Clinical characteristics and genetic analysis of maturity-onset diabetes of the young type 2 diagnosed in childhood

YE Juan; YE Feng; HOU Ling; WU Wei; LUO Xiao-Ping; LIANG Yan

doi:10.7499/j.issn.1008-8830.2408032

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Chinese Journal of Contemporary Pediatrics ›› 2025, Vol. 27 ›› Issue (1) : 94-100. DOI: 10.7499/j.issn.1008-8830.2408032

CLINICAL RESEARCH

Clinical characteristics and genetic analysis of maturity-onset diabetes of the young type 2 diagnosed in childhood

YE Juan, YE Feng, HOU Ling, WU Wei, LUO Xiao-Ping, LIANG Yan

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Abstract

Objective To study the clinical manifestations and genetic characteristics of children with maturity-onset diabetes of the young type 2 (MODY2), aiming to enhance the recognition of MODY2 in clinical practice. Methods A retrospective analysis was conducted on the clinical data of 13 children diagnosed with MODY2 at the Department of Pediatrics of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from August 2017 to July 2023. Results All 13 MODY2 children had a positive family history of diabetes and were found to have mild fasting hyperglycemia [(6.4±0.5) mmol/L] during health examinations or due to infectious diseases. In the oral glucose tolerance test, two cases met the diagnostic criteria for diabetes with fasting blood glucose, while the others exhibited impaired fasting glucose or impaired glucose tolerance. The one-hour post-glucose load (1-hPG) fluctuated between 8.31 and 13.06 mmol/L, meeting the diagnostic criteria for diabetes recommended by the International Diabetes Federation. All 13 MODY2 children had heterozygous variants in the glucokinase (GCK) gene, with Cases 6 (GCK c.1047C>A, p.Y349X), 11 (GCK c.1146_1147ins GCAGAGCGTGTCTACGCGCGCTGCGCACATGTGC, p.S383Alafs*87), and 13 (GCK c.784_785insC, p.D262Alafs*13) presenting variants that had not been previously reported. Conclusions This study enriches the spectrum of genetic variations associated with MODY2. Clinically, children with a family history of diabetes, incidental findings of mild fasting hyperglycemia, and negative diabetes-related antibodies should be considered for the possibility of MODY2.

Key words

Monogenic diabetes / Maturity-onset diabetes of the young type 2 / GCK gene / Genotype / Child

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YE Juan, YE Feng, HOU Ling, WU Wei, LUO Xiao-Ping, LIANG Yan. Clinical characteristics and genetic analysis of maturity-onset diabetes of the young type 2 diagnosed in childhood[J]. Chinese Journal of Contemporary Pediatrics. 2025, 27(1): 94-100 https://doi.org/10.7499/j.issn.1008-8830.2408032

