Esra BASKIN, Kaan GÜLLEROĞLU, Özlem AYDOĞ, Sare GÜLFEM AKYÜZ, Namık YAŞAR ÖZBEK

Tromboza Eğilimin Eşlik Ettiği Wolfram Sendromu

Wolfram sendromu; diabetes mellitus, optik atrofiye diabetes insipitus ve işitme kaybının eklenmesiyle karakterize, otozomal resesif kalıtım gösteren bir hastalıktır. Wolfram sendromunda kanamaya eğilim bildirilmiş olmakla beraber tromboza yatkınlık ile ilgili bir bilgi mevcut değildir. Wolfram sendromu tanısıyla takipli tekrarlayan tromboz atakları olan iki kız kardeş sunulmuştur. Wolfram sendromu olan iki kız kardeş (13 ve 12 yaşlarında) her seferinde trombozla sonuçlanan venovenöz fistül açma girişimleri sonrası kliniğimize yönlendirilmişlerdi. Hastaların tromboza eğilim yönünden tetkikleri yapıldı. Anti-trombin III, protein C ve S, lipoprotein (a), lupus antikoagülanı, antikardiyolipin IgG ve IgM düzeyleri normal sınırlardaydı. Genetik incelemede faktör V Leiden 1691 G>A ve faktör II (protrombin) 20210 G>A her iki hastada da homozigot normal, MTHFR C677T ise her iki hastada da heterozigot idi. Yeterli heparinizasyon sağlandıktan sonra herhangi bir tromboz atağı gözlenmedi. Daha önce Wolfram sendromu ve tromboza eğilim birlikteliği bildirilmemiştir. Tromboza eğilim çoklu fenotipi olan bir genetik hastalık olan Wolfram sendromunun yeni bir bulgusu olabilir.

Anahtar Kelimeler:

Kronik böbrek yetmezliği, Tromboz, Wolfram sendromu

Wolfram Syndrome Accompanied by Predisposition to Thrombosis

Wolfram syndrome is a genetic condition, which is inherited in autosomal recessive form and characterized by the combination of diabetes mellitus, optic atrophy, diabetes insipidus and deafness. Bleeding tendency in Wolfram syndrome was noted but a predisposition to thrombosis has not been reported previously. We present two siblings with Wolfram syndrome and recurrent thrombosis. Two girls (13 and 12 years old) with Wolfram syndrome were referred to our clinic because of recurrent thrombotic attacks after each attempt to open venovenous fi stulas. Tests were performed to determine the patients’ predisposition to thrombosis. Anti-thrombin III, protein C and S, lipoprotein (a), lupus anticoagulant, anticardiolipin IgG and IgM were within the normal range. Genetic analysis showed that factor V Leiden 1691 G>A and factor II (prothrombin) 20210 G>A were homozygous normal and MTHFR C677T gene mutation was heterozygous for each patient. No thrombosis attack was observed after adequate heparinization. Predisposition to thrombosis is a newly feature in Wolfram syndrome, as thrombosis with this syndrome has never been reported

Keywords:

Chronic renal failure, Thrombosis, Wolfram syndrome,

PDF

___

Hatipoğlu H, Hatipoğlu MG, Kansu Ö. A case with Wolfram (DIDMOAD) syndrome and oral fi ndings (a case report). Dumlupınar Üniversitesi Fen Bilimleri Enstitüsü Dergisi 2007;14: 135-40.
Viswanathan V, Medempudi S, Kadiri M. Wolfram syndrome. JAPI 2008; 56: 197-9.
Al-Sheyyah M, Jarrah N, Younis E, Shennak MM, Hadidi A, Awidi A, et al. Bleeding tendency in Wolfram syndrome: A newly identifi ed feature with phenotype genotype correlation. Eur J Pediatr 2001; 160: 243-6.
Wolfram DJ, Wagener HP. Diabetes mellitus and simple optic atrophy among siblings: Report of four cases. Mayo Clin Proc 1938; 9: 715-8.
Barrett TG, Bundey SE. Wolfram (DIDMOAD) syndrome. J Med Genet 1997; 34: 838-41.
El-Shanti H, Lidral AC, Jarrah N, Druhan L, Ajlouni K. Homozygosity mapping identifi es an additional locus for Wolfram syndrome on chromosome 4q. Am J Hum Genet 2000; 66:1229-36.
Hofmann S, Philbrook C, Gerbitz KD, Bauer MF. Wolfram syndrome: Structural and functional analyses of mutant and wild- type wolframin, the WFS1 gene product. Hum Mol Genet 2003; 12:2003-12.
Fonseca SG, Ishigaki S, Oslowski CM, Lu S, Lipson KL, Ghosh R, et al. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest 2010;120:744- 55.
Manaviat MR, Rashidi M, Mohammadi SM. Wolfram syndrome presenting with optic atrophy and diabetes mellitus: Two case reports. Cases Journal 2009; 2: 9355-7.
Kinsley BT, Swift M, Dumont RH, Swift RG. Morbidity and mortality in the Wolfram syndrome. Diabetes Care 1995;18:1566-70.
Ito S, Sakakibara R, Hattori T. Wolfram syndrome presenting marked brain MR imaging abnormalities with few neurologic abnormalities. Am J Neuroradiol 2007; 28:305-6.
Genis D, Dávalos A, Molins A, Ferrer I. Wolfram syndrome: A neuropathological study. Acta Neuropathol 1997;93:426-9.
Bespalova IN, Camp GV, Bom SJH, Brown DJ, Cryns K, DeWan AT, et al. Mutations in the Wolfram syndrome 1 gene (WFS1) are a common cause of low frequency sensorineural hearing loss. Human Mol Genet 2001;10:2501-8.
Casserly LF, Dember LM. Thrombosis in end-stage renal disease. Semin Dial 2003;16:245-56.
Fleischer LM, Wilson TA, Parker MM. Hypernatremic dehydratation, diabetes insipidus, and cerebral venous sinus thrombosis in a neonate: A case report. J Med Case Rep 2007;1:66-9.
Piazza G, Goldhaber SZ, Kroll A, Goldberg RJ, Emery C, Spencer FA. Venous thromboembolism in patients with diabetes mellitus. Am J Med 2012; 125:709-16.
Alluri RV, Mohan V, Komandur S, Chawda K, Chaudhuri JR, Hasan Q. MTHFR C677T gene mutation as a risk factor for arterial stroke: A hospital based study. Eur J Neurol 2005;12:40-4.
Ding Q, Quyang Q, Xi X, Wang X, Shen Y, Wang H. Maternal chromosome 4 heterodisomy/isodisomy and B βchain Trp323X mutation resulting in severe hypodysfi brinogenaemia. Thromb Haemost 2012; 108:589-800.