Hyperhomocysteinemia complicated with developmental epileptic encephalopathy caused by compound heterozygous mutations of MTHFR gene: one case report and literature review.

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...

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Publicado en:Chinese Journal of Contemporary Neurology & Neurosurgery Vol. 25; no. 10; pp. 957 - 966
Autores principales: DU, Ya-kun, WANG, Li-hui, LI, Yan, CHEN, Fang, DONG, Lei, SUN, Su-zhen
Formato: case study diagnostic images tables/charts tracings Journal Article
Publicado: Chinese Journal of Contemporary Neurology & Neurosurgery Oct2025
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Oct2025
      vid: 25
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      pub: Chinese Journal of Contemporary Neurology & Neurosurgery
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        10.3969/j.issn.1672-6731.2025.10.012
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        atl: Hyperhomocysteinemia complicated with developmental epileptic encephalopathy caused by compound heterozygous mutations of MTHFR gene: one case report and literature review.
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        au:
          DU, Ya-kun
          WANG, Li-hui
          LI, Yan
          CHEN, Fang
          DONG, Lei
          SUN, Su-zhen
        affil: Department of Neurology, Hebei Children's Hospital, Shijiazhuang 050031, Hebei, China
      sug:
        subj:
          Hyperhomocysteinemia Risk Factors
          Developmental Disabilities Complications
          Epilepsy Complications
          Risk Assessment
          Mutation
          Female
          Child, Preschool
          Spasms, Infantile Etiology
          Electroencephalography
          Lennox-Gastaut Syndrome Physiopathology
          Seizures
          Magnetic Resonance Imaging
          Genetic Screening
          Homocysteine Blood
          Adrenocorticotropic Hormone Therapeutic Use
          Topiramate Administration and Dosage
          Neuroprotective Agents Therapeutic Use
          Vitamin B12 Therapeutic Use
          Carnitine Therapeutic Use
          Sequence Analysis
          Child, Preschool: 2-5 years
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        case study
        diagnostic images
        tables/charts
        tracings
        Journal Article
      ougenre: Article
    language: Chinese
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