ESPE2016 Rapid Free Communications Pathophysiology of Disorders of Insulin Secretion (8 abstracts)
Background: Monogenic diabetes represents a 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 according to age of onset, with neonatal DM (<6 months of age) and maturity onset diabetes of young (MODY) (>6 months and <25 years of age); not every case can be classified into those groups.
Objective and hypotheses: We aim to evaluate non-MODY monogenic diabetes diagnosed in our clinic, and emphasize the characteristics of patients.
Method: We evaluated the patients with monogenic diabetes, during the last 10 years period. Type 1 DM, MODY, and patients with negative autoantibodies and no mutation were excluded from the study.
Results: Twelve patients, aged 1 days to 11 years, were diagnosed with non-MODY monogenic diabetes. Half the patients were diagnosed after 6 months of age. Most patients had a KATP channel defect. Disruption of beta cells was detected in 6 patients, with 3 cases having a WFS1 mutation, 3 had positive autoantibodies (2 an LRBA mutation, and one CD25 deficiency). Additional systemic findings including severe immune system dysfunction were seen in 6/12 patients (Table). Treatment with sulphonylurea was succesful in two patients with an ABCC8 gene mutation. The other patients were given insulin in very heterogenous doses (0.41.6 U/Kg body weight). Four patients died during follow-up, three of which had immune dysfunction.
Conclusion: Monogenic diabetes due to a mutation in a non-MODY gene can be diagnosed after 6 months of age. Even with positive autoantibodies. Immune dysfunction was present in 50% of patients 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.
10 Sep 2016 - 12 Sep 2016