Exp Clin Endocrinol Diabetes 2018; 126(10): 612-618
DOI: 10.1055/s-0043-120571
Article
© Georg Thieme Verlag KG Stuttgart · New York

Monogenic Diabetes Not Caused By Mutations in Mody Genes: A Very Heterogenous Group of Diabetes

Zeynep Şıklar
1   Department of Pediatric Endocrinology, Ankara University School of Medicine, Ankara, Turkey
,
Elisa de Franco
2   Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
,
Matthew B. Johnson
2   Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
,
Sarah E. Flanagan
2   Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
,
Sian Ellard
2   Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK
,
Serdar Ceylaner
3   Intergen Genetics Center, Ankara, Turkey
,
Kaan Boztuğ
4   CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
,
Figen Doğu
5   Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey
,
Aydan İkincioğulları
5   Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey
,
Zarife Kuloğlu
6   Department of Pediatric Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
,
Aydan Kansu
6   Department of Pediatric Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
,
Merih Berberoğlu
1   Department of Pediatric Endocrinology, Ankara University School of Medicine, Ankara, Turkey
› Author Affiliations
Further Information

Publication History

received 17 July 2017
revised28 September 2017

accepted 29 September 2017

Publication Date:
28 November 2017 (online)

Abstract

Monogenic diabetes represents a heterogeneous group of disorders resulting from a single gene defect leading to disruption of insulin secretion or a reduction in the number of beta cells. Despite the classification of monogenic diabetes into neonatal diabetes or maturity onset diabetes of the young (MODY) according to age of onset, not every case can be classified into those 2 groups. We evaluated patients with monogenic diabetes diagnosed during the last 10 year period. Type 1 DM, MODY, and patients with negative autoantibodies and no mutation in a known gene were excluded from the study. Thirteen patients were diagnosed with monogenic diabetes in Department of Pediatric Endocrinology, Ankara University School of Medicine, Ankara, Turkey. Five of them were diagnosed after 6 months of age. Five had a KATP channel defect. Mutations in genes resulting in destruction of beta cells were detected in 7 patients, with 4 cases having a WFS, 2 an LRBA, and one a IL2RA mutation. Additional systemic findings were seen in 6/13 patients, with 5/6 having severe immune system dysfunction. Treatment with sulphonylurea was successful in two patients.. The other patients were given insulin in differing doses. Four patients died during follow-up, three of which had immune system dysfunction. Monogenic diabetes can be diagnosed after 6 months of age, even with positive autoantibodies. Immune dysfunction was a common feature in our cohort and should be investigated in all patients with early-onset monogenic diabetes. Mortality of patients with monogenic diabetes and additional autoimmunity was high in our cohort and is likely to reflect the multisystem nature of these diseases.