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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmg.2023.104836 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dissecting the role of vitamin B metabolism in craniofacial development through analysis of clinical phenotypes and model organism discoveries.
Differentiation
December 2024
Department of Biological Sciences, University of Texas El Paso, 500 W. University Ave 79968, El Paso, TX, USA. Electronic address:
Vitamin B, otherwise known as cobalamin, is an essential water-soluble vitamin that is obtained from animal derived dietary sources. Mutations in the genes that encode proteins responsible for cobalamin uptake, transport, or processing cause inborn errors of cobalamin metabolism, a group of disorders characterized by accumulation of homocysteine and methylmalonic acid, neurodevelopmental defects, ocular dysfunction, anemia, and failure to thrive. Mild to moderate craniofacial phenotypes have been observed but these phenotypes are not completely penetrant and have not been consistently recognized in the literature.
View Article and Find Full Text PDFSpectrum analysis of inborn errors of metabolism for expanded newborn screening in Xinjiang, China.
PeerJ
December 2024
Prenatal Diagnosis Center, Urumqi Maternal and Child Health Hospital, Urumqi, Xinjiang Uygur Autonomous Region, China.
To determine the disease spectrum and genetic characteristics of inborn errors of metabolism (IEM) in Xinjiang province in the northwest of China, 41,690 newborn babies were screening by tandem mass spectrometry from November 2018 to December 2021. Of these, 57 newborn babies were referred for genetic analysis by next-generation sequencing, which was validated by Sanger sequencing. A total of 36 newborn babies and one relative were diagnosed with IEM, and the overall positive predictive value was 29.
View Article and Find Full Text PDFClinical spectrum and genetic variation of six patients with methylmalonic aciduria (MMA); a report from Iran.
BMC Pediatr
December 2024
Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Shiraz, Iran.
Objective: Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder.
View Article and Find Full Text PDFA case series of Cypriot patients with CblC defect: Clinical, biochemical and molecular characteristics.
Mol Genet Metab Rep
December 2024
Biochemical Genetics Department, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Methylmalonic aciduria and homocystinuria, CblC type, is an inborn error of intracellular vitamin B12 (cobalamin) metabolism caused, in the majority of cases, by mutations in the gene. Five Cypriot patients (four males and one female) were diagnosed with a CblC defect. Age at diagnosis ranged from 10 days to 9 months.
View Article and Find Full Text PDFImproving methylmalonic acidemia (MMA) screening and MMA genotype prediction using random forest classifier in two Chinese populations.
Eur J Med Res
November 2024
National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, China.
Background: Methylmalonic acidemia (MMA) is one of the most common hereditary organic acid metabolism disorders that endangers the lives and health of infants and children. Early detection and intervention before the appearance of a newborn's clinical symptoms can control disease progression and prevent or mitigate its serious consequences.
Methods: 42,004 newborns from two Chinese populations were included in the study.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!