Case Report
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Oct 6, 2023; 11(28): 6831-6840
Published online Oct 6, 2023. doi: 10.12998/wjcc.v11.i28.6831
Multi-organ hereditary hemorrhagic telangiectasia: A case report
Ying-Ling Chen, Hong-Yue Jiang, Dong-Ping Li, Jiang Lin, Yun Chen, Li-Li Xu, Hong Gao
Ying-Ling Chen, Hong-Yue Jiang, Dong-Ping Li, Yun Chen, Li-Li Xu, Hong Gao, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Jiang Lin, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Jiang Lin, Shanghai Institute of Medical Imaging, Shanghai 200032, China
Author contributions: Chen YL contributed to manuscript writing and experiment performance; Jiang HY performed the majority of the experiments; Li DP, Chen Y, and Xu LL contributed to revision of the manuscript; Lin J interpreted the computed tomography scan results; Gao H recruited the patient and contributed to the supervision of the entire study; and all authors read and approved the final manuscript.
Informed consent statement: Informed written consent was obtained from the patient for the publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016) and revised the manuscript according to the requirements of 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: Hong Gao, MD, Doctor, Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China. gao.hong@zs-hospital.sh.cn
Received: July 11, 2023
Peer-review started: July 11, 2023
First decision: August 4, 2023
Revised: August 21, 2023
Accepted: September 11, 2023
Article in press: September 11, 2023
Published online: October 6, 2023
Processing time: 75 Days and 12.6 Hours
Abstract
BACKGROUND

Type 2 hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease and is associated with ALK1 gene mutations. Type 2 HHT patients primarily suffer from recurrent bleeding. There is currently no promising treatment.

CASE SUMMARY

A 5-year-old Chinese patient (III23) was admitted to Zhongshan Hospital for recurrent melena occurring over 2 mo. She had been experiencing epistaxis for years and had been diagnosed with idiopathic pulmonary hypertension 4 mo before presentation. Abdominal computed tomography examination showed hepatic arteriovenous malformation. Gene testing revealed a c.1121G>A mutation on the ALK1 gene. According to the international diagnostic criteria, this patient was diagnosed with HHT. In addition, 8 more family members exhibited HHT symptoms to varying degrees. Gene testing in 5 family members (2 with HHT symptoms and 3 without HHT symptoms) revealed the ALK1 c.1121G>A mutation in the 2 family members with HHT symptoms. This missense mutation results in the substitution of arginine for glutamine at amino acid position 374 (R374Q) in the conserved functional kinase domain of ALK1. Biological studies revealed that this mutation decreased the kinase activity of ALK1 and impeded the phosphorylation of its substrate Smad1. Moreover, the R374Q mutant downregulated the protein level of collagen-1, a fibrogenic factor, indicating abnormal fiber generation during vascular formation.

CONCLUSION

The R374Q mutant of ALK1 and its subsequent influence on fiber generation highly indicated its pathogenic role in this family with type 2 HHT. Detection of this gene mutation will facilitate early diagnosis of suspected type 2 HHT patients, and mechanistic studies will provide insights for future therapy.

Keywords: Hereditary hemorrhagic telangiectasia; Pedigree; ALK1; Gene mutation; Case report

Core Tip: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disease characterized by varying degrees of bleeding symptoms. The diagnosis of HHT is difficult when relying on bleeding symptoms, while gene testing is robust and reliable for identifying HHT patients. Here, we report a patient with type 2 HHT who was undiagnosed for HHT for years due to varied symptoms involving multiple organs. We found an ALK1 gene mutation in the patient and her family members. We further verified the pathogenic role of this mutation in inducing vascular malformation by basic research studies.