Transient neonatal diabetes mellitus caused by a novel mutation in the ABCC8 gene

Abstract

Neonatal diabetes mellitus is a rare monogenic form of diabetes that develops in the first 6 months of life. Neonatal diabetes mellitus is commonly divided in two groups as transient and permanent. Genetic and epigenetic anomalies of chromosome 6q24 locus are responsible for 70% of transient neonatal diabetes mellitus cases. Incidence of macroglossia, umbilical hernia, cardiac and renal anomalies is increased in transient neonatal diabetes mellitus patients. Mutations in the genes (ABCC8 and KCNJ11) encoding two protein subunits (SUR1 and Kir6.2) of ATP-sensitive potassium channels constitute the second common cause of transient neonatal diabetes mellitus. In this article, we present a case with homozygous missense mutation (DNA expression: c1456> T), which was found in the ABCC8 gene in a 3.5-month-old patient with no congenital anomalies, leading to transient neonatal diabetes mellitus.

Keywords

• ATP-sensitive potassium channel,Neonatal diabetes,ABCC8 gene

ABCC8 geninde yeni bir mutasyonun neden olduğu geçici neonatal diyabet

Abstract

Neonatal diyabet, yaşamın ilk altı ayında ortaya çıkan ve diyabetin nadir görülen monojenik bir formudur. Genel olarak geçici ve kalıcı diye iki gruba ayrılır. Geçici neonatal diyabetli olguların %70’inden kromozom 6q24 lokusun genetik ve epigenetik anomaliler sorumludur. Bu olgularda makroglossi, umlikal herni, kardiyak ve renal anomali sıklığı artmıştır. ATP duyarlı potasyum kanallarının iki protein alt birimini (SUR1 ve Kir6.2) kodlayan genlerdeki (ABCC8 ve KCNJ11) mutasyonlar geçici neonatal diyabetin ikinci sık nedenini oluşturmaktadır. Bu yazıda konjenital anomalilerin eşlik etmediği, 3.5 aylık bir hastada ABCC8 geninde yeni saptanan ve geçici neonatal diyabete yol açan homozigot missense mutasyonlu (DNA tanımlaması: c1456>T) bir olgu sunulmuştur.

Keywords

• Neonatal diabet,ATP duyarlı K kanalı,ABCC8 geni

References

1. 1. Von Muhlendahl KE, Herkenhoff H. Long-term course of neonatal diabetes. N Engl J Med.1995;333:704–8.
2. 2. Sperling MA. ATP-sensitive potassium channels: neonatal diabetes mellitus and beyond. N Engl J Med. 2006;355:507–10.
3. 3. Murphy R, Ellard S, & Hattersley AT. Clinical implications of a molecular genetic classification of monogenic B-cell diabetes. Nat Clin Pract Endocriol Metab. 2008;4:200–13.
4. 4. Temple IK, Gardner RJ, Mackay DJ, Barber JC, Robinson DO, Shield JP. Transient neonatal diabetes mellitus: widening our understanding of the aetiopathogenesis of diabetes. Diabetes. 2000;49:1359–66.
5. 5. Docherty LE, Kabwama S, Lehmann A, Hawke E, Harrison L, Flanagan SE, et al. Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients. Diabetologia. 2013;56:758–62.
6. 6. Sperling MA. Neonatal Diabetes Mellitus. In: Sperling MA (ed). Pediatric Endocrinology. Elsevıer Saunders, Philadelphia. 2014;pp.277-90.
7. 7. Hattersley A, Bruining J, Shield J, Njolstad P, Donaghue KC. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes. 2009;12:33–42.
8. 8. Pearson ER, Flechtner I, Njolstad PR, Malecki MT, Flanagan SE, Larkin B, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006;355:467–77.