Year 2019, Volume 7 , Issue 3, Pages 19 - 24 2019-12-31

Nöral tüp defekti etkilenen çocuklarda MTHFR enziminin kantitatif değerlendirilmesi
Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children


Background: Neural tube defect (NTD) pathogenesis is still not understanding well and controversial. Maternal Methylene Tetrahydrofolate Reductase (MTHFR) is an important enzyme controlling levels of methionine, homocysteine, and folic acid in the cycle of folate metabolism which has a considerable relationship with NTD development, while the role fetal MTHFR enzyme was not known till now.

Objective: To evaluate the serum level of MTHFR in NTDs affected children to search if it is related to the defect pathogenesis.

Patients and methods: A cohort study was performed during 2017- 2018 in Al- Batool hospital. A newly delivered NTD affected babies were included, serum level of MTHFR was measured by ELISA, results were compared to that of healthy neonates. SPSS version 22 was used for statistical analysis.

Results: Forty six infants with NTD were included, spina bifida (n=39, 84.8%) and cranial NTD (7, 15.2%), females: males ratio was 1:1.35. MTHFR enzyme readings showed wide range in both healthy and NTD affected infants, generally, for cases they were insignificantly higher than that of control group (p value= 0.115); they were unrelated with the defect whether cranial or spinal, p value (0.264 ). Enzyme level significantly higher in NTD affected infants whom mothers aged more 35 yrs old (p value= 0.00) and insignificantly higher in babies whom mothers received folic acid than others.

Conclusion: It was found no role of fetal enzyme level in pathogenesis of NTD, in contrast, there was high MTHFR level in affected children, which might reflect a compensatory mechanism. 

