Experience with Prenatal Diagnosis of Propionic Acidaemia and Methylmalonic Aciduria

The prenatal diagnosis of disorders of organic acid metabolism by enzymology on cultured amniotic cells obtained by amniocentesis at 15-18 weeks’ gestation has been applied to an increasing number of these disorders during the past 10 years, including propionic acidaemia and methylmalonic aciduria (see e.g. Chalmers and Lawson, 1982; Sweetman et al., 1982). The prenatal diagnosis of the latter two metabolically-related disorders is now carried out routinely by measurement of incorporation of label from [l-14C]propionate into cell protein in cultured cells or, more rarely, by direct measurement of activity of propionyl-CoA carboxylase (EC 6.4.1.3) or methylmalonyl-CoA metabolism. Methods involving cell culture are time-consuming because of the requirement for sufficient cells for assay and potentially unreliable because of the possibility of failed cultures and the rare occurrence of overgrowth by maternal fibroblasts (Buchanan et al., 1980). The direct chemical analysis of cell-free amniotic fluid for metabolites excreted by the fetus offers the considerable advantages of rapid and early diagnoses and repeatable and reliable assays (see, e.g. Chalmers and Lawson, 1982). Propionic acidaemia and methylmalonic aciduria can be diagnosed in this way by measurement of methylcitrate or of methylmalonate and methyldtrate respectively. We report here our experience of monitoring 12 pregnancies at risk for these diseases using a combination of enzymology and direct chemical methods. Ambiguous results in one pregnancy at risk for propionic acidaemia necessitated enzymology of fetal leucocytes to resolve the diagnosis.