Severe 5, 10‐methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia. (30th January 2018)

• Record Type: Journal Article
• Authors: Perna, A.; Masciullo, M.; Modoni, A.; Cellini, E.; Parrini, E.; Ricci, E.; Donati, A. M.; Silvestri, G.
• Is Part Of: European journal of neurology. Volume 25:Number 3(2018)
• Page Start: 602
• Page End: 605
• Publication Date: 2018-01-30
• Subjects: betain -- cerebral white matter disease -- complicated hereditary spastic paraplegia -- hyperhomocysteinemia -- severe 5, 10‐methylenetetrahydrofolate reductase deficiency; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.13557
• Languages: English
• ISSNs: 1351-5101

Abstract

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.