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Severe 5,10‐methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia
Author(s) -
Perna A.,
Masciullo M.,
Modoni A.,
Cellini E.,
Parrini E.,
Ricci E.,
Donati A. M.,
Silvestri G.
Publication year - 2018
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.13557
Subject(s) - methylenetetrahydrofolate reductase , medicine , hereditary spastic paraplegia , homocystinuria , pediatrics , spastic , paraplegia , cerebral palsy , physical therapy , genetics , spinal cord , psychiatry , methionine , amino acid , gene , genotype , biology , phenotype
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.