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

A. Perna, M. Masciullo, A. Modoni, E. Cellini, E. Parrini, E. Ricci, A. M. Donati, G. Silvestri

Research output: Contribution to journalArticle

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 mumol/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.
Original languageEnglish
Pages (from-to)602-605
Number of pages4
JournalEuropean Journal of Neurology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Hereditary Spastic Paraplegia
Spastic Paraparesis
Software Design
Methylenetetrahydrofolate Reductase (NADPH2)
Betaine
Polyneuropathies
Electromyography
Neuroimaging
Vitamins
Intellectual Disability
Siblings
Magnetic Resonance Imaging
Amino Acids
Brain
Methylenetetrahydrofolate reductase deficiency
Therapeutics

Cite this

Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia. / Perna, A.; Masciullo, M.; Modoni, A.; Cellini, E.; Parrini, E.; Ricci, E.; Donati, A. M.; Silvestri, G.

In: European Journal of Neurology, Vol. 25, No. 3, 01.03.2018, p. 602-605.

Research output: Contribution to journalArticle

Perna, A. ; Masciullo, M. ; Modoni, A. ; Cellini, E. ; Parrini, E. ; Ricci, E. ; Donati, A. M. ; Silvestri, G. / Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia. In: European Journal of Neurology. 2018 ; Vol. 25, No. 3. pp. 602-605.
@article{7904ad274dc544dd87e94812602d7cde,
title = "Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia",
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 mumol/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.",
author = "A. Perna and M. Masciullo and A. Modoni and E. Cellini and E. Parrini and E. Ricci and Donati, {A. M.} and G. Silvestri",
note = "LR: 20190204; CI: (c) 2017; JID: 9506311; EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)); Methylenetetrahydrofolate reductase deficiency; OTO: NOTNLM; 2017/08/18 00:00 [received]; 2017/12/18 00:00 [accepted]; 2017/12/29 06:00 [pubmed]; 2019/02/05 06:00 [medline]; 2017/12/29 06:00 [entrez]; ppublish",
year = "2018",
month = "3",
day = "1",
doi = "10.1111/ene.13557 [doi]",
language = "English",
volume = "25",
pages = "602--605",
journal = "European Journal of Neurology",
issn = "1351-5101",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "3",

}

TY - JOUR

T1 - Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia

AU - Perna, A.

AU - Masciullo, M.

AU - Modoni, A.

AU - Cellini, E.

AU - Parrini, E.

AU - Ricci, E.

AU - Donati, A. M.

AU - Silvestri, G.

N1 - LR: 20190204; CI: (c) 2017; JID: 9506311; EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2)); Methylenetetrahydrofolate reductase deficiency; OTO: NOTNLM; 2017/08/18 00:00 [received]; 2017/12/18 00:00 [accepted]; 2017/12/29 06:00 [pubmed]; 2019/02/05 06:00 [medline]; 2017/12/29 06:00 [entrez]; ppublish

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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 mumol/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.

AB - 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 mumol/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.

U2 - 10.1111/ene.13557 [doi]

DO - 10.1111/ene.13557 [doi]

M3 - Article

VL - 25

SP - 602

EP - 605

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 3

ER -