Congenital Diabetes: Comprehensive Genetic Testing Allows for Improved Diagnosis and Treatment of Diabetes and Other Associated Features

Overview

Journal Curr Diab Rep

Publisher Current Science

Specialty Endocrinology

Date 2018 Jun 14

PMID 29896650

Citations 6

Authors

Lisa R Letourneau

Siri Atma W Greeley

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: The goal of this review is to provide updates on congenital (neonatal) diabetes from 2011 to present, with an emphasis on publications from 2015 to present.

Recent Findings: There has been continued worldwide progress in uncovering the genetic causes of diabetes presenting within the first year of life, including the recognition of nine new causes since 2011. Management has continued to be refined based on underlying molecular cause, and longer-term experience has provided better understanding of the effectiveness, safety, and sustainability of treatment. Associated conditions have been further clarified, such as neurodevelopmental delays and pancreatic insufficiency, including a better appreciation for how these "secondary" conditions impact quality of life for patients and their families. While continued research is essential to understand all forms of congenital diabetes, these cases remain a compelling example of personalized genetic medicine.

Citing Articles

Protective Effect of Black Rice Cyanidin-3-Glucoside on Testicular Damage in STZ-Induced Type 1 Diabetic Rats.

Zheng H, Hu Y, Zhou J, Zhou B, Qi S Foods. 2024; 13(5).

PMID: 38472840 PMC: 10931135. DOI: 10.3390/foods13050727.

The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022.

Rapini N, Delvecchio M, Mucciolo M, Ruta R, Rabbone I, Cherubini V J Clin Endocrinol Metab. 2024; 109(9):2349-2357.

PMID: 38408297 PMC: 11319002. DOI: 10.1210/clinem/dgae095.

Research on the changes and predictions of the burden of type 2 diabetes mellitus in Pacific Island countries from 1990 to 2019.

Li Y, Zhang H, Jiang Y PLoS One. 2023; 18(12):e0293681.

PMID: 38127863 PMC: 10735006. DOI: 10.1371/journal.pone.0293681.

Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry.

Bowden T, Letourneau-Freiberg L, Kandasamy B, Sanyoura M, Tian P, Harris A Front Clin Diabetes Healthc. 2022; 2.

PMID: 36330312 PMC: 9629510. DOI: 10.3389/fcdhc.2021.735548.

Growth and development in monogenic forms of neonatal diabetes.

Hammoud B, Greeley S Curr Opin Endocrinol Diabetes Obes. 2021; 29(1):65-77.

PMID: 34864759 PMC: 11056188. DOI: 10.1097/MED.0000000000000699.

References

De Franco E, Shaw-Smith C, Flanagan S, Shepherd M, Hattersley A, Ellard S . GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency. Diabetes. 2012; 62(3):993-7. PMC: 3581234. DOI: 10.2337/db12-0885. View

Senee V, Chelala C, Duchatelet S, Feng D, Blanc H, Cossec J . Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat Genet. 2006; 38(6):682-7. DOI: 10.1038/ng1802. View

Nishi M, Sasahara M, Shono T, Saika S, Yamamoto Y, Ohkawa K . A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset diabetes mellitus and aniridia. Diabet Med. 2005; 22(5):641-4. DOI: 10.1111/j.1464-5491.2005.01469.x. View

Greeley S, Naylor R, Cook L, Tucker S, Lipton R, Philipson L . Creation of the Web-based University of Chicago Monogenic Diabetes Registry: using technology to facilitate longitudinal study of rare subtypes of diabetes. J Diabetes Sci Technol. 2011; 5(4):879-86. PMC: 3192593. DOI: 10.1177/193229681100500409. View

Inoue H, Tanizawa Y, Wasson J, BEHN P, Kalidas K, Bernal-Mizrachi E . A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet. 1998; 20(2):143-8. DOI: 10.1038/2441. View

Sun C, Pei Z, Zhang M, Sun B, Yang L, Zhao Z . Recovered insulin production after thiamine administration in permanent neonatal diabetes mellitus with a novel solute carrier family 19 member 2 (SLC19A2) mutation. J Diabetes. 2017; 10(1):50-58. DOI: 10.1111/1753-0407.12556. View

