Methylene tetrahydrofolate reductase (MTHFR) deficiency

Genetics and pathology

• This is caused by mutations in the methylene tetrahydrofolate reductase (MTHFR) gene
• The gene is responsible for remethylation of homocysteine to methionine 
• The transmission is autosomal recessive
• The mutations result in 5-methyltetrahydrofolate deficiency
• This is the main methyl donor for methionine synthesis
• It is required for the synthesis of S-adenosyl-methionine (SAM)
• Symptoms may be triggered by infection

References

1. Lossos A, Teltsh O, Milman T, et al. Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia. JAMA Neurol 2014; 71:901-904.
2. Huemer M, Mulder-Bleile R, Burda P, et al. Clinical pattern, mutations and in vitro residual activity in 33 patients with severe 5, 10 methylenetetrahydrofolate reductase (MTHFR) deficiency. J Inherit Metab Dis 2016; 39:115-124.
3. Baethmann M, Wendel U, Hoffmann GF, et al. Hydrocephalus internus in two patients with 5,10-methylenetetrahydrofolate reductase deficiency. Neuropediatrics 2000; 31:314-317.
4. Iida S, Nakamura M, Asayama S, et al. Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report. BMC Neurol 2017; 17:47.
5. Lin N, Jiang N, Dai Y, Gao J, Wang L. Adult-onset severe methylenetetrahydrofolate reductase deficiency characterized by reversible spastic paraplegia with a novel mutation. Neurol Sci 2016; 37:1735-1737.
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Related checklists

• Homocystinuria: clinical features
• Homocystinuria: differential diagnosis
• Homocystinuria: management
• Homocystinuria: surveillance