Al Atrash E, Zourob D, Alghfeli H, AbdelMassih A. Fontan-related protein-losing enteropathy: A comprehensive review of pathophysiology and current therapies. World J Clin Pediatr 2026; 15(4): 119970 [DOI: 10.5409/wjcp.119970]
Corresponding Author of This Article
Eman Al Atrash, MD, Division of Pediatric Gastroenterology, Department of Pediatrics, Mediclinic Airport Hospital, Airport Road, Abu Dhabi 971, United Arab Emirates. emanalatrash8@gmail.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
review-article
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/
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
Share the Article
Al Atrash E, Zourob D, Alghfeli H, AbdelMassih A. Fontan-related protein-losing enteropathy: A comprehensive review of pathophysiology and current therapies. World J Clin Pediatr 2026; 15(4): 119970 [DOI: 10.5409/wjcp.119970]
World J Clin Pediatr. Dec 9, 2026; 15(4): 119970 Published online Dec 9, 2026. doi: 10.5409/wjcp.119970
Fontan-related protein-losing enteropathy: A comprehensive review of pathophysiology and current therapies
Eman Al Atrash, Doaa Zourob, Huda Alghfeli, Antoine AbdelMassih
Eman Al Atrash, Division of Pediatric Gastroenterology, Department of Pediatrics, Mediclinic Airport Hospital, Abu Dhabi 971, United Arab Emirates
Doaa Zourob, Al Mushrif Children’s Specialty Center, AHS, Pure Health Group, Abu Dhabi 971, United Arab Emirates
Huda Alghfeli, Division of Pediatric Gastroenterology, Department of Pediatrics, Burjeel Medical City, Abu Dhabi 971, United Arab Emirates
Antoine AbdelMassih, Division of Pediatric Cardiology, Department of Pediatrics, SKMC, Pure Health Group, Abu Dhabi 971, United Arab Emirates
Author contributions: Al Atrash E and AbdelMassih A wrote the management and conclusion; Zourob D wrote the introduction and pathophysiology; Alghfeli H wrote the clinical presentation and diagnosis; all of the authors read and approved the final version of the manuscript to be published.
AI contribution statement: AI tools were used only for language editing and improving clarity, and all scientific content is entirely the authors’ own.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
Corresponding author: Eman Al Atrash, MD, Division of Pediatric Gastroenterology, Department of Pediatrics, Mediclinic Airport Hospital, Airport Road, Abu Dhabi 971, United Arab Emirates. emanalatrash8@gmail.com
Received: February 12, 2026 Revised: February 26, 2026 Accepted: May 7, 2026 Published online: December 9, 2026 Processing time: 222 Days and 6.1 Hours
Abstract
Protein-losing enteropathy (PLE) is a condition characterized by the abnormal loss of serum proteins into the intestinal lumen, and it is one of the most challenging complications in individuals with Fontan circulation. It affects approximately 5%-12% of Fontan patients and is associated with increased morbidity and mortality. As these patients age and milder or transient forms of PLE are more frequently recognized, its incidence is expected to rise. Although early detection and recent advances in treatment have improved quality of life, the risk of death remains significant. This review explores the pathogenesis of PLE in Fontan patients and discusses current management strategies. Treatment options are diverse and include medical therapies such as pulmonary vasodilators to reduce pulmonary vascular resistance, alpha-adrenergic agents to enhance lymphatic tone and promote lymphatic peristalsis and interventional procedures such as widening the fenestration to decongest the inferior vena cava. Additionally, lymphatic embolization guided by liver lymphangiography has emerged as a promising therapeutic approach in refractory cases. This strategy reflects a shift from palliation toward targeted, pathophysiology-driven interventions that aim to improve outcomes and potentially delay the need for transplantation.
Core Tip: Fontan-associated protein-losing enteropathy is a rare but life-threatening complication of Fontan circulation, driven by abnormal hemodynamics, lymphatic dysfunction, and intestinal barrier injury. This review synthesizes current understanding of protein-losing enteropathy pathophysiology and highlights contemporary management strategies, including nutritional optimization, targeted pharmacologic therapies, and emerging lymphatic interventions. Particular emphasis is placed on individualized, mechanism-based treatment and the evolving role of advanced imaging and interventional techniques. Improved recognition and multidisciplinary care have enhanced outcomes; however, refractory disease remains challenging, underscoring the need for novel therapeutic approaches.
