HIRSCHSPRUNG'S DISEASE- DIAGNOSIS, TREATMENT AND NEW THERAPEUTIC STRATEGIES
Abstract
Hirschsprung's disease (HD, HSCR) is a congenital disorder of intestinal motility characterized by aganglionosis. It is the absence of ganglion cells in the nerve plexuses of the large intestine. It leads to peristalsis disorders and functional obstruction. The disease most often manifests itself in the neonatal period as delayed meconium passage, abdominal distension, vomiting, and symptoms of obstruction. Confirmation of the diagnosis requires a rectal biopsy with histopathological evaluation. Treatment consists of surgical removal of the aganglionic segment of the intestine and restoration of the continuity of the gastrointestinal tract. The choice of surgical method depends mainly on the surgeon's preference and the experience of the center. A common complication is Hirschsprung-associated enterocolitis (HAEC), which may occur before or after surgery. Research is currently underway on the use of cell therapy in the treatment of HD. The review presents the epidemiology, pathogenesis, diagnosis, and current therapeutic strategies for Hirschsprung's disease, with particular emphasis on recent reports from the scientific literature. We highlight also new directions in research and therapeutic perspectives.
Aim of this study: The objective of this study is to summarise the latest information on Hirschsprung's disease, including research on cell therapies and treatments aimed at tissue regeneration.
Materials and methods: A literature review was conducted using the professional PubMed database. Articles published between 2018 and 2025 were included. The searches included combinations of the keywords: “Hirschsprung's disease,” “pediatric surgery,” “aganglionosis,” and “stem cell therapy”.
References
Diposarosa R, Bustam NA, Sahiratmadja E, Susanto PS, Sribudiani Y. Literature review: enteric nervous system development, genetic and epigenetic regulation in the etiology of Hirschsprung's disease. Heliyon. 2021 Jun 15;7(6):e07308. doi: 10.1016/j.heliyon.2021.e07308.
Montalva L, Cheng LS, Kapur R, Langer JC, Berrebi D, Kyrklund K, Pakarinen M, de Blaauw I, Bonnard A, Gosain A. Hirschsprung disease. Nat Rev Dis Primers. 2023 Oct 12;9(1):54. doi: 10.1038/s41572-023-00465-y.
Mueller JL, Hotta R. Current and future state of the management of Hirschsprung disease. World J Pediatr Surg. 2025 Mar 31;8(1):e000860. doi: 10.1136/wjps-2024-000860.
Yoshimaru K, Matsuura T, Uchida Y, Sonoda S, Maeda S, Kajihara K, Kawano Y, Shirai T, Toriigahara Y, Kalim AS, Zhang XY, Takahashi Y, Kawakubo N, Nagata K, Yamaza H, Yamaza T, Taguchi T, Tajiri T. Cutting-edge regenerative therapy for Hirschsprung disease and its allied disorders. Surg Today. 2024 Sep;54(9):977-994. doi: 10.1007/s00595-023-02741-6.
Lin H, You J, Hao L, Zheng Z, Zhou J, Xiao J, Feng J, Chen F. Tracing the enteric neural crest cell pathway from origin to colonization: insights into Hirschsprung's disease. Mol Biol Rep. 2025 Nov 11;53(1):64. doi: 10.1007/s11033-025-11211-w.
Sunardi M, Ito K, Sato Y, Uesaka T, Iwasaki M, Enomoto H. A Single RET Mutation in Hirschsprung Disease Induces Intestinal Aganglionosis Via a Dominant-Negative Mechanism. Cell Mol Gastroenterol Hepatol. 2023;15(6):1505-1524. doi: 10.1016/j.jcmgh.2022.12.003.
Fine RD, Chubaryov R, Fu M, Grullon G, Chakravarti A. Joint disruption of Ret and Ednrb transcription shifts cell fate trajectories in the enteric nervous system in Hirschsprung disease. Proc Natl Acad Sci U S A. 2025 Oct 28;122(43):e2507062122. doi: 10.1073/pnas.2507062122.
Chatterjee S, Chakravarti A. A gene regulatory network explains RET-EDNRB epistasis in Hirschsprung disease. Hum Mol Genet. 2019 Sep 15;28(18):3137-3147. doi: 10.1093/hmg/ddz149.