References

1 Broome DT, Pantalone KM, Kashyap SR, et al. Approach to the patient with MODY-monogenic diabetes[J]. J Clin Endocrinol Metab, 2021, 106(1): 237-250. PMID: 33034350. PMCID: PMC7765647. DOI: 10.1210/clinem/dgaa710.
2 Tosur M, Philipson LH. Precision diabetes: lessons learned from maturity-onset diabetes of the young (MODY)[J]. J Diabetes Investig, 2022, 13(9): 1465-1471. PMID: 35638342. PMCID: PMC9434589. DOI: 10.1111/jdi.13860.
3 Hulín J, ?kopková M, Valkovi?ová T, et al. Clinical implications of the glucokinase impaired function: GCK MODY today[J]. Physiol Res, 2020, 69(6): 995-1011. PMID: 33129248. PMCID: PMC8549873. DOI: 10.33549/physiolres.934487.
4 Shields BM, Hicks S, Shepherd MH, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing?[J]. Diabetologia, 2010, 53(12): 2504-2508. PMID: 20499044. DOI: 10.1007/s00125-010-1799-4.
5 Sanyoura M, Philipson LH, Naylor R. Monogenic diabetes in children and adolescents: recognition and treatment options[J]. Curr Diab Rep, 2018, 18(8): 58. PMID: 29931562. PMCID: PMC6312113. DOI: 10.1007/s11892-018-1024-2.
6 American Diabetes Association. Standards of medical care in diabetes-2022 abridged for primary care providers[J]. Clin Diabetes, 2022, 40(1): 10-38. PMID: 35221470. PMCID: PMC8865785. DOI: 10.2337/cd22-as01.
7 Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim. 2015.30.
8 Liang H, Zhang Y, Li M, et al. Recognition of maturity-onset diabetes of the young in China[J]. J Diabetes Investig, 2021, 12(4): 501-509. PMID: 32741144. PMCID: PMC8015824. DOI: 10.1111/jdi.13378.
9 中华医学会内分泌学分会内分泌罕见病学组. 葡萄糖激酶基因突变导致的单基因糖尿病诊治专家共识[J]. 国际内分泌代谢杂志, 2022, 42(3): 236-244. DOI: 10.3760/cma.j.cn121383-20220107-01010.
10 Kawakita R, Hosokawa Y, Fujimaru R, et al. Molecular and clinical characterization of glucokinase maturity-onset diabetes of the young (GCK-MODY) in Japanese patients[J]. Diabet Med, 2014, 31(11): 1357-1362. PMID: 24804978. DOI: 10.1111/dme.12487.
11 Lopez AP, de Dios A, Chiesa I, et al. Analysis of mutations in the glucokinase gene in people clinically characterized as MODY2 without a family history of diabetes[J]. Diabetes Res Clin Pract, 2016, 118: 38-43. PMID: 27289208. DOI: 10.1016/j.diabres.2016.04.057.
12 Steele AM, Shields BM, Wensley KJ, et al. Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia[J]. JAMA, 2014, 311(3): 279-286. PMID: 24430320. DOI: 10.1001/jama.2013.283980.
13 Bergman M, Manco M, Satman I, et al. International diabetes federation position statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes[J]. Diabetes Res Clin Pract, 2024, 209: 111589. PMID: 38458916. DOI: 10.1016/j.diabres.2024.111589.
14 Younis H, Ha SE, Jorgensen BG, et al. Maturity-onset diabetes of the young: mutations, physiological consequences, and treatment options[J]. J Pers Med, 2022, 12(11): 1762. PMID: 36573710. PMCID: PMC9697644. DOI: 10.3390/jpm12111762.
15 Caetano LA, Jorge AA, Malaquias AC, et al. Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects[J]. Arq Bras Endocrinol Metabol, 2012, 56(8): 519-524. PMID: 23295292. DOI: 10.1590/s0004-27302012000800010.
16 Delvecchio M, Pastore C, Giordano P. Treatment options for MODY patients: a systematic review of literature[J]. Diabetes Ther, 2020, 11(8): 1667-1685. PMID: 32583173. PMCID: PMC7376807. DOI: 10.1007/s13300-020-00864-4.
17 Timsit J, Ciangura C, Dubois-Laforgue D, et al. Pregnancy in women with monogenic diabetes due to pathogenic variants of the glucokinase gene: lessons and challenges[J]. Front Endocrinol (Lausanne), 2022, 12: 802423. PMID: 35069449. PMCID: PMC8766338. DOI: 10.3389/fendo.2021.802423.
18 Aarthy R, Aston-Mourney K, Mikocka-Walus A, et al. Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY): a review[J]. J Diabetes Complications, 2021, 35(1): 107640. PMID: 32763092. DOI: 10.1016/j.jdiacomp.2020.107640.
19 Elias-Assad G, Saab R, Molnes J, et al. Maturity onset diabetes of the young type 2 (MODY2): insight from an extended family[J]. Diabetes Res Clin Pract, 2021, 175: 108791. PMID: 33812904. DOI: 10.1016/j.diabres.2021.108791.