Diabetes mellitus in beckwith-wiedemann syndrome: an unusual co-occurence

Yesmine Elloumi; Abbes Wissal; Frikha Hamdi; Maalej Souhir; Dhoha Ben Salah; Boujelben Khouloud; Faten Hadj Kacem; Mnif Fatma; Nadia Charfi; Mnif Mouna; Elleuch Mouna; Mohamed Abid; Majdoub Nabila Rekik

doi:10.1530/endoabs.99.EP130

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Endocrine Abstracts (2024) 99 EP130 | DOI: 10.1530/endoabs.99.EP130

ECE2024 Eposter Presentations Diabetes, Obesity, Metabolism and Nutrition (383 abstracts)

Diabetes mellitus in beckwith-wiedemann syndrome: an unusual co-occurence

Yesmine Elloumi , Abbes Wissal , Frikha Hamdi , Maalej Souhir , Ben Salah Dhoha , Boujelben Khouloud , Hadj Kacem Faten , Mnif Fatma , Nadia Charfi , Mnif Mouna , Elleuch Mouna , Mohamed Abid & Nabila Rekik Majdoub

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Hospital of Hedi Chaker

Background: Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformation(s). Diabetes mellitus is not characteristic of BWS. If anything, BWS is associated with hypoglycaemia which is believed to be related to hyperinsulinaemia due to an unknown mechanism. The presentation of concurrent BWS and permanent diabetes mellitus (DM) is uncommun.

Case Report: We report the case of a two year old girl with a past medical history of BWS. She was a term baby. She had earlobe crease, macroglossia and omphalocoele requiring immediate surgical repair. Genetic testing detected a decreased methylation intensity of the KvDMR1 (differentially methylated region) in the chromosome region 11p15.5, consistent with a diagnosis of BWS. Paternal uniparental isodisomy of 11p15 was unlikely but couldn’t be excluded and her DNA methylation was normal at H19. At the age of two, she presented to her primary care physician with weight loss, polyuria, and polydipsia. She was diagnosed with new-onset diabetes and was started on a basal-bolus insulin regimen. At ten years old, she consulted with a poorly controlled DM. Lab results showed negative testing for the autoantibodies against Glutamic Acid Decarboxylase (GADA), insulinoma antigen-2 (IA-2A) and islet cells (ICA). Insulin blood level and c peptid level were respectively < 7 pmol/l and < 0,03 μg/l for a concomitant blood sugar at 5,13 g/l. We can postulate as a mechanism for such paradoxal association, a loss of imprinting control region (IC2) methylation that regulates the expression of CDKN1C which has been previously reported to be associated with permament diabetes, as reported in 2023. A loss of methylation in imprinted PLAG1 locus on chromosomes 6q24 responsible for transient neonatal diabetes mellitus (TNDM) is the second hypothesis but it was described to be associated with transient DM as reported in 2015.

Conclusion: Our case illustrates the second case in the literature associating paradoxal permanent DM and BWS. Further biomolecular investigations are required to identify the possible interactions between BWS and glucose homeostasic abnormality.