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

Prenat Diagn. 2019 Oct;39(11):993-997. doi: 10.1002/pd.5519. Epub 2019 Aug 5.

Abstract

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.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Amino Acid Metabolism, Inborn Errors / genetics
  • Amniocentesis
  • Amniotic Fluid / chemistry*
  • Amniotic Fluid / cytology
  • Biomarkers / analysis*
  • Female
  • Genetic Testing
  • Humans
  • Methylmalonyl-CoA Mutase / genetics
  • Oxidoreductases / genetics
  • Pregnancy
  • Retrospective Studies

Substances

  • Biomarkers
  • MMACHC protein, human
  • Oxidoreductases
  • Methylmalonyl-CoA Mutase

Supplementary concepts

  • Methylmalonic acidemia