobutyric acid, 2-methylbutyric acid, isovaleric acid, lactic acid and the 2-oxo-acids.

There was no increase until 12–24 h after the onset of severe illness in the excretion of propionic acid and methylmalonic acid. Propionic acid excretion was maximal at about 48 h, while peak excretion of methylmalonic acid was delayed until about 72 h after the onset of severe illness; at this time there was clinical improvement. The biochemical implications of this excretion pattern are discussed.