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5,10-Methylenetetrahydrofolate reductase deficiency

MedGen UID:
82824
•Concept ID:
C0268615
•
Disease or Syndrome
Synonyms: 5' 10' Methylenetetrahydrofolate Reductase Deficiency; 5' 10' Methylenetetrahydrofolate Reductase Deficiency (MTHFR); Methylenetetrahydrofolate reductase deficiency
SNOMED CT: Methylenetetrahydrofolate reductase deficiency (41797007); 5,10-Methylenetetrahydrofolate reductase deficiency (41797007)

Definition

A rare disorder associated with mental retardation, spasticity, and early death. [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV5,10-Methylenetetrahydrofolate reductase deficiency

Professional guidelines

PubMed

Betaine dose and treatment intervals in therapy for homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.
Sakura N, Ono H, Nomura S, Ueda H, Fujita N
J Inherit Metab Dis 1998 Feb;21(1):84-5. doi: 10.1023/a:1005331902497. PMID: 9501279

Recent clinical studies

Etiology

Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency.
Ucar SK, Koroğlu OA, Berk O, Yalaz M, Kültürsay N, Blom HJ, Coker M
Eur J Pediatr 2010 Feb;169(2):241-3. Epub 2009 May 12 doi: 10.1007/s00431-009-0997-x. PMID: 19434424
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.
Strauss KA, Morton DH, Puffenberger EG, Hendrickson C, Robinson DL, Wagner C, Stabler SP, Allen RH, Chwatko G, Jakubowski H, Niculescu MD, Mudd SH
Mol Genet Metab 2007 Jun;91(2):165-75. Epub 2007 Apr 3 doi: 10.1016/j.ymgme.2007.02.012. PMID: 17409006
Homocysteine-betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency.
Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, Mar MH, Zeisel SH, Castro C, Garrow T, Rozen R
FASEB J 2003 Mar;17(3):512-4. Epub 2003 Jan 22 doi: 10.1096/fj.02-0456fje. PMID: 12551843
Central and peripheral nervous system pathology of homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.
Nishimura M, Yoshino K, Tomita Y, Takashima S, Tanaka J, Narisawa K, Kurobane I
Pediatr Neurol 1985 Nov-Dec;1(6):375-8. doi: 10.1016/0887-8994(85)90076-1. PMID: 2854737

Diagnosis

Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
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 AM, Silvestri G
Eur J Neurol 2018 Mar;25(3):602-605. Epub 2018 Jan 30 doi: 10.1111/ene.13557. PMID: 29284203
Insights into severe 5,10-methylenetetrahydrofolate reductase deficiency: molecular genetic and enzymatic characterization of 76 patients.
Burda P, Schäfer A, Suormala T, Rummel T, Bürer C, Heuberger D, Frapolli M, Giunta C, Sokolová J, Vlášková H, Kožich V, Koch HG, Fowler B, Froese DS, Baumgartner MR
Hum Mutat 2015 Jun;36(6):611-21. Epub 2015 Apr 27 doi: 10.1002/humu.22779. PMID: 25736335
Severe 5,10-methylenetetrahydrofolate reductase deficiency and two MTHFR variants in an adolescent with progressive myoclonic epilepsy.
D'Aco KE, Bearden D, Watkins D, Hyland K, Rosenblatt DS, Ficicioglu C
Pediatr Neurol 2014 Aug;51(2):266-70. Epub 2014 Apr 13 doi: 10.1016/j.pediatrneurol.2014.04.005. PMID: 25079578
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.
Strauss KA, Morton DH, Puffenberger EG, Hendrickson C, Robinson DL, Wagner C, Stabler SP, Allen RH, Chwatko G, Jakubowski H, Niculescu MD, Mudd SH
Mol Genet Metab 2007 Jun;91(2):165-75. Epub 2007 Apr 3 doi: 10.1016/j.ymgme.2007.02.012. PMID: 17409006

Therapy

Severe 5,10-methylenetetrahydrofolate reductase deficiency and two MTHFR variants in an adolescent with progressive myoclonic epilepsy.
D'Aco KE, Bearden D, Watkins D, Hyland K, Rosenblatt DS, Ficicioglu C
Pediatr Neurol 2014 Aug;51(2):266-70. Epub 2014 Apr 13 doi: 10.1016/j.pediatrneurol.2014.04.005. PMID: 25079578
Prevention of brain disease from severe 5,10-methylenetetrahydrofolate reductase deficiency.
Strauss KA, Morton DH, Puffenberger EG, Hendrickson C, Robinson DL, Wagner C, Stabler SP, Allen RH, Chwatko G, Jakubowski H, Niculescu MD, Mudd SH
Mol Genet Metab 2007 Jun;91(2):165-75. Epub 2007 Apr 3 doi: 10.1016/j.ymgme.2007.02.012. PMID: 17409006
Homocysteine-betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency.
Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, Mar MH, Zeisel SH, Castro C, Garrow T, Rozen R
FASEB J 2003 Mar;17(3):512-4. Epub 2003 Jan 22 doi: 10.1096/fj.02-0456fje. PMID: 12551843
Betaine dose and treatment intervals in therapy for homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency.
Sakura N, Ono H, Nomura S, Ueda H, Fujita N
J Inherit Metab Dis 1998 Feb;21(1):84-5. doi: 10.1023/a:1005331902497. PMID: 9501279
N-5,10-methylenetetrahydrofolate reductase deficiency and schizophrenia: a working hypothesis.
Mudd SH, Freeman JM
J Psychiatr Res 1974;11:259-62. doi: 10.1016/0022-3956(74)90101-0. PMID: 4461794

Prognosis

Titration of betaine therapy to optimize therapy in an infant with 5,10-methylenetetrahydrofolate reductase deficiency.
Ucar SK, Koroğlu OA, Berk O, Yalaz M, Kültürsay N, Blom HJ, Coker M
Eur J Pediatr 2010 Feb;169(2):241-3. Epub 2009 May 12 doi: 10.1007/s00431-009-0997-x. PMID: 19434424
Folate-induced reversal of leukoencephalopathy and intellectual decline in methylene-tetrahydrofolate reductase deficiency: variable response in siblings.
Tallur KK, Johnson DA, Kirk JM, Sandercock PA, Minns RA
Dev Med Child Neurol 2005 Jan;47(1):53-6. doi: 10.1017/s0012162205000095. PMID: 15686290
Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency.
Selzer RR, Rosenblatt DS, Laxova R, Hogan K
N Engl J Med 2003 Jul 3;349(1):45-50. doi: 10.1056/NEJMoa021867. PMID: 12840091

Clinical prediction guides

Homocysteine-betaine interactions in a murine model of 5,10-methylenetetrahydrofolate reductase deficiency.
Schwahn BC, Chen Z, Laryea MD, Wendel U, Lussier-Cacan S, Genest J Jr, Mar MH, Zeisel SH, Castro C, Garrow T, Rozen R
FASEB J 2003 Mar;17(3):512-4. Epub 2003 Jan 22 doi: 10.1096/fj.02-0456fje. PMID: 12551843
Purine deoxynucleosides and adenosine dialdehyde decrease 5-amino-4-imidazolecarboxamide (Z-base)-dependent purine nucleotide synthesis in cultured T and B lymphoblasts.
Boss GR
Biochem J 1987 Mar 1;242(2):425-31. doi: 10.1042/bj2420425. PMID: 3109390Free PMC Article
Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency.
Kanwar YS, Manaligod JR, Wong PW
Pediatr Res 1976 Jun;10(6):598-609. doi: 10.1203/00006450-197606000-00008. PMID: 1272636

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