Mehmet ALAKAYA, Ali Ertuğ ARSLANKÖYLÜ, Erdem AK, Selma ÜNAL, Çetin OKUYAZ, Fatma DURAK

Recurrent Ischemic Stroke in A Child with Thiamine ResponsiveMegaloblastic Anemia Syndrome

Thiamine responsive megaloblastic anemia syndrome (TRMA) (OMIM 249270) is a rare, autosomal recessive inherited disorder characterized by a triad of megaloblastic anemia, diabetes mellitus and sensorineural deafness. Mutations in the SLC19A2 gene, encoding a high-affinity thiamine transporter protein, THTR-1, are responsible for the clinical features associated with TRMA.Here, we report a 20 month-old boy with TRMA. During evaluation of recurrent stroke and megaloblastic anemia homozygous mutation in SLC19A2 gene (c.242-243 insA) was detected. Additionally ho-mozygote MTHFR C677 and heterozygote MTHFR A1298 mutations were also detected in thrombosis panel. As far as we know this is the first TRMA case with homozygote MTHFR C677 and heterozygote MTHFR A1298 mutations in the literature.

PDF

___

1.Borgna-Pignatti C, Azzalli M, Pedretti S. Thiami-ne-responsive megaloblastic anemia syndrome: long term follow-up. J Pediatr 2009; 155: 295-7.

2.Bay A, Keskin M, Hizli S, Uygun H, Dai A, Gum-ruk F. Thiamine-responsive megaloblastic anemia syndrome. Int J Hematol 2010; 92: 524-6.

3.Ricketts CJ, Minton JA, Samuel J et al. Thiamine responsive megaloblastic anaemia syndrome: long-term follow-up and mutation analysis of seven fa-milies. Acta Paediatr 2006; 95: 99-104.

4.Ozdemir MA, Akcakus M, Kurtoglu S, Gunes T, Torun YA. TRMA syndrome (thiamine-responsive megaloblastic anemia): a case report and review of the literature. Pediatric Diabetes 2002; 3: 205-9.

5.Setoodeh A, Haghighi A, Saleh-Gohari N, Ellard S, Haghighi A. Identification of a SLC19A2 non-sense mutation in Persian families with thiamine-responsive megaloblastic anemia. Gene 2013; 519: 295-7.

6.Bergmann AK, Sahai I, Falcone JF et al. Thiami-ne-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update. J Pediatr 2009; 155: 888-92.

7.VillaV,Rivellese A,Di Salle F,Iovine C,Poggi V,Capaldo B.Acute ischemic stroke in a young woman with the thiamine-responsive megaloblas-tic anemia syndrome.J Clin Endocrinol Me-tab2000; 85: 947-9.

8.Shaw-Smith C, Flanagan SE, Patch AM et al. Recessive SLC19A2 mutations are a cause of neo-natal diabetes mellitus in thiamine-responsive me-galoblastic anaemia. Pediatr Diabetes 2012; 13: 314-21.

9.Fullerton HJ, Wintermark M, Hills NK. Risk of recurrent arterial ischemic stroke in childhood: a prospective international study. Stroke 2016; 47: 53-9.

10.Varga EA, Sturm AC, Misita CP, Moll S. Ho-mocysteine and MTHFR mutations relation to thrombosis and coronary artery disease. Circula-tion 2005; 111: 289-93.