Open AccessAdult-onset methylenetetrahydrofolate reductase deficiency
Author(s) -
Daniela Vieira,
Cristina Florindo,
Isabel Tavares de Almeida,
Maria Carmo Macário
Publication year - 2020
Publication title -
bmj case reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.231
H-Index - 26
ISSN - 1757-790X
DOI - 10.1136/bcr-2019-232241
Subject(s) - hyperhomocysteinemia , medicine , methylenetetrahydrofolate reductase , homocysteine , hypotonia , failure to thrive , ataxia , gait ataxia , endocrinology , homocystinuria , dysarthria , pediatrics , gastroenterology , methionine , allele , genetics , audiology , amino acid , psychiatry , biology , gene
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 B 12 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.