Assays / Genetic Enzymes / Methylmalonic Acidaemia

This is a heterogeneous disorder in which there may be deficiency of the apo enzyme, methylmalonyl-CoA mutatse, or a defect in synthesis of the essential co-factor adenosyl cobalamin. In some of the latter patients there is homocystinaemia in addition to methylmalonic acidaemia because of defective synthesis of methylcobalamin as well as adenosyl cobalamin, the former being a co-factor for one of the reactions catalysing the remethylation of homocysteine to methionine. The most severely affected patients suffer a severe illness in the neonatal period with grunting respiration, vomiting, dehydration and drowsiness. There is metabolic acidosis and ketosis leading to coma and death. These patients have no functional mutase (mut^o). Other patients have a structurally altered mutase with reduced affinity for adenosylcobalamin (mut^-) and these children may respond to dietary protein restriction. Patients with combined methylmalonic acidaemia and homocystinaemia have a variable phenotype, and are also biochemically and genetically distinct: cells from the patients comprise three complementation groups. Symptoms include failure to thrive, poor feeding, lethargy, developmental retardation and megaloblastic anaemia.

ENZYME TEST: [14C]-propionate incorporation is measured for diagnosis of these patients. This assay is not offered for prenatal diagnosis of methylmalonic acidaemia directly on chorionic villi.

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