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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Toppari, Jorma


IMPACT FACTOR 2018: 1.239

CiteScore 2018: 1.22

SCImago Journal Rank (SJR) 2018: 0.507
Source Normalized Impact per Paper (SNIP) 2018: 0.562

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2191-0251
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Volume 32, Issue 7

Issues

Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes

Zhu Ming-Qiang / Dai Yang-Li / Huang Ke / Wu Wei / Fu Jun-Fen / Zou Chao-Chun / Dong Guan-Ping
  • Corresponding author
  • Children’s Hospital of Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou 310051, China, Phone: +86-13757119832, Fax: +86-571-87033296
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Published Online: 2019-06-19 | DOI: https://doi.org/10.1515/jpem-2018-0446

Abstract

Background

To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY).

Methods

A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing.

Results

There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4–15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55–4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling.

Conclusions

Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

Keywords: GCK; maturity onset diabetes of the young; screening criteria

References

  • 1.

    Ledermann HM. Maturity-onset diabetes of the young (MODY) at least ten times more common in Europe than previously assumed. Diabetologia 1995;38:1482.PubMedCrossrefGoogle Scholar

  • 2.

    Shields BM, Hicks S, Shepherd MH, Colclough K, Hattersley AT, et al. Maturity-onset diabetes of the young (MODY): how many cases are we missing. Diabetologia 2010;53:2504–8.Web of SciencePubMedCrossrefGoogle Scholar

  • 3.

    Kropff J, Selwood MP, McCarthy MI, Farmer AJ, Owen KR. Prevalence of monogenic diabetes in young adults: a community-based, cross-sectional study in Oxfordshire, UK. Diabetologia 2011;54:1261–3.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 4.

    Pihoker C, Gilliam LK, Ellard S, Dabelea D, Davis C, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endocrinol Metab 2013;98:4055–62.Web of SciencePubMedCrossrefGoogle Scholar

  • 5.

    Rubio-Cabezas O, Hattersley AT, Njølstad PR, Mlynarski W, Ellard S, et al. ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents. Pediatr Diabetes 2014;15(Suppl 20):47–64.PubMedGoogle Scholar

  • 6.

    Flannick J, Johansson S, Njølstad PR. Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes. Nat Rev Endocrinol 2016;12:394–406.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 7.

    Heuvel-Borsboom H, de Valk HW, Losekoot M, Westerink J. Maturity onset diabetes of the young: seek and you will find. Neth J Med 2016;74:193–200.PubMedGoogle Scholar

  • 8.

    Anık A, Çatlı G, Abacı A, Böber E. Maturity-onset diabetes of the young (MODY): an update. J Pediatr Endocrinol Metab 2015;28:251–63.Web of SciencePubMedGoogle Scholar

  • 9.

    Kleinberger JW, Pollin TI. Undiagnosed MODY: time for action. Curr Diab Rep 2015;15:110.CrossrefPubMedGoogle Scholar

  • 10.

    Zhang M, Zhou JJ, Cui W, Li Y, Yang P, et al. Molecular and phenotypic characteristics of maturity-onset diabetes of the young compared with early onset type 2 diabetes in China. J Diabetes 2015;7:858–63.Web of SciencePubMedCrossrefGoogle Scholar

  • 11.

    Ng MC, Cockburn BN, Lindner TH, Yeung VT, Chow CC, et al. Molecular genetics of diabetes mellitus in Chinese subjects: identification of mutations in glucokinase and hepatocyte nuclear factor-1alpha genes in patients with early-onset type 2 diabetes mellitus/MODY. Diabet Med 1999;16:956–63.CrossrefPubMedGoogle Scholar

  • 12.

    Xu JY, Dan QH, Chan V, Wat NM, Tam S, et al. Genetic and clinical characteristics of maturity-onset diabetes of the young in Chinese patients. Eur J Hum Genet 2005;13:422–7.CrossrefPubMedGoogle Scholar

  • 13.

    Yorifuji T, Higuchi S, Kawakita R, Hosokawa Y, Aoyama T, et al. Genetic basis of early-onset, maturity-onset diabetes of the young-like diabetes in Japan and features of patients without mutations in the major MODY genes: dominance of maternal inheritance. Pediatr Diabetes 2018;19:1164–72.CrossrefWeb of SciencePubMedGoogle Scholar

  • 14.

    Ping XY, Hua XX, Lan FY, Jiang L, Chen C, et al. GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature. J Pediatr Endocrinol Metab 2016;29:959–64.PubMedWeb of ScienceGoogle Scholar

  • 15.

    Li X, Ting TH, Sheng H, Liang CL, Shao Y, et al. Genetic and clinical characteristics of Chinese children with glucokinase-maturity-onset diabetes of the young (GCK-MODY). BMC Pediatr 2018;18:101.Web of ScienceCrossrefGoogle Scholar

  • 16.

    Ellard S, Bellanné-Chantelot C, Hattersley AT. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young. Diabetologia 2008;51:546–53.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 17.

    Brunerova L, Rahelić D, Ceriello A, Broz J. Use of oral antidiabetic drugs in the treatment of maturity-onset diabetes of the young: a mini review. Diabetes Metab Res Rev 2018;34:e2940.CrossrefWeb of ScienceGoogle Scholar

  • 18.

    Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of diabetes in the young. Clin Diabetes Endocrinol 2016;2:18.CrossrefGoogle Scholar

  • 19.

    Hattersley AT, Patel KA. Precision diabetes: learning from monogenic diabetes. Diabetologia 2017;60:769–77.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 20.

    Stanik J, Dusatkova P, Cinek O, Valentinova L, Huckova M, et al. De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed. Diabetologia 2014;57:480–4.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 21.

    Ağladıoğlu SY, Aycan Z, Çetinkaya S, Baş VN, Önder A, et al. Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing. J Pediatr Endocrinol Metab 2016;29:487–96.Web of SciencePubMedGoogle Scholar

  • 22.

    Globa E, Zelinska N, Elblova L, Dusatkova P, Cinek O, et al. MODY in Ukraine: genes, clinical phenotypes and treatment. J Pediatr Endocrinol Metab 2017;30:1095–103.PubMedWeb of ScienceGoogle Scholar

  • 23.

    Johansson BB, Irgens HU, Molnes J, Sztromwasser P, Aukrust I, et al. Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry. Diabetologia 2017;60:625–35.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 24.

    Mohan V, Radha V, Nguyen TT, Stawiski EW, Pahuja KB, et al. Comprehensive genomic analysis identifies pathogenic variants in maturity-onset diabetes of the young (MODY) patients in South India. BMC Med Genet 2018;19:22.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 25.

    Anık A, Çatlı G, Abacı A, Sarı E, Yeşilkaya E, et al. Molecular diagnosis of maturity-onset diabetes of the young (MODY) in Turkish children by using targeted next-generation sequencing. J Pediatr Endocrinol Metab 2015;28:1265–71.Web of SciencePubMedGoogle Scholar

  • 26.

    Chapla A, Mruthyunjaya MD, Asha HS, Varghese D, Varshney M, et al. Maturity onset diabetes of the young in India – a distinctive mutation pattern identified through targeted next-generation sequencing. Clin Endocrinol (Oxf) 2015;82:533–42.PubMedCrossrefGoogle Scholar

About the article

Received: 2018-10-16

Accepted: 2019-05-04

Published Online: 2019-06-19

Published in Print: 2019-07-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Conflict of interest: There are no competing interests.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 32, Issue 7, Pages 759–765, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2018-0446.

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