Tian QJ, Zhang LJ, Zhang Q, Liu FC, Xie M, Cai JZ, Rao W. Protein-losing enteropathy and multiple vasculature dysplasia in LZTR1-related Noonan syndrome: A case report and review of literature. World J Gastroenterol 2025; 31(17): 105347 [DOI: 10.3748/wjg.v31.i17.105347]
Corresponding Author of This Article
Wei Rao, MD, PhD, Professor, Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao 266100, Shandong Province, China. qdfy_raowei@qdu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
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/
Qiu-Ju Tian, Qun Zhang, Feng-Chao Liu, Wei Rao, Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
Qiu-Ju Tian, Qun Zhang, Feng-Chao Liu, Jin-Zhen Cai, Wei Rao, Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
Lu-Jia Zhang, Department of Urology, Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao 266100, Shandong Province, China
Man Xie, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266100, Shandong Province, China
Co-first authors: Qiu-Ju Tian and Lu-Jia Zhang.
Author contributions: Tian QJ contributed to manuscript writing and editing, and data collection; Zhang LJ contributed to literature review, genetic analysis of Sanger sequencing and visualization of the protein structure; Tian QJ and Zhang LJ contributed equally as co-first authors; Zhang Q, Liu FC, and Xie M contributed to data collection and patient follow-up; Cai JZ contributed to the overall management of this patient; Rao W contributed to conceptualization and supervision; all authors have read and approved the final manuscript.
Supported by the Shandong Provincial Natural Science Foundation of China, No. ZR2023QH015; and Qingdao Municipal Natural Science Foundation of China, No. 23-2-1-134-zyyd-jch.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Wei Rao, MD, PhD, Professor, Division of Hepatology, Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao 266100, Shandong Province, China. qdfy_raowei@qdu.edu.cn
Received: January 27, 2025 Revised: March 31, 2025 Accepted: April 21, 2025 Published online: May 7, 2025 Processing time: 95 Days and 0.2 Hours
Abstract
BACKGROUND
Protein-losing enteropathy (PLE) is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia. Patients with Noonan syndrome may present with disorder of lymph vessel formation. However, PLE is rarely reported with Noonan syndrome.
CASE SUMMARY
A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia. Additional manifestations included a ventricular septal defect at birth, intermuscular hemangioma, slightly wide interocular and intermammary distances, and absence of the distal phalanx of the left little finger since birth. Abdominal computed tomography revealed cavernous transformation of the portal vein, and liver biopsy indicated “porto-sinusoidal vascular disease”. Whole exome and Sanger sequencing revealed a heterozygous mutation (exon9: C.850C>T:P.R284C) in leucine zipper-like transcription regulator 1, suggesting Noonan syndrome type 10. Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient. A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction. Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction, the patient achieved persistent normal serum albumin level without edema or diarrhea. Furthermore, the relevant literatures on Noonan syndrome and PLE were reviewed.
CONCLUSION
Herein, we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1 (c.850C>T:P.R284C) with newly reported manifestations. This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia, intestinal lymphangiectasia and PLE.
Core Tip: Protein-losing enteropathy (PLE) is rarely reported with Noonan syndrome. This case reported a rare mutation in leucine zipper-like transcription regulator 1 related to Noonan syndrome, thoracic duct abnormalities, small intestinal lymphangiectasia, PLE in a juvenile female with multiple vasculature dysplasia and congenital deformity of the little finger, and the successful treatment of hypoalbuminemia by microsurgical relief of the thoracic duct outlet obstruction. As far as we know, this is the first case describing PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1 (c.850C>T:P.R284C) with newly reported manifestations. Additionally, this report provides new evidence about the management of Noonan syndrome.
