ESPE2016 Free Communications Management of Disorders of Insulin Secretion (6 abstracts)
DPP-4 Inhibitor is an Alternative Effective Treatment in a Common Cause of Anti-GAD Negative “Type 1 Diabetes” - A Founder CISD2 Mutation
Ulla Najwa Abdulhag a , Ariella Weinberg-Shukron b , Maha Atwan Abdelhadi a , Gil Leibovitz a , Ephrat Levy-Lahad b , Adi Aurbach a , Eran Lavi a , Muntaser Abassi a , Michael Wilchansky a , Abdelsalam Abu Libdeh a & David Zangen a
aHadassah Hebrew University Medical Center, Jerusalem, Israel; bShaare Zedek Medical Center, Jerusalem, Israel
Background: Wolfram syndrome type 2 (WFS2) characterized by childhood GI ulcers/ bleeding, diabetes, and neurodegeneration with optic atrophy and hearing loss was recently elucidated as caused by CISD2/NAF-1 gene mutation. NAF-1 suppression in cells results in intra-mitochondrial accumulation of iron, increased ROS generation and consequently increased cellular apoptosis. So far only two mutations in four families were reported.
Objective: Elucidate the clinical and the molecular genetic characteristics of anti-Gad negative “type 1 diabetes” in patients from seven unrelated Palestinian consanguineous families.
Patients and methods: About 13 patients from seven different families were treated with insulin following juvenile onset diabetes. The finding of negative anti-GAD antibodies together with personal or sibling history of pediatric upper GI bleeding/ulcer lead into further investigation of mild (ignored) visual/acoustic symptoms. Consequently we sequenced the CISD2 gene and offered a therapeutic trial with DPP-4 inhibitor.
Results: The homozygous IVS1+6G>C, p.E37Q CISD2 gene mutation resulting in skipping of the 2nd out of three exons of the CISD2 gene was identified in all of the cohort patients. Studying eight microsatellite markers flanking the CISD2 gene indicated a founder effect in at least six unrelated families. Restriction enzyme analysis of 200 healthy control alleles showed a surprising high carrier rate of 1/40-2.5%. Given the known protective effect of GLP-1 against ER stress-mediated cell death, using an agent combining Metformin and the DPP-4 inhibitor Sitagliptin enabled successful weaning from insulin while achieving a good glycemic control in our 2 first patients.
Conclusion: Early manifestation of GI symptoms in anti-GAD negative “type 1 diabetes” should lead to suspect the relatively common diagnosis of WFS2 caused by a founder CISD2 mutation. Insulin may be switched to incretin based oral therapy. Further mechanistic studies with direct therapeutic consequences are underway to enable a definitive and effective therapy for the degenerative pathophysiology in WFS2.
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more