Late-onset cobalamin C defect with a rare MMACHC c.457 C > T variant: a case report and literature review.
- 1Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China.
- 2Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China. [email protected].
- 3Department of Pediatrics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530000, China. [email protected].
Abstract
Background
Cobalamin C (cblC) defect, also referred to as combined methylmalonic acidemia and homocystinuria, is the most common inborn error of intracellular cobalamin metabolism. Late-onset cblC defect often presents with atypical and heterogeneous manifestations, particularly neuropsychiatric symptoms, which may lead to misdiagnosis and delayed treatment.Case presentation
We report a 13-year-old girl with late-onset cblC defect who presented with progressive cognitive impairment, psychiatric and behavioral abnormalities, and motor dysfunction. Because of these atypical manifestations, she was initially misdiagnosed with autoimmune encephalitis. Laboratory evaluation showed markedly elevated plasma total homocysteine, decreased methionine, mildly increased propionylcarnitine with elevated C3/C2 and C3/C0 ratios, and markedly increased urinary methylmalonic acid and methylcitrate. Genetic testing identified compound heterozygous pathogenic variants in the MMACHC gene: c.482G > A (p.Arg161Gln, maternally inherited) and c.457 C > T (p.Arg153Ter), the latter being rarely reported in China. Following treatment with hydroxocobalamin, folate, betaine, and L-carnitine, the patient showed marked biochemical improvement and partial clinical recovery, although residual cognitive impairment and gait disturbance persisted.Conclusions
This case expands the genotypic spectrum of cblC defect in China and highlights the importance of metabolic screening and genetic testing in children and adolescents with otherwise unexplained neuropsychiatric manifestations. Early recognition and targeted treatment are crucial for improving long-term neurological outcomes.
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BibTeX
@article{huang2026lateonset,
title = {{Late-onset cobalamin C defect with a rare MMACHC c.457 C > T variant: a case report and literature review.}},
author = {Qingmei Huang and Zhenmei Liao and Honghua Li and Xiu Lu and Lingdong Zeng},
journal = {BMC pediatrics},
year = {2026},
month = jul,
doi = {10.1186/s12887-026-07352-x},
url = {https://europepmc.org/article/MED/42897485},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Late-onset cobalamin C defect with a rare MMACHC c.457 C > T variant: a case report and literature review.
AU - Qingmei Huang
AU - Zhenmei Liao
AU - Honghua Li
AU - Xiu Lu
AU - Lingdong Zeng
PY - 2026
DA - 2026/07/01
JO - BMC pediatrics
DO - 10.1186/s12887-026-07352-x
UR - https://europepmc.org/article/MED/42897485
AB - Background Cobalamin C (cblC) defect, also referred to as combined methylmalonic acidemia and homocystinuria, is the most common inborn error of intracellular cobalamin metabolism. Late-onset cblC defect often presents with atypical and heterogeneous manifestations, particularly neuropsychiatric symptoms, which may lead to misdiagnosis and delayed treatment.Case presentation We report a 13-year-old girl with late-onset cblC defect who presented with progressive cognitive impairment, psychiatric and behavioral abnormalities, and motor dysfunction. Because of these atypical manifestations, she was initially misdiagnosed with autoimmune encephalitis. Laboratory evaluation showed markedly elevated plasma total homocysteine, decreased methionine, mildly increased propionylcarnitine with elevated C3/C2 and C3/C0 ratios, and markedly increased urinary methylmalonic acid and methylcitrate. Genetic testing identified compound heterozygous pathogenic variants in the MMACHC gene: c.482G > A (p.Arg161Gln, maternally inherited) and c.457 C > T (p.Arg153Ter), the latter being rarely reported in China. Following treatment with hydroxocobalamin, folate, betaine, and L-carnitine, the patient showed marked biochemical improvement and partial clinical recovery, although residual cognitive impairment and gait disturbance persisted.Conclusions This case expands the genotypic spectrum of cblC defect in China and highlights the importance of metabolic screening and genetic testing in children and adolescents with otherwise unexplained neuropsychiatric manifestations. Early recognition and targeted treatment are crucial for improving long-term neurological outcomes.
SN - 1471-2431
ER -