Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

Successful sulfonylurea treatment in a patient with permanent neonatal diabetes mellitus with a novel KCNJ11 mutation

  • Ahn, Sung Yeon (Department of Pediatrics, Ulsan University Hospital) ;
  • Kim, Gu-Hwan (Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • 투고 : 2014.06.27
  • 심사 : 2014.10.21
  • 발행 : 2015.08.10
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Permanent neonatal diabetes mellitus refers to diabetes that occurs before the age of 6 months and persists through life. It is a rare disorder affecting one in 0.2-0.5 million live births. Mutations in the gene KCNJ11, encoding the subunit Kir6.2, and ABCC8, encoding SUR1 of the ATP-sensitive potassium ($K_{ATP}$) channel, are the most common causes of permanent neonatal diabetes mellitus. Sulfonylureas close the $K_{ATP}$ channel and increase insulin secretion. KCNJ11 and ABCC8 mutations have important therapeutic implications because sulfonylurea therapy can be effective in treating patients with mutations in the potassium channel subunits. The mutation type, the presence of neurological features, and the duration of diabetes are known to be the major factors affecting the treatment outcome after switching to sulfonylurea therapy. More than 30 mutations in the KCNJ11 gene have been identified. Here, we present our experience with a patient carrying a novel p.H186D heterozygous mutation in the KCNJ11 gene who was successfully treated with oral sulfonylurea.

키워드

참고문헌

  1. Gloyn AL, Pearson ER, Antcliff JF, Proks P, Bruining GJ, Slingerland AS, et al. Activating mutations in the gene encoding the ATPsensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med 2004;350:1838-49. https://doi.org/10.1056/NEJMoa032922
  2. Vaxillaire M, Populaire C, Busiah K, Cave H, Gloyn AL, Hattersley AT, et al. Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients. Diabetes 2004;53:2719-22. https://doi.org/10.2337/diabetes.53.10.2719
  3. 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. https://doi.org/10.1056/NEJMoa061759
  4. Koster JC, Remedi MS, Dao C, Nichols CG. ATP and sulfonylurea sensitivity of mutant ATP-sensitive K+ channels in neonatal diabetes: implications for pharmacogenomic therapy. Diabetes 2005;54:2645-54. https://doi.org/10.2337/diabetes.54.9.2645
  5. 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;89:5504-7. https://doi.org/10.1210/jc.2004-1241
  6. Russo L, Iafusco D, Brescianini S, Nocerino V, Bizzarri C, Toni S, et al. Permanent diabetes during the first year of life: multiple gene screening in 54 patients. Diabetologia 2011;54:1693-701. https://doi.org/10.1007/s00125-011-2094-8
  7. Greeley SA, Naylor RN, Philipson LH, Bell GI. Neonatal diabetes: an expanding list of genes allows for improved diagnosis and treatment. Curr Diab Rep 2011;11:519-32. https://doi.org/10.1007/s11892-011-0234-7
  8. Suzuki S, Makita Y, Mukai T, Matsuo K, Ueda O, Fujieda K. Molecular basis of neonatal diabetes in Japanese patients. J Clin Endocrinol Metab 2007;92:3979-85. https://doi.org/10.1210/jc.2007-0486
  9. Gach A, Wyka K, Malecki MT, Noczynska A, Skupien J, Nazim J, et al. Islet-specific antibody seroconversion in patients with long duration of permanent neonatal diabetes caused by mutations in the KCNJ11 gene. Diabetes Care 2007;30:2080-2. https://doi.org/10.2337/dc06-2440
  10. Heo JW, Kim SW, Cho EH. Unsuccessful switch from insulin to sulfonylurea therapy in permanent neonatal diabetes mellitus due to an R201H mutation in the KCNJ11 gene: a case report. Diabetes Res Clin Pract 2013;100:e1-2. https://doi.org/10.1016/j.diabres.2013.01.016
  11. Kumaraguru J, Flanagan SE, Greeley SA, Nuboer R, Stoy J, Philipson LH, et al. Tooth discoloration in patients with neonatal diabetes after transfer onto glibenclamide: a previously unreported side effect. Diabetes Care 2009;32:1428-30. https://doi.org/10.2337/dc09-0280
  12. Tonini G, Bizzarri C, Bonfanti R, Vanelli M, Cerutti F, Faleschini E, et al. Sulfonylurea treatment outweighs insulin therapy in shortterm metabolic control of patients with permanent neonatal diabetes mellitus due to activating mutations of the KCNJ11 (KIR6.2) gene. Diabetologia 2006;49:2210-3. https://doi.org/10.1007/s00125-006-0329-x
  13. Iafusco D, Bizzarri C, Cadario F, Pesavento R, Tonini G, Tumini S, et al. No beta cell desensitisation after a median of 68 months on glibenclamide therapy in patients with KCNJ11-associated permanent neonatal diabetes. Diabetologia 2011;54:2736-8. https://doi.org/10.1007/s00125-011-2273-7
  14. Remedi MS, Agapova SE, Vyas AK, Hruz PW, Nichols CG. Acute sulfonylurea therapy at disease onset can cause permanent remission of KATP-induced diabetes. Diabetes 2011;60:2515-22. https://doi.org/10.2337/db11-0538
  15. Carmody D, Bell CD, Hwang JL, Dickens JT, Sima DI, Felipe DL, et al. Sulfonylurea treatment before genetic testing in neonatal diabetes: pros and cons. J Clin Endocrinol Metab 2014;99:E2709-14. https://doi.org/10.1210/jc.2014-2494

피인용 문헌

  1. Not All Diabetes in Infants is Type 1: A Case Report vol.7, pp.2, 2015, https://doi.org/10.1007/s13300-016-0171-1
  2. DEND Syndrome with Heterozygous KCNJ11 Mutation Successfully Treated with Sulfonylurea vol.32, pp.6, 2017, https://doi.org/10.3346/jkms.2017.32.6.1042
  3. Successful switching from insulin to sulfonylurea in a 3-month-old infant with diabetes due to p.G53D mutation in KCNJ11 vol.23, pp.3, 2015, https://doi.org/10.6065/apem.2018.23.3.154
  4. New insights into KATP channel gene mutations and neonatal diabetes mellitus vol.16, pp.7, 2015, https://doi.org/10.1038/s41574-020-0351-y
  5. Neonatal Diabetes Mellitus Due to KCNJ11 (KIR6.2) Mutation Successfully Treated with Sulfonylurea vol.28, pp.2, 2015, https://doi.org/10.5385/nm.2021.28.2.94