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Peer-reviewedCC BYOrphanet Journal of Rare Diseases

Analysis of homocysteine levels in carriers with MMACHC gene variants

  • Yi Ding1
  • Yuxin Deng1
  • Haijuan Zhi1
  • Xia Zhan1
  • Wenjun Ji1
  • Zizhen Gong1
  • Lili Hao1
  • Lianshu Han1
  1. 1Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute of Pediatric Research, Shanghai Jiao Tong University School of Medicine
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Abstract

Objective Variants in the MMACHC gene cause combined methylmalonic acidemia (MMA) and homocystinuria, cobalamin C (cblC) type. This study aimed to determine whether heterozygous MMACHC variant carriers exhibit elevated plasma homocysteine (Hcy) levels and to explore the variant-type–specific biochemical effects. Methods In this prospective study, 301 MMACHC variant carriers and 304 controls were enrolled. Plasma Hcy levels, demographic characteristics, and clinical data were collected. Propensity score matching (PSM, 1:1) was performed to balance age and sex between groups. Generalized linear models were applied to investigate the correlation between MMACHC variant carriage and Hcy levels. Results After PSM, 173 carrier–control pairs were included. Carriers showed significantly higher Hcy levels (median 12.27 µmol/L, range 5.30–85.90) than controls (9.80 µmol/L, 3.10–53.30; P < 0.001). Both Male sex (β = 7.816, 95% CI:5.746–9.887) and MMACHC variant carriage (β = 5.741, 95%CI:3.743–7.740) were independently associated with elevated Hcy. Among carriers, missense variants, especially c.80A > G (p.Q27R), were correlated with higher Hcy levels. Conclusion Heterozygous MMACHC variant carriers had higher plasma Hcy levels than age- and sex-matched controls in this study. Missense variants and male sex tended to be associated with higher Hcy levels. These findings suggest that MMACHC variant carriers can present with biochemical abnormalities and associated with alterations in homocysteine metabolism.

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Cite

BibTeXRIS
BibTeX
@article{ding2026analysis,
  title = {{Analysis of homocysteine levels in carriers with MMACHC gene variants}},
  author = {Yi Ding and Yuxin Deng and Haijuan Zhi and Xia Zhan and Wenjun Ji and Zizhen Gong and Lili Hao and Lianshu Han},
  journal = {Orphanet Journal of Rare Diseases},
  year = {2026},
  month = jul,
  doi = {10.1186/s13023-026-04468-2},
  url = {https://doi.org/10.1186/s13023-026-04468-2},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Analysis of homocysteine levels in carriers with MMACHC gene variants
AU  - Yi Ding
AU  - Yuxin Deng
AU  - Haijuan Zhi
AU  - Xia Zhan
AU  - Wenjun Ji
AU  - Zizhen Gong
AU  - Lili Hao
AU  - Lianshu Han
PY  - 2026
DA  - 2026/07/01
JO  - Orphanet Journal of Rare Diseases
DO  - 10.1186/s13023-026-04468-2
UR  - https://doi.org/10.1186/s13023-026-04468-2
AB  - Objective Variants in the MMACHC gene cause combined methylmalonic acidemia (MMA) and homocystinuria, cobalamin C (cblC) type. This study aimed to determine whether heterozygous MMACHC variant carriers exhibit elevated plasma homocysteine (Hcy) levels and to explore the variant-type–specific biochemical effects. Methods In this prospective study, 301 MMACHC variant carriers and 304 controls were enrolled. Plasma Hcy levels, demographic characteristics, and clinical data were collected. Propensity score matching (PSM, 1:1) was performed to balance age and sex between groups. Generalized linear models were applied to investigate the correlation between MMACHC variant carriage and Hcy levels. Results After PSM, 173 carrier–control pairs were included. Carriers showed significantly higher Hcy levels (median 12.27 µmol/L, range 5.30–85.90) than controls (9.80 µmol/L, 3.10–53.30; P < 0.001). Both Male sex (β = 7.816, 95% CI:5.746–9.887) and MMACHC variant carriage (β = 5.741, 95%CI:3.743–7.740) were independently associated with elevated Hcy. Among carriers, missense variants, especially c.80A > G (p.Q27R), were correlated with higher Hcy levels. Conclusion Heterozygous MMACHC variant carriers had higher plasma Hcy levels than age- and sex-matched controls in this study. Missense variants and male sex tended to be associated with higher Hcy levels. These findings suggest that MMACHC variant carriers can present with biochemical abnormalities and associated with alterations in homocysteine metabolism.
SN  - 1750-1172
ER  -