Abstract
Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene, leading to a variety of clinical manifestations. In October 2022, the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders, presenting primarily with cognitive decline, limb tremors, abnormal mental and behavioral symptoms, seizures, and gait disturbances. These symptoms had gradually developed over 5 years, worsening significantly in the past year. The patient's plasma homocysteine levels were 10 times higher than normal, and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei. Further genetic testing identified a paternal mutation c.1604G>A (p.R535Q) and a maternal mutation c.227T>G (p.L76R) of the MTHFR gene. After betaine supplementation, the plasma homocysteine levels decreased within a week, and the symptoms improved. The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency. The c.227T>G (p.L76R) mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency, but further research is needed to confirm its potential pathogenicity. Early treatment with betaine can fully reverse the symptoms.