Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns

Yu-Yu Li; Jia Xu; Xue-Cheng Sun; Hong-Yu Li; Kai Mu

doi:10.1016/j.ejmg.2023.104836

Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns

Eur J Med Genet. 2023 Oct;66(10):104836. doi: 10.1016/j.ejmg.2023.104836. Epub 2023 Sep 4.

Authors

Yu-Yu Li¹, Jia Xu¹, Xue-Cheng Sun¹, Hong-Yu Li¹, Kai Mu²

Affiliations

¹ Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China.
² Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. Electronic address: 1595616561@dingtalk.com.

PMID: 37673299
DOI: 10.1016/j.ejmg.2023.104836

Abstract

Objectives: This study aimed to investigate the incidence rate, clinical phenotype, gene variation spectrum, and prognosis of neonatal hyperhomocysteinemia (HHcy) and explore its diagnosis, individualised treatment, and prevention strategies.

Methods: We screened 84722 neonates for HHcy using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with biochemical detection, urine gas chromatography-mass spectrometry (GC-MS), and next-generation sequencing (NGS) for gene analysis to comprehensively differentiate and diagnose diseases.

Results: 18 children (P1-P18) were diagnosed with methylmalonic acidemia (MMA) and HHcy, and fourteen known and one new variant of the MMACHC gene were found. Five children showed poor mental reactions, brain dysplasia, lethargy, hyperbilirubinemia, and jaundice, whereas the other 13 children had no evident abnormalities. These children were all cobalamin- and folic acid-reactive types, and they were mainly supplemented with cobalamin, L-carnitine, betaine, and folic acid. The mother of P12 had a prenatal diagnosis at the next pregnancy; the results showed that MMACHC gene was not pathogenic and she gave birth to a healthy baby. One child (P19) was diagnosed with methylenetetrahydrofolate reductase (MTHFR) deficiency, and one new mutation was detected in the MTHFR gene. Patient P19 showed congenital brain dysplasia, neonatal anaemia, and hyperbilirubinemia, and treatment consisted mainly of betaine and cobalamin supplementation. One child (P20) was confirmed to have methionine adenosyltransferase I (MAT I) deficiency but had no clinical manifestations. After treatment, all the children had a good prognosis.

Conclusion: The incidence of neonatal HHcy in the Zibo area was 1/4236, and the common pathogenic variants were c.609G>A, c.80A>G, and c.482G>A in the MMACHC gene. Patients with HHcy can achieve a good prognosis if pathogenic factors and targeted treatment are identified. Gene analysis and prenatal diagnosis contribute to the early prevention of HHcy.

Keywords: Differential diagnosis; Gene variation; Homocysteine; Hyperhomocysteinemia; Newborn screening.