Article Text

Download PDFPDF
Case report
Adult-onset methylenetetrahydrofolate reductase deficiency
  1. Daniela Vieira1,
  2. Cristina Florindo2,
  3. Isabel Tavares de Almeida2 and
  4. Maria Carmo Macário1
  1. 1Serviço de Neurologia, Centro Hospitalar e Universitário de Coimbra EPE, Coimbra, Portugal
  2. 2Lab. Met&Gen, iMed, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal
  1. Correspondence to Dr Daniela Vieira; danielacgvieira{at}


Severe hyperhomocysteinemia (>100 µmol/L) is often associated with inborn errors of homocysteine metabolism. It manifests typically in neonatal period with developmental delay, hypotonia, feeding problems or failure to thrive. Adult-onset forms are rare and include less severe manifestations. Early diagnosis is crucial because effective treatment is available. A 23-year-old man presented with a 3-week history of speech and gait impairment, and numbness in lower limbs. Neurological examination revealed dysarthria, decreased vibratory sensation in both legs and appendicular and gait ataxia. Brain MRI revealed T2-hyperintense symmetric white matter lesions and cortical atrophy. He had folate and vitamin B12 deficiency, a markedly elevated serum homocysteine and low methionine. Despite vitamin supplementation homocysteine levels remained elevated. Molecular studies of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene revealed a new pathogenic mutation (c.1003C>T (p.Arg335Cys)) and a polymorphism (C677T (p.Ala222Val)) associated with hyperhomocysteinemia, both in homozygosity. The patient started betaine with clinical and biochemical improvement.

  • neuro genetics
  • medical management
  • metabolic disorders

Statistics from


  • Contributors Report was written by DV and MCM, and it was revised by ITdA and CF.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.