MTHFR, Neural tube defect, Congenital, Folate
  • Au K.S., Ashley-Koch A., Northrup H. Epidemiologic and genetic aspects of spina bifida and other neural tube defects. Dev. Disabil. Res. Rev. 2010;16:6–15.
  • Lynch S.A. Non-multifactorial neural tube defects. Am. J. Med. Genet. C Semin. Med. Genet. 2005;135C:69–76.
  • Blom H.J. Folic acid, methylation and neural tube closure in humans. Birth Defects Res. 2009;85:295–302.
  • Blom H.J., Shaw G.M., den Heijer M., Finnell R.H. Neural tube defects and folate: Case far from closed. Nat. Rev. Neurosci. 2006;7:724–731.
  • Blom H.J., Smulders Y. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J. Inherit. Metab. Dis. 2011;34:75–81.
  • De Marco P., Merello E., Cama A., Kibar Z., Capra V. Human neural tube defects: Genetic causes and prevention. Biofactors. 2011;37:261–268.
  • Van der Put N.M., van Straaten H.W., Trijbels F.J., Blom H.J. Folate, homocysteine and neural tube defects: An overview. Exp. Biol. Med. 2001;226:243–270.
  • Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000;151:862–877.
  • Algasham A, Ismail H, Dewaidar M, Settin AA. Methylenetetrahydrofolate reductase and angiotensin-converting enzyme gene polymorphisms among saudi population from qassim region. Genet Test Mol Biomarkers2009;13:817-20.
  • Scott JM, Weir DG, Molloy A, McPartlin J, Daly L, Kirke P. Folic acid metabolism and mechanisms of neural tube defects. Ciba Found Symp. 1994;181:180- 91.
  • Apolline Imbard, Jean-François Benoist, Henk J. Blom. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013 Sep; 10(9): 4352–4389.
  • Van der Put NM, Blom HJ. Neural tube defects and a disturbed folate dependent homocysteine metabolism. Eur J ObstetGynecolReprod Biol. 2000;92:57–61. 13. Van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. ExpBiol Med (Maywood) 2001;226:243–270.
  • Kruger WD, Evans AA, Wang L, Malinow MR, Duell PB, Anderson PH, et al. Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid. Mol Genet Metab. 2000;70:53–60.
  • Peadar N Kirke, James L Mills, Anne M Molloy, Lawrence C Brody, Valerie B O'Leary, Leslie Daly, et al. Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study. BMJ. 2004 Jun 26; 328(7455): 1535–1536.
  • Marini NJ, Hoffmann TJ, Lammer EJ, Hardin J, Lazaruk K, Stein JB, et al. A genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis. PLoS One. 2011; 6(11):e28408.
  • Weizhi Zhao, Bridget S. Mosley, Mario A. Cleves, StepanMelnyk, S. Jill James, and Charlotte A. Hobbs. Neural Tube Defects and Maternal Biomarkers of Folate, Homocysteine, and Glutathione Metabolism. Birth Defects Res A ClinMolTeratol. 2006 Apr; 76(4): 230–236.
  • Chango A, Boisson F, Barbé F, Quilliot D, Droesch S, Pfister M, et al. The effect of 677CT and 1298AC mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects. Br J Nutr 2000;83(6):593-596.
  • Goyette, P., Sumner, J. S., Milos, R., Duncan, A. M. V., Rosenblatt, D. S., Matthews, R. G., et al. Human methylenetetrahydrofolatereductase: isolation of cDNA, mapping and mutation identification. Nature Genet. 1994;7:195–200.
  • Kluijtmans, L. A. J., Wendel, U., Stevens, E. M. B., van den Heuvel, L. P. W. J., Trijbels, F. J. M., and Blom, H. J. Identification of four novel mutations in severe methylene tetrahydrofolate reductase deficiency. Eur. J. Hum. Genet. 1998;6: 257–265.
  • Sibani, S., Christensen, B., O’Ferrell, E., Saadi, I., Hiou-Tim, F., Rosenblatt, D. S., et al. Characterization of six novel mutations in the methylene tetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Hum. Mutat. 2000;15:280–287.
  • Van der Put NM, Gabreëls F, Stevens EM, Smeitink JA, Trijbels FJ, Eskes TK. et al. A second common mutation in the methylene tetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? 1998;62:1044-1051.
  • Trembath D, Sherbondy AL, Vandyke DC, Shaw GM, Todoroff K, Lammer EJ,, et al. Analysis of select folate pathway genes, PAX3, and human T in a Midwestern neural tube defect population. 1999;59:331-341.
  • Rampersaud E, Melvin EC, Siegel D, Mehltretter L, Dickerson ME, George TM, et al. NTD Collaborative Group. Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects. 2003;63:210-214.
  • Volcik KA, Shaw GM, Lammer EJ, Zhu H, Finnell RH. Evaluation of infant methylene tetrahydrofolate reductase genotype, maternal vitamin use, and risk of high versus low level spina bifida defects. Birth Defects Res Part. A 2003;67:154-157.
  • Botto, L. D. and Yang, Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: A HuGE review. Am. J. Epidemiol.2000;9:862–877.
  • Christianson AL, Howson CP, Modell B. Global report on birth defects: the hidden toll of dying and disabled children. White Plains (NY): March of Dimes Birth Defects Foundation; 2006.
  • World Health Organization. Global health estimates (GHE)–Cause-specific mortality. 2015.Available: Accessed 2015 Apr 14.
  • World Health Organization. Global health estimates (GHE)–Disease burden. 2015. Available: Accessed 2015 Apr 14.
  • Blencowe H, Cousens S, Modell B, Lawn J. Folic acid to reduce neonatal mortality from neural tube disorders. International Journal of Epidemiology. 2010; 39 (Suppl 1): i110–i121.
  • Laura Dean. Methylene tetrahydrofolate Reductase Deficiency. In: Medical Genetics Summaries Editors: Victoria Pratt, Howard McLeod, Wendy Rubinstein, Laura Dean, Brandi Kattman, Associate Editor, and Adriana Malheiro, Editor-in-chief. Bethesda (MD): National Center for Biotechnology Information (US); 2012
  • Schoner K, Axt-Fliedner R, Bald R, Fritz B, Kohlhase J, Kohl T, et al. Fetal Pathology of Neural Tube Defects - An Overview of 68 Cases. Geburtshilfe Frauenheilkd. 2017 May;77(5):495-507
  • Asindi A, Al-Shehri A. Neural tube defects in the Asir Region of Saudi Arabia. Ann Saudi Med. 2001 Jan-Mar; 21(1-2):26-9
  • Canfield MA, Marengo L, Ramadhani TA, Suarez L, Brender JD, Scheuerle A. The prevalence and predictors of anencephaly and spina bifida in Texas. Paediatr Perinat Epidemiol. 2009 Jan; 23(1):41-50.
  • Petrova JG, Vaktskjold A. The incidence of neural tube defects in Norway and the Arkhangelskaja Oblast in Russia and the association with maternal age. Acta Obstet Gynecol Scand. 2009; 88(6):667-72.
  • Mohammad Jafar Golalipour, Mostafa Qorbani, Arezo Mirfazeli, and Elham Mobasheri. Risk Factors of Neural Tube Defects in Northern Iran. Iran Red Crescent Med J. 2014 Jun; 16(6): 7940.
  • Al-Ani ZR, Al-Hiali SJ, Al-Mehimdi SM. Neural tube defects among neonates delivered in Al-Ramadi Maternity and Children's Hospital, western Iraq. Saudi Med J. 2010 Feb; 31(2):163-9.
  • Mustafa A M Salih, Waleed R Murshid, Ashry Gad Mohamed, Lena C Ignacio, Julie E de Jesus, Rubana Baabbad, et al. Risk factors for neural tube defects in Riyadh City, Saudi Arabia: Case-control study. Sudan J Paediatr. 2014; 14(2): 49–60.
  • Teebi AS, Talaat F I. Genetic disorders among the Egyptians. In: Genetic disorders among Arab populations New york: Oxford University Press; 1997. page 191–207.
  • Zlotogora J. Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am J Med Genet. 1997 Feb 11; 68(4):472-5.
  • Mahadevan B, Bhat BV. Neural tube defects in Pondicherry. Indian J Pediatr. 2005 Jul; 72(7):557-9.
Primary Language en
Subjects Health Care Sciences and Services
Journal Section Original Articles

