Gao AM, Deng WL, Yang XP, Wu WY, Ma CY, Liu Y. WFS1 gene mutation associated with pediatric diabetes mellitus and congenital deafness: A case report. World J Diabetes 2025; 16(8): 108946 [DOI: 10.4239/wjd.v16.i8.108946]
Corresponding Author of This Article
Yu Liu, Chief Physician, Department of Pediatric Endocrinology, Genetics and Metabolism, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, No. 63 Ruijin South Road, Nanming District, Guiyang 550000, Guizhou Province, China. yuliudoctor2@163.com
Research Domain of This Article
Pediatrics
Article-Type of This Article
Case Report
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ai-Min Gao, Wan-Ling Deng, Xin-Ping Yang, Wan-Yue Wu, Chun-Yuan Ma, Yu Liu, Department of Pediatric Endocrinology, Genetics and Metabolism, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, Guiyang 550000, Guizhou Province, China
Author contributions: Liu Y and Gao AM the principal investigators, conceived the study and revised the manuscript; Gao AM, Yang XP, Deng WL, Wu WY, and Ma CY collected the data and drew the figures and tables; Gao AM wrote the manuscript; Liu Y revised the manuscript; all authors critically reviewed the article and approved the final manuscript.
Supported by Beijing Holistic Integrative Medicine Association Clinical Research Funding Program, No. ZHKY-2024-2209.
Informed consent statement: Informed consent was obtained from the patient's parents for all procedures, genetic testing, and publication of the case details and images. The study protocol was reviewed and approved by the Institutional Review Board of Guiyang Maternal and Child Health Care Hospital (No. 2025-15), ensuring compliance with the Declaration of Helsinki and ethical standards for research involving human subjects.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu Liu, Chief Physician, Department of Pediatric Endocrinology, Genetics and Metabolism, Guiyang Maternal and Child Health Care Hospital, Guiyang Children's Hospital, No. 63 Ruijin South Road, Nanming District, Guiyang 550000, Guizhou Province, China. yuliudoctor2@163.com
Received: April 28, 2025 Revised: June 2, 2025 Accepted: July 14, 2025 Published online: August 15, 2025 Processing time: 109 Days and 3.2 Hours
Abstract
BACKGROUND
Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration, most notably sensorineural hearing loss and optic atrophy. Because its initial manifestations are usually similar to those of type 1 diabetes, the diagnosis may be delayed until other manifestations appear. Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis, but the complete mutation spectrum of WFS1 has not been fully determined. Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance, as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.
CASE SUMMARY
A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia, polyuria, and polyphagia, and was diagnosed with diabetic ketoacidosis and impaired insulin secretion. Sensorineural hearing loss was also detected. Whole-exome sequencing identified a previously unreported heterozygous mutation, WFS1 c.986T>C (p.Phe329Ser), in the patient and her father, confirming the diagnosis of Wolfram syndrome. Bioinformatic analysis supported the likely pathogenicity of this mutation. In silico pathogenicity predictors (REVEL, SIFT, PolyPhen-2, MutationTaster, and GERP+) supported a deleterious effect on wolframin structure and function. The patient was initially treated with intravenous insulin and fluid resuscitation, then transitioned to a basal–bolus insulin regimen. Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections. At the 1- and 6-month follow-ups, blood glucose remained well controlled (hemoglobin A1c: 5.89% and 6.58%, respectively), with no evidence of organ dysfunction or further complications.
CONCLUSION
This case identifies WFS1 c.986T>C (p.Phe329Ser) as a novel pathogenic variant causing Wolfram syndrome. It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis, individualized therapy, and comprehensive family support.
Core Tip: A 2yearold girl with diabetic ketoacidosis and congenital deafness was found to carry a novel heterozygous WFS1 mutation (c.986T>C, p.Phe329Ser). Rapid wholeexome sequencing confirmed Wolfram syndrome, guiding timely metabolic correction, insulin therapy, audiologic support, and genetic counseling. This previously unreported variant expands the WFS1 mutational spectrum and underscores the value of early genetic testing in children whose diabetes presents with atypical features such as sensorineural hearing loss.
