Introduction: The c.677C>T mutation of the MTHFR gene, in the homozygous state (677TT), leads to reduced activity of methylenetetrahydrofolate reductase, a key enzyme in folate metabolism and methylation reactions. Its clinical expression is heterogeneous and may manifest as atypical psychiatric presentations, even in the absence of hyperhomocysteinemia, thereby limiting the diagnostic value of standard biological markers. Methods: We report the case of a female patient presenting with atypical psychotic symptoms partially resistant to conventional treatment. The biological workup was complemented by genetic analysis, including genotyping of the MTHFR gene. Results: Genotyping revealed a homozygous MTHFR c.677C>T mutation. Targeted metabolic management was initiated, based on supplementation with active folates (5-methyltetrahydrofolate) combined with vitamins B12 and B6, with biological monitoring. A gradual clinical improvement was observed, allowing a reduction in antidepressant treatment. Discussion/Conclusion: This case illustrates the value of MTHFR genotyping in identifying an underlying metabolic vulnerability in patients presenting with atypical or treatment-resistant clinical features. The clinical relevance of the 677TT genotype lies in an integrative and personalized approach, while its diagnostic limitations require cautious and contextualized interpretation of genetic findings.
Bahbouh et al. (Sun,) studied this question.