Prenatal diagnosis of methylmalonic aciduria from amniotic fluid using genetic and biochemical approaches.

Objectives This study reported the clinical prenatal diagnosis experience of families affected by methylmalonic acidemia (MMA) evaluated at a single prenatal diagnosis center over 8 years, and the reliability of a biochemical approach for prenatal diagnosis was analyzed. Methods Prenatal diagnosis data for 187 MMA families referred to our center from 2009 to 2016 were reviewed retrospectively. The results of the genetic analysis and biochemical approach were compared. Results A total of 41 MMA-affected pregnancies (21%) were identified. The biochemical analysis could identify the true status of 99.5% of fetuses. The diagnostic sensitivities of the propionylcarnitine (C3) level, the C3 to acetylcarnitine (C2) ratio (C3/C2), the methylmalonic acid, and methylcitrate levels in the amniotic fluid were 95.1%, 100%, 100%, and 82.9%, respectively, and the specificities were 98.7%, 99.3%, 97.4%, and 96.7%, respectively. Conclusions The biochemical analysis could be optionally used in the prenatal diagnosis of MMA, especially in cases where the genetic results are inconclusive. Among the four tested biochemical markers, C3/C2 appeared to be the most reliable.