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Endocrine Abstracts (2020) 71 030 | DOI: 10.1530/endoabs.71.030

BES2020 BES 2020 A rare ABCC8 gene mutation causing severe Maturity-Onset Diabetes of the Young (MODY-12): case report and mini review (1 abstracts)

A rare ABCC8 gene mutation causing severe Maturity-Onset Diabetes of the Young (MODY-12): case report and mini review

Timmers Marijke 1 , Dirinck Eveline 1, , Lauwers Patrick 2 & De Block Christophe 1,


1Department of Endocrinology, Diabetology & Metabolism, Antwerp University Hospital, Edegem, Belgium; 2Department of Vascular Surgery, Antwerp University Hospital, Edegem, Belgium; 3Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium

Context: Maturity-Onset Diabetes of the Young (MODY) refers to a group of monogenic β cell disorders1. MODY12 comprises various mutations in the ATP-binding cassette transporter subfamily C member 8 (ABCC8) gene of the ATP-sensitive potassium (K-) channel and is a condition that is not frequently encountered, comprising 1% of all MODY types1. Gain-of-function ABCC8 mutations can result in neonatal diabetes mellitus and/or MODY12, whereas loss-of-function mutations can cause neonatal hyperinsulinism and hypoglycemia1. Moreover, the possibility of an overlap and development of MODY12 in patients with congenital hyperinsulinism has been reported1.

Case description and evidence acquisition: Here we present a case of a 35-year old woman with a severe disease course (with all diabetic microvascular complications and presentation with a Charcot arthropathy) and a rare mutation in the ABCC8 gene. We provide a review of all published cases of MODY12 between 2018 and June 15th 2020 by conducting a structured search for “ABCC8”, “Maturity-Onset Diabetes of the Young”, “MODY”, “MODY12” and “Charcot” on Pubmed and including relevant case reports, case series and genetic articles describing case outcomes.

Evidence synthesis: We included 54 subjects with 39 different ABCC8 mutations. To the best of our knowledge, the c.3544C>T p.(Arg1182Trp) variant seen in our patient, has only been reported once before in 2014 in a patient having neonatal diabetes mellitus (2). MODY12 includes a heterogeneous spectrum of diseases with age at onset varying between a few weeks – 42 year old, HbA1c at diagnosis ranging between 5.6–13.7% (38 mmol/mol–126 mmol/mol). Complications have often not been reported in MODY12 cases, but – when documented – the clinical heterogeneity (phenotype and complication rate) appeared large, in part explained by the type and location of the mutation3.

However, different phenotypes can be seen within relatives with the same mutation, as documented in several cases3 and also illustrated by our case. To the best of our knowledge up till now no Charcot arthropathy has been described in MODY12. Overall, in 17% of subjects a sulphonylureum (SU) was started after genetic diagnosis. In 15% of subjects this led to a cessation of insulin; in one other case the dose of insulin could be reduced. Evidence suggests that in patients with an inactivating mutation incretin-based therapy is superior4,5.

Conclusions: Meticulous documentation of the disease course, complications and response to therapy is necessary to improve our insight and management of the heterogeneous disease that MODY12 comprises. We also conclude that considering the diagnosis of MODY and demanding genetic testing in certain patients can be of importance, as it can guide therapeutic decisions.

References: 1. Reilly F, Sanchez-Lechuga B, Clinton S, Crowe G, Burke M, Ng N, et al. Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy. Diabet Med. 2019.

2. Bonnefond A, Philippe J, Durand E, Muller J, Saeed S, Arslan M, et al. Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through one-step PCR-based enrichment in combination with next-generation sequencing. Diabetes Care. 2014;37(2):460–7.

3. Riveline JP, Rousseau E, Reznik Y, Fetita S, Philippe J, Dechaume A, et al. Clinical and metabolic features of adult-onset diabetes caused by ABCC8 mutations. Diabetes Care. 2012;35(2):248–51.

4. Matsutani N, Furuta H, Matsuno S, Oku Y, Morita S, Uraki S, et al. Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young-onset diabetes with exome sequencing. J Diabetes Investig. 2020;11(2):333–6.

5. Karatojima M, Furuta H, Matsutani N, Matsuno S, Tamai M, Komiya K, et al. A family in which people with a heterozygous ABCC8 gene mutation (p.Lys1385Gln) have progressed from hyperinsulinemic hypoglycemia to hyperglycemia. J Diabetes. 2020;12(1):21–4.

Volume 71

Belgian Endocrine Society 2020

Online, Online
11 Nov 2020 - 11 Nov 2020

Belgian Endocrine Society 

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