Diagnosis and Treatment of Neonatal Diabetes: a United States Experience

Overview

Journal Pediatr Diabetes

Publisher Wiley

Specialties Endocrinology
Pediatrics

Date 2008 Jul 30

PMID 18662362

Citations 49

Authors

Julie Stoy

Siri Atma W Greeley

Veronica P Paz

Honggang Ye

Ashley N Pastore

Kinga B Skowron

Rebecca B Lipton

Fran R Cogen

Graeme I Bell

Louis H Philipson

Affiliations

Soon will be listed here.

Abstract

Background/objective: Mutations in KCNJ11, ABCC8, or INS are the cause of permanent neonatal diabetes mellitus in about 50% of patients diagnosed with diabetes before 6 months of age and in a small fraction of those diagnosed between 6 and 12 months. The aim of this study was to identify the genetic cause of diabetes in 77 consecutive patients referred to the University of Chicago with diabetes diagnosed before 1 yr of age.

Methods: We used Oragene DNA Self-Collection kit to obtain a saliva sample for DNA. We sequenced the protein-coding regions of KCNJ11, ABCC8, and INS using standard methods.

Results: We enrolled 32 patients diagnosed with diabetes before 6 months of age and 45 patients diagnosed between 6 and 12 months. We identified a mutation in KCNJ11 in 14 patients from 12 families and in INS in 7 patients from 4 families. Three of the patients with an INS mutation were diagnosed with diabetes between 6 and 12 months of age. Finally, we found that two patients had an abnormality of chromosome 6q24 associated with transient neonatal diabetes mellitus.

Conclusions: We were able to establish a genetic cause of diabetes in 63% of patients diagnosed with diabetes before 6 months of age and in 7% of patients diagnosed between 6 and 12 months. Genetic testing, which is critical for guiding appropriate management, should be considered in patients diagnosed with diabetes before 1 yr of age, especially if they are autoantibody negative, although the presence of autoantibodies does not rule out a monogenic cause.

Citing Articles

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.

Management of Neonatal Diabetes due to a Mutation with Automated Insulin Delivery System and Remote Patient Monitoring.

Lee M, Gloyn A, Maahs D, Prahalad P Case Rep Endocrinol. 2023; 2023:8825724.

PMID: 37664823 PMC: 10468271. DOI: 10.1155/2023/8825724.

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus.

Sacks D, Arnold M, Bakris G, Bruns D, Horvath A, Lernmark A Diabetes Care. 2023; 46(10):e151-e199.

PMID: 37471273 PMC: 10516260. DOI: 10.2337/dci23-0036.

Case report: Neonatal diabetes mellitus caused by mutation presenting with intracranial hemorrhage.

Wu B, Xu W Front Neurol. 2023; 14:1072078.

PMID: 36937531 PMC: 10022729. DOI: 10.3389/fneur.2023.1072078.

Neonatal diabetes with a rare LRBA mutation.

Yadav A, Kumar R, Rawat A, Venkatesan R BMJ Case Rep. 2022; 15(11).

PMID: 36423945 PMC: 9693640. DOI: 10.1136/bcr-2022-250243.

References

Vaxillaire M, Populaire C, Busiah K, Cave H, Gloyn A, Hattersley A . Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients. Diabetes. 2004; 53(10):2719-22. DOI: 10.2337/diabetes.53.10.2719. View

Vaxillaire M, Dechaume A, Busiah K, Cave H, Pereira S, Scharfmann R . New ABCC8 mutations in relapsing neonatal diabetes and clinical features. Diabetes. 2007; 56(6):1737-41. DOI: 10.2337/db06-1540. View

Girard C, Shimomura K, Proks P, Absalom N, Castano L, Perez de Nanclares G . Functional analysis of six Kir6.2 (KCNJ11) mutations causing neonatal diabetes. Pflugers Arch. 2006; 453(3):323-32. DOI: 10.1007/s00424-006-0112-3. View

Edghill E, Dix R, Flanagan S, Bingley P, Hattersley A, Ellard S . HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months. Diabetes. 2006; 55(6):1895-8. DOI: 10.2337/db06-0094. View

Slingerland A . Monogenic diabetes in children and young adults: Challenges for researcher, clinician and patient. Rev Endocr Metab Disord. 2006; 7(3):171-85. PMC: 1894829. DOI: 10.1007/s11154-006-9014-0. View

Zung A, Glaser B, Nimri R, Zadik Z . Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2. J Clin Endocrinol Metab. 2004; 89(11):5504-7. DOI: 10.1210/jc.2004-1241. View

Gardner R, Mackay D, Mungall A, Polychronakos C, Siebert R, Shield J . An imprinted locus associated with transient neonatal diabetes mellitus. Hum Mol Genet. 2000; 9(4):589-96. DOI: 10.1093/hmg/9.4.589. View

Battin M, Yong C, Phang M, Daaboul J . Transient neonatal diabetes mellitus and macroglossia. J Perinatol. 1996; 16(4):288-91. View

Hermann R, Soltesz G . Prevalence and HLA association of GAD65 antibodies in Hungarian schoolchildren. Hum Immunol. 2003; 64(1):152-5. DOI: 10.1016/s0198-8859(02)00686-9. View

10.

Gach A, Wyka K, Malecki M, Noczynska A, Skupien J, Nazim J . Islet-specific antibody seroconversion in patients with long duration of permanent neonatal diabetes caused by mutations in the KCNJ11 gene. Diabetes Care. 2007; 30(8):2080-2. DOI: 10.2337/dc06-2440. View

11.

Stoy J, Edghill E, Flanagan S, Ye H, Paz V, Pluzhnikov A . Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007; 104(38):15040-4. PMC: 1986609. DOI: 10.1073/pnas.0707291104. View

12.

Stoffers D, Zinkin N, Stanojevic V, Clarke W, Habener J . Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequence. Nat Genet. 1997; 15(1):106-10. DOI: 10.1038/ng0197-106. View

13.

Stanik J, Gasperikova D, Paskova M, Barak L, Javorkova J, Jancova E . Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. J Clin Endocrinol Metab. 2007; 92(4):1276-82. PMC: 7611849. DOI: 10.1210/jc.2006-2490. View

14.

Polak M, Dechaume A, Cave H, Nimri R, Crosnier H, Sulmont V . Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group. Diabetes. 2008; 57(4):1115-9. DOI: 10.2337/db07-1358. View

15.

Sagen J, Raeder H, Hathout E, Shehadeh N, Gudmundsson K, Baevre H . Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy. Diabetes. 2004; 53(10):2713-8. DOI: 10.2337/diabetes.53.10.2713. View

16.

Patch A, Flanagan S, Boustred C, Hattersley A, 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 Suppl 2:28-39. PMC: 7611803. DOI: 10.1111/j.1463-1326.2007.00772.x. View

17.

Gloyn A, Pearson E, Antcliff J, Proks P, Bruining G, Slingerland A . Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N Engl J Med. 2004; 350(18):1838-49. DOI: 10.1056/NEJMoa032922. View

18.

Flanagan S, Patch A, Mackay D, Edghill E, Gloyn A, Robinson D . Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. Diabetes. 2007; 56(7):1930-7. PMC: 7611811. DOI: 10.2337/db07-0043. View

19.

Gloyn A, Siddiqui J, Ellard S . Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat. 2006; 27(3):220-31. DOI: 10.1002/humu.20292. View

20.

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. 2007; 7(6):352-60. DOI: 10.1111/j.1399-5448.2006.00217.x. View