Copyright
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
Molecular profiles and long-term outcomes of Thai children with hepatic glycogen storage disease in Thailand
Jaravee Vanduangden, Rungnapa Ittiwut, Chupong Ittiwut, Teerasak Phewplung, Anapat Sanpavat, Palittiya Sintusek, Kanya Suphapeetiporn
Jaravee Vanduangden, Department of Pediatrics, Chulalongkorn University, Bangkok 10330, Thailand
Rungnapa Ittiwut, Center of Excellence for Medical Genomics, Department of Pediatrics, Excellence Center for Genomics and Precision Medicine, Chulalongkorn University, Bangkok 10330, Thailand
Chupong Ittiwut, Department of Pediatrics, Excellence Center of Genomics and Precision Medicine, Bangkok 10330, Thailand
Teerasak Phewplung, Department of Radiology, Chulalongkorn University, Bangkok 10330, Thailand
Anapat Sanpavat, Department of Pathology, Chulalongkorn University, Bangkok 10330, Thailand
Palittiya Sintusek, Center of Excellence in Thai Pediatric Gastroenterology, Hepatology and Immunology, Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
Kanya Suphapeetiporn, Center of Excellence for Medical Genetics, Department of Pediatrics, King Chulalongkorn Mem Hosp, Dept Pediat, Div Med Genet and Metab, Sor Kor Bldg, Chulalongkorn University, Bangkok 10330, Thailand
Co-corresponding authors: Palittiya Sintusek and Kanya Suphapeetiporn.
Author contributions: Suphapeetiporn K, Sintusek P and Vanduangden J designed the manuscript, wrote the manuscript; Suphapeetiporn K, Sintusek P collected the data and drafted the manuscript; Ittiwut R and Ittiwut C analyzed the sequencing data and wrote the manuscript; Phewplung T prepared and provided the liver tumor images; Sanpavat A interpreted and prepared the histopathology images. All authors have read and approved the final manuscript.
Supported by Ratchadaphiseksomphot Fund, Graduate Affairs, Faculty of Medicine, Chulalongkorn University, No. GA66/020; and Ratchadaphiseksomphot Fund, Chulalongkorn University, No. RCU_H_64_007_30.
Institutional review board statement: The protocol of the study was approved by the Institute Research Board at Chulalongkorn University, Bangkok, Thailand (IRB No. 0678/65).
Informed consent statement: Written informed assent and/or informed consent for this study were obtained from the patients and/or their parents.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: Correspondence and requests for materials should be addressed to Palittiya Sintusek.
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: Palittiya Sintusek, MD, MSc, PhD, Associate Professor, Center of Excellence in Thai Pediatric Gastroenterology, Hepatology and Immunology, Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 Rama IV, Pathumwan, Bangkok 10330, Thailand.
palittiya.s@chula.ac.th
Received: August 18, 2024
Revised: September 28, 2024
Accepted: October 16, 2024
Published online: December 9, 2024
Processing time: 73 Days and 4.2 Hours
BACKGROUND
Thus far, genetic analysis of patients clinically diagnosed with glycogen storage diseases (GSDs) in Thailand has not been reported.
AIM
To evaluate the clinical and biochemical profiles, molecular analysis and long-term outcomes of Thai children diagnosed with hepatic GSD.
METHODS
Children aged < 18 years diagnosed with hepatic GSD and followed up at King Chulalongkorn Memorial Hospital were recruited. Whole-exome sequencing (WES) was performed to identify the causative gene variants. Medical records were assessed.
RESULTS
All eight children with histopathologically confirmed diagnosis were classified by WES into subtypes Ia (n = 1), III (n = 3), VI (n = 3), and IX (n = 1). A total number of 10 variants were identified including G6PC (n = 1), AGL (n = 4), PYGL (n = 5), and PHKA2 (n = 1). AGL had two novel variants. The clinical manifestations were hepatomegaly (n = 8), doll-like facies (n = 3), wasting (n = 2), and stunting (n = 5). All patients showed hypoglycemia, transaminitis, and dyslipidemia. The mainstay of treatment was cornstarch supplementation and high-protein and low-lactose-fructose diet. After a median follow-up time of 9.59 years, height turned to normal for age in 3/5 patients and none had malnutrition. Liver enzymes, blood sugar, and lipid profiles improved in all.
CONCLUSION
Hepatomegaly, transaminitis, and hypoglycemia are the hallmarks of GSD confirmed by liver histopathology. Molecular analysis can confirm the diagnosis or classify the subtype that might benefit from personalized treatment, prognosis, and long-term care.
Core Tip: Hepatic glycogen storage diseases (GSDs) are rare but treatable conditions. While liver histopathology is helpful for diagnosis, it cannot differentiate between GSD subtypes. Data on long-term outcomes with extensive nutritional management are limited. This study evaluates the clinical and biochemical profiles, molecular analysis, and long-term outcomes of Thai children with hepatic GSDs, identifying two novel causative variants. The findings indicate that extensive nutritional management, including frequent uncooked cornstarch supplementation, a high-protein diet, and a low lactose-fructose diet, yields favorable outcomes across GSD subtypes. However, tailored management, particularly for GSD types III and VI, can further enhance quality of life and minimize complications.
