Pitfalls in the prenatal diagnosis of propionic acidemia

Prenatal diagnosis of propionic acidemia can be performed by two independent methods: measuring an elevated quantity of the metabolite methylcitrate in amniotic fluid; and demonstrating deficient activity of propionyl-CoA carboxylase in amniocytes cultured from the fluid. Discordant results in a pregnancy at risk for propionic acidemia were obtained. Elevated concentration of methylcitrate indicated an affected fetus, but the activity of propionyl-CoA carboxylase was normal. An affected female infant was born. Chromosome variant analysis demonstrated that between passage two and four overgrowth of the female fetal cells by contaminating maternal cells led to the 'false negative' results obtained by enzyme assay. This experience demonstrates the value of analysis of abnormal metabolites in amniotic fluid and highlights a problem that could confound the prenatal diagnosis of any condition assessed by enzyme activity.