Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family

Eleni Z Giannopoulou; Olga Ovcarov; Elisa De Franco; Fabian Kassberger; Susanne Nusser; Marie Celine Otto; Christian Denzer; Martin Wabitsch

doi:10.1515/jpem-2020-0462

Article

Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family

Eleni Z Giannopoulou , Olga Ovcarov , Elisa De Franco , Fabian Kassberger , Susanne Nusser , Marie Celine Otto , Christian Denzer and Martin Wabitsch

Published/Copyright: November 13, 2020

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information Explore this Subject

From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 2

Abstract

Objectives

Neonatal diabetes mellitus (NDM) is a rare monogenic diabetes form, occurring mainly from ATP-binding cassette subfamily C member 8 (ABCC8) and KCNJ11 mutations. ABCC8 mutations have also been found to cause adult-onset diabetes. What is new?: •Novel ABCC8 mutation in an NDM case •Heterogeneous clinical presentation of diabetes and response to sulfonylurea therapy among family members with the same ABCC8 mutation.

Case presentation

We report the case of a newborn with NDM and a heterozygous ABCC8 novel variant (c.3835G>A), successfully treated with sulfonylurea. The same ABCC8 variant was found in two other family members, already treated for type 2 diabetes.

Conclusions

This case demonstrates the variable phenotypic presentation of diabetes due to a novel ABCC8 mutation (c.3835G>A), ranging from transient NDM to adult-onset, insulin-demanding diabetes, among family members. Genetic testing in young individuals with a strong family history of diabetes, presenting with non-autoimmune diabetes is recommended as it can determine prognosis and treatment of affected family members.

Keywords: monogenic diabetes; sulfonylurea; case report

Corresponding author: Dr. Martin Wabitsch, Prof., Department of Pediatrics and Adolescent Medicine, Division of Pediatric Endocrinology and Diabetes, Ulm University, Eythstr. 24, 89075, Ulm, Germany, E-mail: Martin.Wabitsch@uniklinik-ulm.de

Research funding: None declared.
Author contributions: EZG, OO, FK, SN, MCO, CD and MW collected clinical data. EZG and MW designed the study, analyzed data and drafted the article. EDF performed genetic sequencing and contributed to the interpretation of data. All authors revised the article and approved the final version to be submitted.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the authors’ Institutional Review Board or equivalent committee.

References

1. De Franco, E, Flanagan, SE, Houghton, JA, Lango Allen, H, Mackay, DJ, Temple, IK, et al.. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet 2015;386:957–63. https://doi.org/10.1016/s0140-6736(15)60098-8.Search in Google Scholar

2. Bowman, P, Flanagan, SE, Edghill, EL, Damhuis, A, Shepherd, MH, Paisey, R, et al.. Heterozygous ABCC8 mutations are a cause of MODY. Diabetologia 2012;55:123–7. https://doi.org/10.1007/s00125-011-2319-x.Search in Google Scholar PubMed

3. Zhang, M, Chen, X, Shen, S, Li, T, Chen, L, Hu, M, et al.. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds. J Pediatr Endocrinol Metab 2015;28:877–84. https://doi.org/10.1515/jpem-2014-0429.Search in Google Scholar PubMed

4. Garcin, L, Mericq, V, Fauret-Amsellem, AL, Cave, H, Polak, M, Beltrand, J. Neonatal diabetes due to potassium channel mutation: response to sulfonylurea according to the genotype. Pediatr Diabetes 2020;21:932–41. https://doi.org/10.1111/pedi.13041.Search in Google Scholar PubMed

5. Hattersley, A, Bruining, J, Shield, J, Njolstad, P, Donaghue, K. ISPAD Clinical Practice Consensus Guidelines 2006–2007. The diagnosis and management of monogenic diabetes in children. Pediatr Diabetes 2006;7:352–60. https://doi.org/10.1111/j.1399-5448.2006.00217.x.Search in Google Scholar PubMed

6. 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;35:248–51. https://doi.org/10.2337/dc11-1469.Search in Google Scholar PubMed PubMed Central

7. Thomas, PM, Cote, GJ, Wohllk, N, Haddad, B, Mathew, PM, Rabl, W, et al.. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995;268:426–9. https://doi.org/10.1126/science.7716548.Search in Google Scholar PubMed

8. Shima, KR, Usuda, R, Futatani, T, Akahori, H, Kaneko, S, Yorifuji, T, et al.. Heterogeneous nature of diabetes in a family with a gain-of-function mutation in the ATP-binding cassette subfamily C member 8 (ABCC8) gene. Endocr J 2018;65:1055–9. https://doi.org/10.1507/endocrj.ej18-0054.Search in Google Scholar

9. Vaxillaire, M, Dechaume, A, Busiah, K, Cave, H, Pereira, S, Scharfmann, R, et al.. New ABCC8 mutations in relapsing neonatal diabetes and clinical features. Diabetes 2007;56:1737–41. https://doi.org/10.2337/db06-1540.Search in Google Scholar PubMed

10. Patch, AM, Flanagan, SE, Boustred, C, Hattersley, AT, Ellard, S. Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period. Diabetes Obes Metab 2007;9:S28–39. https://doi.org/10.1111/j.1463-1326.2007.00772.x.Search in Google Scholar PubMed PubMed Central

11. Seino, S, Miki, T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol 2003;81:133–76. https://doi.org/10.1016/s0079-6107(02)00053-6.Search in Google Scholar PubMed

12. Nichols, CG. KATP channels as molecular sensors of cellular metabolism. Nature 2006;440:470–6. https://doi.org/10.1038/nature04711.Search in Google Scholar PubMed

Received: 2020-08-06

Accepted: 2020-09-26

Published Online: 2020-11-13

Published in Print: 2021-02-23

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/jpem-2020-0462

Keywords for this article

monogenic diabetes; sulfonylurea; case report