International Journal of Neonatal Screening (Jul 2021)

Pilot Study on Neonatal Screening for Methylmalonic Acidemia Caused by Defects in the Adenosylcobalamin Synthesis Pathway and Homocystinuria Caused by Defects in Homocysteine Remethylation

  • Reiko Kagawa,
  • Go Tajima,
  • Takako Maeda,
  • Fumiaki Sakura,
  • Akari Nakamura-Utsunomiya,
  • Keiichi Hara,
  • Yutaka Nishimura,
  • Miori Yuasa,
  • Yosuke Shigematsu,
  • Hiromi Tanaka,
  • Saki Fujihara,
  • Chiyoko Yoshii,
  • Satoshi Okada

DOI
https://doi.org/10.3390/ijns7030039
Journal volume & issue
Vol. 7, no. 3
p. 39

Abstract

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Neonatal screening (NS) for methylmalonic acidemia uses propionylcarnitine (C3) as a primary index, which is insufficiently sensitive at detecting methylmalonic acidemia caused by defects in the adenosylcobalamin synthesis pathway. Moreover, homocystinuria from cystathionine β-synthase deficiency is screened by detecting hypermethioninemia, but methionine levels decrease in homocystinuria caused by defects in homocysteine remethylation. To establish NS detection of methylmalonic acidemia and homocystinuria of these subtypes, we evaluated the utility of indices (1) C3 ≥ 3.6 μmol/L and C3/acetylcarnitine (C2) ≥ 0.23, (2) C3/methionine ≥ 0.25, and (3) methionine 12 deficiency during NS. Methylene tetrahydrofolate reductase deficiency was confirmed for the case identified by index 3, which was examined because an elder sibling was affected by the same disease. Based on these data, a prospective NS study is underway.

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