The personalized approach to neonatal diabetes therapy depending on the genetic defect

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Abstract


Neonatal diabetes mellitus (NDM) is defined as a heterogeneous group of genetic disorders with onset before 6 months of age. Mutations in KATP channel genes (KCNJ11, ABCC8) and the insulin gene (INS) are the most common causes of NDM. Accurate molecular diagnosis of NDM has significant clinical importance as it may influence diabetes treatment, explain pleiotropic features and define the prognosis in the examined subject as well as in other family members .

In this report we present the results of a genetic examination of 70 patients with NDM, generalized the experience of using sulfonylurea in patients with KCNJ11 and ABCC8 genes mutations for the period from 2009 to 2016. A correlation is shown between the type of mutation, the course of the disease, and the sensitivity of patients to glibenclamide.


Yulia V. Tikhonovich

Endocrinology Research Centre

Author for correspondence.
Email: sunflower25@mail.ru
ORCID iD: 0000-0001-7747-6873
SPIN-code: 6492-6790

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Natalia A. Zubkova

Endocrinology Research Centre

Email: zunata2006@yandex.ru
ORCID iD: 0000-0002-1346-7545
SPIN-code: 5064-9992

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Anatoly N. Tiulpakov

Endocrinology Research Centre

Email: ant@endocrincentr.ru
ORCID iD: 0000-0001-8500-4841
SPIN-code: 8396-1798

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

  1. Iafusco D, Stazi MA, Cotichini R, et al. Permanent diabetes mellitus in the first year of life. Diabetologia. 2002;45(6):798-804. doi: 10.1007/s00125-002-0837-2.
  2. Rubio-Cabezas O, Klupa T, Malecki MT, Consortium C. Permanent neonatal diabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants. Eur J Clin Invest. 2011;41(3):323-333. doi: 10.1111/j.1365-2362.2010.02409.x.
  3. Fosel S. Transient and permanent neonatal diabetes. Eur J Pediatr. 1995;154(12):944-948.
  4. Flanagan SE, Patch AM, Mackay DJ, et al. Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes. 2007;56(7):1930-1937. doi: 10.2337/db07-0043.
  5. Gloyn AL, Pearson ER, Antcliff JF, et al. 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):1838-1849. doi: 10.1056/NEJMoa032922.
  6. Flanagan SE, Edghill EL, Gloyn AL, et al. Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype. Diabetologia. 2006;49(6):1190-1197. doi: 10.1007/s00125-006-0246-z.
  7. Stoy J, Edghill EL, Flanagan SE, et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007;104(38):15040-15044. doi: 10.1073/pnas.0707291104.
  8. Proks P, Antcliff JF, Lippiat J, et al. Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features. Proc Natl Acad Sci U S A. 2004;101(50):17539-17544. doi: 10.1073/pnas.0404756101.
  9. Proks P, Arnold AL, Bruining J, et al. A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Hum Mol Genet. 2006;15(11):1793-1800. doi: 10.1093/hmg/ddl101.
  10. Pearson ER, Flechtner I, Njolstad PR, et al. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006;355(5):467-477. doi: 10.1056/NEJMoa061759.
  11. Rafiq M, Flanagan SE, Patch AM, et al. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008;31(2):204-209. doi: 10.2337/dc07-1785.
  12. Zwaveling-Soonawala N, Hagebeuk EE, Slingerland AS, et al. Successful transfer to sulfonylurea therapy in an infant with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome and a novel ABCC8 gene mutation. Diabetologia. 2011;54(2):469-471. doi: 10.1007/s00125-010-1981-8.

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Copyright (c) 2017 Tikhonovich Y.V., Zubkova N.A., Tiulpakov A.N.

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