Mehmet Ali ŞAHİN, Adem GÜLER, Mehmet YOKUŞOĞLU, Murat TAVLAŞOĞLU

Methylenetetrahydrofolate reductase polymorphism in a case with atrial septal defect, deep venous thrombosis, thromboembolism and recurrent spontaneous abortion

Metilentetrahidrofolat redüktaz (MTHFR), homosisteini metionine dönüştüren folat metabolizmasında temel enzimdir. Metilentetrahidrofolat redüktaz gen polimorfizmi hiperhosisteinemiden sorumlu olup, doğuştan kalp defektleri, hiperkoagülasyon ve tekrarlayan abortuslara neden olur. Otuz yaşındaki kadın hasta atriyal septal defekt tanısıyla kliniğimize yönlendirildi. Hastanın tıbbi öyküsünde spontan abortus ile sonuçlanan iki gebeliği, derin venöz tromboz atakları, pulmoner emboli ve paradoks serebral emboli vardı. Genetik çalışma sonucunda heterozigot MTHFR C677T mutayonu saptandı. Spontan abortus veya derin ven trombozu veya paradoks serebral emboli ile birlikte doğuştan kalp hastalığı olan genç doğurgan kadın hastalarda MTHFR polimorfizminden şüphelenmeyi önermekteyiz

Atriyal septal defekt, derin ven trombozu, tromboembolizm ve te krarlayan spontan abortusu olan bir olguda metilentetrahidrofolat redüktaz polimorfizm

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolism, where homocysteine converted to methionine. Methylenetetrahydrofolate reductase gene polymorphism is responsible for hyperhomocysteinemia resulting congenital heart defects, hypercoagulable states and recurrent abortion. A 30-year- old female was referred to our department with the diagnosis of atrial septal defect. In her medical history, she had two pregnancies with spontaneous abortus, deep venous thrombosis attacks, pulmonary thromboembolism and paradoxical cerebral embolus. The genetic work- up revealed heterozygote MTHFR C677T mutation. We recommend suspecting MTHFR polymorphism in young fertile women with a history of spontaneous abortus or deep venous thrombosis or congenital heart disease with a paradoxical cerebral embolus.

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1.Schwahn B, Rozen R. Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. Am J Pharmacogenomics 2001;1:189-201.
2.Ma J, Stampfer MJ, Giovannucci E, Artigas C, Hunter DJ, Fuchs C, et al. Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 1997;57:1098-102.
3.Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995;10:111-3.
4.Palmieri V, Tufano A, Carmen Bonito M, Martino S, Sabatella M, Di Minno G, et al. Right-to-left shunt, atrial septal aneurysm and thrombophilia in patients with cryptogenic stroke or TIA vs. those with venous thrombo-embolism. Int J Cardiol 2008;130:99-102.
5.Wenstrom KD, Johanning GL, Johnston KE, DuBard M. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol 2001;184:806-12.
6.Brandalize AP, Bandinelli E, dos Santos PA, Roisenberg I, Schüler-Faccini L. Evaluation of C677T and A1298C polymorphisms of the MTHFR gene as maternal risk factors for Down syndrome and congenital heart defects. Am J Med Genet A 2009;149A:2080-7.
7.Grech V, Gatt M. Syndromes and malformations associated with congenital heart disease in a population-based study. Int J Cardiol 1999;68:151-6.
8.George L, Mills JL, Johansson AL, Nordmark A, Olander B, Granath F, et al. Plasma folate levels and risk of spontaneous abortion. JAMA 2002;288:1867-73.
9.Junker R, Kotthoff S, Vielhaber H, Halimeh S, Kosch A, Koch HG, et al. Infant methylenetetrahydrofolate reductase 677TT genotype is a risk factor for congenital heart disease. Cardiovasc Res 2001;51:251- 4.
10.Ibrahim S, El Dessokiy O. Prevalence of methylenetetrahydrofolate gene (MTHFR) C677T polymorphism among chronic hemodialysis patients and its association with cardiovascular disease: a cross-sectional analysis. Clin Exp Nephrol 2009;13:501-7.