AUTHOR=Cheng Siqi , Chen Weihong , Zhao Mingmin , Xing Xing , Zhao Lei , Ren Bowen , Li Na 

TITLE=Case report: A late-onset cobalamin C defect first presenting as a depression in a teenager

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.1012558

DOI=10.3389/fgene.2022.1012558

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> The cobalamin C (cblC) defect, a common inborn disorder of cobalamin metabolism due to a genetic mutation in <italic>MMACHC</italic>, can cause combined methylmalonic acid and homocysteine accumulation in blood, urine, or both. In this article, a late-onset case was reported, and the patient first presented with depression identified with the <italic>MMACHC</italic> gene. We summarized the clinical features of the cblC defect, the relationship between genotype and phenotype, and the clinical experience concerning the diagnosis and treatment of the cblC defect.</p><p><bold>Case presentation:</bold> Initially presented with depression, the 16-year-old female patient showed progressive abnormal gait and bilateral lower limb weakness after 3 months. Blood routine examination suggested severe hyperhomocysteinemia, and screening for urine organic acids found elevated methylmalonic acid. Family gene sequencing showed mutations detected in <italic>MMACHC</italic>. She had a compound heterozygous mutation, while the c.271dupA (p.R91Kfs∗14) was only detected in her father and the c.482 G&gt;A (p.R161Q) was only detected in her mother. Hence, she was diagnosed with a cblC defect and treated with B vitamin supplements. The muscle strength of both lower limbs improved notably.</p><p><bold>Conclusion:</bold> This case indicated that depression could be a presenting sign of cblC-type methylmalonic aciduria and homocysteinemia, and enhanced the genotype–phenotype relationship of the cblC defect, which will contribute to further understanding of this emerging disease.</p>