| Sumario: | Objective To investigate the clinical correlation between hyperhomocysteinemia caused by MTHFR gene mutation and developmental epileptic encephalopathy (DEE), as well as the corresponding intervention strategies. Methods and Results A female child, aged 2 years and 5 months, presented with infantile spasm (IS) as the initial symptom. Video electroencephalography (VEEG) showed highly irregular, which progressively evolved into generalized multifocal discharges consistent with Lennox-Gastaut syndrome (LGS), accompanied by tonic clonic seizure. MRI showed delayed myelination and leukomalacia. Genetic testing showed the compound heterozygous mutations in the MTHFR gene: c. 154C > T (p. Arg52X) and c. 889T > C (p. Tyr297His). These were inherited from her mother [c. 154C > T (p. Arg52X)] and father [c.889T > C (p.Tyr297His)]. This genetic testing resulted in severely elevated serum homocysteine level of 161 μmol/L. Following treatment with a combination of antiepileptic seizure medication (ASM), betaine and B vitamins, the homocysteine level decreased to 70 μmol/L and seizure frequency was reduced. However, significant neurodevelopmental delay persisted. Conclusions The novel compound heterozygous mutations of MTHFR gene [c.154C > T (p.Arg52X) and c.889T > C (p.Tyr297His)] expand the spectrum of known MTHFR gene mutation. These mutations disrupt folate metabolism, leading to severe hyperhomocysteinemia and DEE. This case underscores the critical importance of early metabolic intervention for improving clinical outcomes.
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