Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia

Eur J Neurol. 2018 Mar;25(3):602-605. doi: 10.1111/ene.13557. Epub 2018 Jan 30.

Abstract

Background and purpose: Juvenile- or adult-onset forms of severe 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency manifesting as complicated hereditary spastic paraplegia have rarely been described.

Methods: Two siblings with mental retardation developed a progressive spastic paraparesis in their late teens. Their diagnostic assessment included extensive neurophysiologic, neuroimaging and metabolic studies.

Results: Brain magnetic resonance imaging showed occipital white matter alterations, and electromyography documented a mixed polyneuropathy. Severe hyperhomocisteinemia (>150 μmol/L) associated with the characteristic amino acid profile suggested a diagnosis of severe MTHFR deficiency, confirmed by MTHFR direct sequencing. Treatment with betaine and vitamins benefitted patients' symptoms and diagnostic features.

Conclusions: Severe MTHFR deficiency can be a rare, treatable cause of autosomal recessive complicated hereditary spastic paraplegia. Its screening should be part of the diagnostic flowchart for these disorders.

Keywords: betain; cerebral white matter disease; complicated hereditary spastic paraplegia; hyperhomocysteinemia; severe 5,10-methylenetetrahydrofolate reductase deficiency.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Homocystinuria / diagnosis*
  • Humans
  • Intellectual Disability / diagnosis*
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / deficiency*
  • Muscle Spasticity / diagnosis*
  • Psychotic Disorders / diagnosis
  • Siblings
  • Spastic Paraplegia, Hereditary / diagnosis*
  • Young Adult

Substances

  • Methylenetetrahydrofolate Reductase (NADPH2)

Supplementary concepts

  • Methylenetetrahydrofolate reductase deficiency