Importance of genetic testing in neonatal diabetes and use of sulphonylureaImportance of genetic testing in neonatal diabetes and use of sulphonylurea
American Journal of Biomedical and Life Sciences
Volume 3, Issue 4, August 2015, Pages: 84-86
Received: Apr. 12, 2014;
Accepted: Jul. 28, 2014;
Published: Jul. 9, 2015
Views 3167 Downloads 60
Eman Ahmad Alsafi, Department of Pediatrics, Elsafi, Al-Agha and Ahmad, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia
Ihab Abdulhamed Ahmad, Department of Pediatrics, Elsafi, Al-Agha and Ahmad, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia; Department of Pediatrics, Ahmad, Zagazig university Hospital, Egypte
Abdulmoein Eid AL-Agha, Department of Pediatrics, Elsafi, Al-Agha and Ahmad, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia
Patients with permanent neonatal diabetes usually present within the first three months of life and need insulin treatment. In most, the cause is unknown. Because ATP-sensitive potassium (KATP) channels mediate glucose-stimulated insulin secretion from the pancreatic beta cells, activating mutations in the gene encoding the Kir6.2 subunit of this channel (KCNJ11) cause neonatal diabetes. Genotyping identifies the exact molecular etiology of early onset insulin requiring diabetes and has the potential to alter the management of the patient, who would otherwise be insulin dependent for life. Method: We identified a 6 year-old child who presented at 3 months of age with diabetic ketoacidosis. Blood samples for molecular genetic analysis were done. Results: The patient was diagnosed as a heterozygous for a missense mutation in the (KCNJ11) gene, for which she switched to sulphonylurea with a dose of 0.05 mg/kg/day. Conclusion: the need for medical practitioners to consider molecular testing for all patients who present with diabetes below 6 months of age as this will facilitate accurate diagnosis and appropriate therapy.
Eman Ahmad Alsafi,
Ihab Abdulhamed Ahmad,
Abdulmoein Eid AL-Agha,
Importance of genetic testing in neonatal diabetes and use of sulphonylureaImportance of genetic testing in neonatal diabetes and use of sulphonylurea, American Journal of Biomedical and Life Sciences.
Vol. 3, No. 4,
2015, pp. 84-86.
Karl Ernst von Mühlendah, M.D., and Heiner Herkenhoff, M.D. Long-Term Course of Neonatal Diabetes .N Engl J Med 1995; 333:704-708 DOI: 10.1056/NEJM199509143331105
Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, Howard N, Srinivasan S, Silva JM, Molnes J, Edghill EL, Frayling TM, Temple IK, Mackay D, Shield JP, Sumnik Z, van Rhijn A, Wales JK, Clark P, Gorman S, Aisenberg J, Ellard S, Njølstad PR, Ashcroft FM, Hattersley AT. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004;350(18):1838.
Gloyn AL, Cummings EA, Edghill EL, Harries LW, Scott R, Costa T, Temple IK, Hattersley AT, Ellard S. Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel. J Clin Endocrinol Metab. 2004;89(8):3932
Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Søvik O, Polak M, Hattersley AT, Neonatal Diabetes International Collaborative Group . Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations.N Engl J Med. 2006;355(5):467.
Landau Z, Wainstein J, Hanukoglu A, Tuval M, Lavie J, Glaser B. Sulfonylurea-responsive diabetes in childhood. J Pediatr. 2007;150(5):553
Zung A, Glaser B, Nimri R, Zadik Z. Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2 . J Clin Endocrinol Metab. 2004 Nov;89(11):5504-7
Hattersley AT, Ashcroft FM. Activating mutations in Kir6.2 and neonatal diabetes: new clinical syndromes, new scientific insights, and new therapy. Diabetes, VOL. 54, september 2005. ADA.
Anna L. Gloyn, D.Phil., Ewan R. Pearson, M.R.C.P., Jennifer F. Antcliff, B.Sc., Peter Proks, D.Phil., G. Jan Bruining, M.D., Annabelle S. Slingerland, M.D., Neville Howard, M.D., F.R.A.C.P., Shubha Srinivasan, M.B., B.S., M.R.C.P., José M.C.L. Silva, M.D., Janne Molnes, M.Sc., Emma L. Edghill, M.Sc., Timothy M. Frayling, Ph.D., I. Karen Temple, F.R.C.P., Deborah Mackay, Ph.D., Julian P.H. Shield, M.D., F.R.C.P.C.H., Zdenek Sumnik, M.D., Adrian van Rhijn, M.D., Jerry K.H. Wales, D.M., F.R.C.P.C.H., Penelope Clark, Ph.D., F. R. C. Path., Shaun Gorman, M.R.C.P., Javier Aisenberg, M.D., Sian Ellard, Ph.D., M. R. C. Path., Pål R. Njølstad, M.D., Ph.D., Frances M. Ashcroft, Ph.D.,
and Andrew T. Hattersley, D.M., F.R.C.P. Activating Mutations in the Gene Encoding the ATP-Sensitive Potassium-Channel Subunit Kir6.2 and Permanent Neonatal Diabetes .N Engl J Med 2004;350:1838-49.
Rica I, Luuriaga C, Peres de Nanclares G, Estalella I, Aragones A, et al.The majority of cases of neonatal diabetes in Spain can be explained by known genetic abnormalities. DIABETIC Medicine 2007; 24:707-13.
10.Slingerland AS, Nuboer R, Hadders-Algra M et al (2006) Improved motor development and good longterm glycaemic control with sulfonylurea treatment in a patient with the syndrome of intermediate developmental delay, early-onset generalised epilepsy and neonatal diabetes associated with the V59M mutation in the KCNJ11 gene. Diabetologia 49: 2559–63
Edghill et al, Insulin Mutation Screening in 1,044 Patients With Diabetes .Mutations in the INS Gene Are a Common Cause of Neonatal Diabetes but a Rare Cause of Diabetes Diagnosed in Childhood or Adulthood. DIABETES, VOL. 57, APRIL 2008
Sagen JV, Ræder H, Hathout E et al (2004) Permanent neonatal diabetes due to mutation in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes 53: 2713–18