Maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY): a 2-year follow-up study of six patients from a single diabetes center

Handan Jiang; Yue Luo; Xiufeng Huang; Huiping Wu; Xiaoou Shan

doi:10.1515/jpem-2025-0213

Article

Maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY): a 2-year follow-up study of six patients from a single diabetes center

Handan Jiang , Yue Luo , Xiufeng Huang , Huiping Wu and Xiaoou Shan

Published/Copyright: October 17, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 12

Abstract

Objectives

Summarize the clinical phenotypes and genotypic characteristics of Chinese pediatric patients with maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY).

Methods

Retrospective analysis of clinical characteristics, blood biochemical indexes, and genetic testing data was conducted on six children diagnosed with HNF1β-MODY followed in a single institution in Wenzhou from July 2020 to July 2024.

Results

Among the six children, three males and three females with a median age of diabetes onset at 12.3, four presented with pancreatic dysplasia. Extra-pancreatic manifestations included renal structural abnormalities(6/6), hypomagnesemia(6/6), hyperuricemia(4/6), elevated liver enzymes(4/6), hyperlipidemia(3/6), and genital tract malformation(1/6). Genetic testing identified a heterozygous HNF1β exon: 1–9 deletion in one patient, while the other five 17q12 microdeletions. Four children started insulin therapy at diagnosis, demonstrating no progressive decline in insulin secretion function and well-maintained insulin dependency. Six children received oral magnesium supplementation, and blood magnesium levels persisted at the lower limit of normal, without neuromuscular complications. Combined therapy with urinary alkalinizing agents and uricosuric drugs in three patients effectively maintained the serum urate levels, without observed progression. Hepatoprotective therapy decreased liver enzymes in two cases.

Conclusions

The clinical phenotype of HNF1β-MODY encompasses early-onset diabetes mellitus, pancreatic dysplasia, kidney disease, liver dysfunction, and genitourinary tract malformations, with refractory hypomagnesemia and hyperuricemia representing pathognomonic features. Early genetic confirmation can facilitate timely insulin initiation, guide targeted correction of electrolyte imbalances and metabolic disorders, and trigger proactive multi-organ monitoring for disease evolution.

Keywords: maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY); hepatocyte nuclear factor 1β (HNF1β); 17q12 microdeletion; follow-up study; genotype–phenotype correlation

Corresponding author: Yue Luo, Department of Pediatric Endocrinology, Heredity and Metabolism, The Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China, E-mail: luoyue1@wmu.edu.cn

Acknowledgments

We would like to thank all the patients as well as their parents for their consents to participate in the study.

Research ethics: The study protocol was in strict accordance with the tenets of the Declaration of Helsinki and has gained approval from the Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (LCKY2020-64) by March 20, 2022.
Informed consent: Informed consent was obtained from all individuals included in this study, or their legal guardians or wards.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. HJ conceptualized and designed the study. HJ and HW recruited patients and recorded clinical data. HJ and XH analyzed the data and wrote the manuscript. XS and YL gave constructive suggestions on the manuscript. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: The original data presented in the study are included in this article. Further inquiries can be directed to the corresponding author.

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Received: 2025-04-16

Accepted: 2025-09-04

Published Online: 2025-10-17

Published in Print: 2025-12-17

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Articles in the same Issue

https://doi.org/10.1515/jpem-2025-0213

Keywords for this article

maturity-onset diabetes of the young due to HNF1β variants (HNF1β-MODY); hepatocyte nuclear factor 1β (HNF1β); 17q12 microdeletion; follow-up study; genotype–phenotype correlation