Xie LD, Kong XM, Shen JX, Wang TL, Ma J, Zhang YF, Chen XP. Novel compound heterozygous mutations in the hemojuvelin gene in a juvenile hemochromatosis patient: A case report. World J Clin Cases 2024; 12(19): 3961-3970 [PMID: 38994316 DOI: 10.12998/wjcc.v12.i19.3961]
Corresponding Author of This Article
Xiao-Ping Chen, MD, PhD, Associate Professor, Chief Physician, Department of Endocrinology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing 100029, China. chenxiaoping@zryhyy.com.cn
Research Domain of This Article
Genetics & Heredity
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/
Ling-Ding Xie, Xiao-Mu Kong, Xiao-Ping Chen, Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China
Jing-Xia Shen, Department of Tumor Radiotherapy and Chemotherapy, Qian’an People’s Hospital, Qian’an 064400, Hebei Province, China
Tai-Ling Wang, Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
Jing Ma, Department of Endocrinology, Aksu First People's Hospital, Aksu Region 843000, Xinjiang Uygur Autonomous Region, China
Yun-Fen Zhang, Department of Metabolic Diseases, Qian’an Traditional Chinese Medical Hospital, Qian’an 064400, Hebei Province, China
Author contributions: Chen XP, Xie LD, Kong XM, and Shen JX designed and performed the study, investigated the pedigree; Chen XP, Xie LD, Shen JX, Zhang YF, and Ma J took care of the patient and collected the clinical data; Kong XM contributed to the gene analysis; Chen XP, Xie LD, and Kong XM interpreted the genetic data of the pedigree, drafted the first version of the manuscript; Wang TL examined the pathological sections of the liver; Chen XP completed the final version of the manuscript; supervised and managed the data. All the authors have read and approved the final manuscript and approved the submission of this work.
Supported byNational High Level Hospital Clinical Research Funding, No. 2022-NHLHCRF-LX-02-0101.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or conflicts of interest with respect to this manuscript.
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: Xiao-Ping Chen, MD, PhD, Associate Professor, Chief Physician, Department of Endocrinology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing 100029, China. chenxiaoping@zryhyy.com.cn
Received: February 27, 2024 Revised: May 8, 2024 Accepted: May 20, 2024 Published online: July 6, 2024 Processing time: 122 Days and 22.2 Hours
Abstract
BACKGROUND
Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload observed worldwide that leads to damage in multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH.
CASE SUMMARY
A 34-year-old male Chinese patient presented with liver fibrosis, diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, and skin hyperpigmentation. Biochemical test revealed a markedly elevated serum ferritin level of 4329 μg/L and a transferrin saturation rate of 95.4%. Targeted exome sequencing and Sanger sequencing revealed that the proband had a novel mutation c.863G>A (p.R288Q) in the HJV gene which was transmitted from his father, and two known mutations, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*) in cis, which were inherited from his mother. The p.R288W mutation was previously reported to be pathogenic for hemochromatosis, which strongly supported the pathogenicity of p.R288Q reported for the first time in this case. After 72 wk of intensive phlebotomy therapy, the patient achieved a reduction in serum ferritin to 160.5 μg/L. The patient's clinical symptoms demonstrated a notable improvement.
CONCLUSION
This study highlights the importance of screening for hemochromatosis in patients with diabetes and hypogonadotropic hypogonadism. It also suggests that long-term active phlebotomy could efficiently improve the prognosis in severe JH.
Core Tip: Juvenile hemochromatosis (JH) is an early-onset, rare autosomal recessive disorder of iron overload that causes damage to multiple organs. Pathogenic mutations in the hemojuvelin (HJV) gene are the major cause of JH. We presented a 34-year-old male Chinese patient with a novel HJV mutation c.863G>A (p.R288Q) and two known mutations in cis, c.18G>C (p.Q6H) and c.962_963delGCinsAA (p.C321*). The proband presented with diabetes, hypogonadotropic hypogonadism, hypophysis hypothyroidism, hyperpigmentation, liver fibrosis, a markedly elevated serum ferritin level of 4329 μg/L and a transferrin saturation rate of 95.4%. His condition improved after 72 wk of intensive phlebotomy therapy.