De Franco E, Flanagan S, Yagi T, Abreu D, Mahadevan J, Johnson M . Dominant ER Stress-Inducing Mutations Underlie a Genetic Syndrome of Neonatal/Infancy-Onset Diabetes, Congenital Sensorineural Deafness, and Congenital Cataracts. Diabetes. 2017; 66(7):2044-2053. PMC: 5482085. DOI: 10.2337/db16-1296. View

Letourneau L, Carmody D, Wroblewski K, Denson A, Sanyoura M, Naylor R . Diabetes Presentation in Infancy: High Risk of Diabetic Ketoacidosis. Diabetes Care. 2017; 40(10):e147-e148. PMC: 5606305. DOI: 10.2337/dc17-1145. View

De Franco E, Flanagan S, Houghton J, Lango Allen H, Mackay D, Temple I . The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet. 2015; 386(9997):957-63. PMC: 4772451. DOI: 10.1016/S0140-6736(15)60098-8. View

10.

Lanning M, Carmody D, Szczerbinski L, Letourneau L, Naylor R, Greeley S . Hypoglycemia in sulfonylurea-treated KCNJ11-neonatal diabetes: Mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures. Pediatr Diabetes. 2017; 19(3):393-397. PMC: 5918230. DOI: 10.1111/pedi.12599. View

11.

Rabbone I, Barbetti F, Gentilella R, Mossetto G, Bonfanti R, Maffeis C . Insulin therapy in neonatal diabetes mellitus: a review of the literature. Diabetes Res Clin Pract. 2017; 129:126-135. DOI: 10.1016/j.diabres.2017.04.007. View

12.

Hwang J, Park S, Ye H, Sanyoura M, Pastore A, Carmody D . FOXP3 mutations causing early-onset insulin-requiring diabetes but without other features of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome. Pediatr Diabetes. 2017; 19(3):388-392. PMC: 5918222. DOI: 10.1111/pedi.12612. View

13.

Bowman P, Sulen A, Barbetti F, Beltrand J, Svalastoga P, Codner E . Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018; 6(8):637-646. PMC: 6058077. DOI: 10.1016/S2213-8587(18)30106-2. View

14.

Park S, Ye H, Steiner D, Bell G . Mutant proinsulin proteins associated with neonatal diabetes are retained in the endoplasmic reticulum and not efficiently secreted. Biochem Biophys Res Commun. 2009; 391(3):1449-54. PMC: 2817945. DOI: 10.1016/j.bbrc.2009.12.090. View

15.

Cryns K, Sivakumaran T, van den Ouweland J, Pennings R, Cremers C, Flothmann K . Mutational spectrum of the WFS1 gene in Wolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease. Hum Mutat. 2003; 22(4):275-87. DOI: 10.1002/humu.10258. View

16.

Carmody D, Pastore A, Landmeier K, Letourneau L, Martin R, Hwang J . Patients with KCNJ11-related diabetes frequently have neuropsychological impairments compared with sibling controls. Diabet Med. 2016; 33(10):1380-6. PMC: 5654490. DOI: 10.1111/dme.13159. View

17.

Taha D, Al-Harbi N, Al-Sabban E . Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome. J Pediatr Endocrinol Metab. 2008; 21(6):581-6. View

18.

Kapellen T, Heidtmann B, Lilienthal E, Rami-Merhar B, Engler-Schmidt C, Holl R . Continuous Subcutaneous Insulin Infusion in Neonates and Infants Below 1 Year: Analysis of Initial Bolus and Basal Rate Based on the Experiences from the German Working Group for Pediatric Pump Treatment. Diabetes Technol Ther. 2015; 17(12):872-9. DOI: 10.1089/dia.2015.0030. View

19.

Bonnefond A, Sand O, Guerin B, Durand E, De Graeve F, Huyvaert M . GATA6 inactivating mutations are associated with heart defects and, inconsistently, with pancreatic agenesis and diabetes. Diabetologia. 2012; 55(10):2845-2847. DOI: 10.1007/s00125-012-2645-7. View

20.

Greeley S, Naylor R, Philipson L, Bell G . Neonatal diabetes: an expanding list of genes allows for improved diagnosis and treatment. Curr Diab Rep. 2011; 11(6):519-32. PMC: 3226065. DOI: 10.1007/s11892-011-0234-7. View