PMID- 37673299 OWN - NLM STAT- Publisher LR - 20231006 IS - 1878-0849 (Electronic) IS - 1769-7212 (Linking) VI - 66 IP - 10 DP - 2023 Oct TI - Characteristics, differential diagnosis, individualized treatment, and prevention of hyperhomocysteinemia in newborns. PG - 104836 LID - S1769-7212(23)00142-8 [pii] LID - 10.1016/j.ejmg.2023.104836 [doi] AB - 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. CI - Copyright (c) 2023 Elsevier Masson SAS. All rights reserved. FAU - Li, Yu-Yu AU - Li YY AD - Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. FAU - Xu, Jia AU - Xu J AD - Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. FAU - Sun, Xue-Cheng AU - Sun XC AD - Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. FAU - Li, Hong-Yu AU - Li HY AD - Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. FAU - Mu, Kai AU - Mu K AD - Department of Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, China. Electronic address: 1595616561@dingtalk.com. LA - eng PT - Journal Article DEP - 20230904 PL - Netherlands TA - Eur J Med Genet JT - European journal of medical genetics JID - 101247089 SB - IM OTO - NOTNLM OT - Differential diagnosis OT - Gene variation OT - Homocysteine OT - Hyperhomocysteinemia OT - Newborn screening COIS- Declaration of competing interest Authors state no conflict of interest. EDAT- 2023/09/07 00:41 MHDA- 2023/09/07 00:41 CRDT- 2023/09/06 19:25 PHST- 2023/02/10 00:00 [received] PHST- 2023/04/21 00:00 [revised] PHST- 2023/09/02 00:00 [accepted] PHST- 2023/09/07 00:41 [pubmed] PHST- 2023/09/07 00:41 [medline] PHST- 2023/09/06 19:25 [entrez] AID - S1769-7212(23)00142-8 [pii] AID - 10.1016/j.ejmg.2023.104836 [doi] PST - ppublish SO - Eur J Med Genet. 2023 Oct;66(10):104836. doi: 10.1016/j.ejmg.2023.104836. Epub 2023 Sep 4.