ESPE Abstracts

Introduction: Monogenic diabetes has been estimated to be 1 - 6% of all diabetic cases in European countries which are primarily non consanguineous populations, while the incidence in highly consanguineous areas is insufficiently defined. However, the genetic aetiology of monogenic diabetes has been shown to be widely different in areas with prevalent consanguinity compared to areas with lower rates. In this single-centre study, we aimed to evaluate the prevalence of monogenic forms of diabetes in comparison with the other types of diabetes, obtain consanguinity rate, and study the genetic background of syndromic and neonatal diabetes.

Methods: Data collection was done retrospectively at the diabetic clinic at the Dr. Jamal Ahmad Rashid Hospital in Sulaimani in the Kurdistan region of Iraq. In November 2021, there were 753 diabetic patients (376 males) up to 16 years of age registered. The age at diagnosis, type of diabetes (clinically defined), syndromic features (if any) and insulin dosage were documented from patient files. Consanguinity status was known in 734 patients. Furthermore, 11 patients with neonatal and syndromic diabetes consented to genetic testing by Next Generation Sequencing methods when offered. Selected variants were evaluated by American College of Medical Genetics standards.

Results: 268/734 patients (36%) were offspring of consanguineous families. An overwhelming majority of 716/753 (95%) patients had Type 1 diabetes (35% of them were from consanguinity) whereas only 7/753 (0.9%) had Type 2 diabetes (42% consanguineous). 13/753 (1.7%) had neonatal diabetes (54% consanguineous), 6/753 (0.8%) syndromic diabetes (100% consanguineous), and 11/753 (1.5%) clinically defined MODY (10% consanguineous). The genetic cause was elucidated thus far in 4/6 syndromic diabetes patients (homozygous variants in INSR, SLC29A3, WFS1 [2x]) and in 5/11 neonatal diabetes patients (de novo heterozygous variants in ABCC8, INS and homozygous variants in GLIS3 [2x], PTF1A). 5 variants are novel.

Conclusion: This single center study confirms that even in a highly consanguineous population, type 1 diabetes represents the prevailing paediatric diabetes subtype, and that syndromic diabetes arises predominantly from consanguinity. More extensive studies would be required to calculate a precise incidence of diabetes subtypes in this population.