Orcid: 0000-0002-8924-4946
Author: Najdat SHUKUR MAHMOOD (Primary Author)
Country: Iraq


Publication Date : December 31, 2019

Bibtex @research article { pprjournal614552, journal = {Pediatric Practice and Research}, issn = {2147-6470}, address = {}, publisher = {MediHealth Academy Yayıncılık}, year = {2019}, volume = {7}, pages = {19 - 24}, doi = {}, title = {Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children}, key = {cite}, author = {Shukur Mahmood, Najdat} }
APA Shukur Mahmood, N . (2019). Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children . Pediatric Practice and Research , 7 (3) , 19-24 . Retrieved from
MLA Shukur Mahmood, N . "Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children" . Pediatric Practice and Research 7 (2019 ): 19-24 <>
Chicago Shukur Mahmood, N . "Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children". Pediatric Practice and Research 7 (2019 ): 19-24
RIS TY - JOUR T1 - Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children AU - Najdat Shukur Mahmood Y1 - 2019 PY - 2019 N1 - DO - T2 - Pediatric Practice and Research JF - Journal JO - JOR SP - 19 EP - 24 VL - 7 IS - 3 SN - 2147-6470- M3 - UR - Y2 - 2019 ER -
EndNote %0 Pediatric Practice and Research Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children %A Najdat Shukur Mahmood %T Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children %D 2019 %J Pediatric Practice and Research %P 2147-6470- %V 7 %N 3 %R %U
ISNAD Shukur Mahmood, Najdat . "Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children". Pediatric Practice and Research 7 / 3 (December 2020): 19-24 .
AMA Shukur Mahmood N . Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children. pediatr pract res. 2019; 7(3): 19-24.
Vancouver Shukur Mahmood N . Quantitative Evaluation of MTHFR Enzyme in Neural Tube Defect Affected Children. Pediatric Practice and Research. 2019; 7(3): 19-24.