Bahreini F, Mahdavinezhad A, Eghbali M. Association of the RET Intronic Variant rs2435357 on Hirschsprung's Disease Susceptibility: A Systematic Review and Meta-Analysis. Iran J Public Health. 2025 Mar;54(3):567-577. doi: 10.18502/ijph.v54i3.18249.
Wang XX, Doisy W, Goro S, Harichane S, Rousseau M, Bellaiche M, Jung C. Epidemiology and Surgical Management of Hirschsprung's Disease in France: A 12-Year Retrospective Analysis (2012-2023). Acta Paediatr. 2025 Oct;114(10):2526-2534. doi: 10.1111/apa.70127.
Hagens J, Reinshagen K, Tomuschat C. Prevalence of Hirschsprung-associated enterocolitis in patients with Hirschsprung disease. Pediatr Surg Int. 2022 Jan;38(1):3-24. doi: 10.1007/s00383-021-05020-y.
Ziogas IA, Kuruvilla KP, Fu M, Gosain A. Hirschsprung-associated enterocolitis: a comprehensive review. World J Pediatr Surg. 2024 Oct 14;7(3):e000878. doi: 10.1136/wjps-2024-000878.
Chen Y, Yuan X, Li Y, Wu S, Miao X, Gong J, Huang Y. The prevalence and clinical presentation of Hirschsprung's disease in preterm infants: a systematic review and meta-analysis. Pediatr Surg Int. 2022 Apr;38(4):523-532. doi: 10.1007/s00383-021-05054-2.
Braun Y, Friedmacher F, Theilen TM, Fiegel HC, Weber K, Harter PN, Rolle U. Diagnosis of Hirschsprung disease by analyzing acetylcholinesterase staining using artificial intelligence. J Pediatr Gastroenterol Nutr. 2024 Sep;79(3):729-737. doi: 10.1002/jpn3.12339.
Pini Prato A, Erculiani M, Novi ML, Caraccia M, Grandi A, Casella S, Giacometti L, Montobbio G, Mottadelli G. Delayed diagnosis in Hirschsprung disease. Pediatr Surg Int. 2024 Mar 4;40(1):65. doi: 10.1007/s00383-024-05657-5.
Morera C, Nurko S. Hirschsprung's disease. Management. Aliment Pharmacol Ther. 2024 Jul;60 Suppl 1:S66-S76. doi: 10.1111/apt.18068.
Gołębiewski A, Anzelewicz S, Sosińska D, Osajca-Kanyion M. Transanal Endorectal Pull-Through for Hirschsprung's Disease: Complications and Lessons from Our Practice and the Literature. Children (Basel). 2024 Aug 29;11(9):1059. doi: 10.3390/children11091059.
Almadhoun MKIK, Morcos RKA, Alsadoun L, Bokhari SFH, Ahmed Z, Khilji F, Hasan AH, Bakht D, Abuelgasim O, Altayb Ismail MA. Minimally Invasive Surgery for Hirschsprung Disease: Current Practices and Future Directions. Cureus. 2024 Aug 8;16(8):e66444. doi: 10.7759/cureus.66444.
Langeron M, Alliot H, Sable S, Ali L, Lengliné H, Pardessus P, Bonnard A, Montalva L. Robotic surgery for Hirschsprung disease: a systematic review and meta-analysis. J Robot Surg. 2025 Sep 30;19(1):649. doi: 10.1007/s11701-025-02836-x.
Sun D, Zhang X, Xu Q, Li Y, Zhang Q, Wang D, Mu W, Hou P, Li A. Duhamel and transanal endorectal pull-throughs for Hirschsprung disease: a Bayesian network meta-analysis. BMC Surg. 2024 May 3;24(1):132. doi: 10.1186/s12893-024-02416-0.
Lindert J, Schulze F, Märzheuser S. Bowel Management in Hirschsprung Disease-Pre-, Peri- and Postoperative Care for Primary Pull-Through. Children (Basel). 2024 May 13;11(5):588. doi: 10.3390/children11050588.
Feng W, Zhang B, Fan L, Song A, Hou J, Die X, Liu W, Wang Y, Guo Z. Clinical characteristics and influence of postoperative Hirschsprung-associated enterocolitis: retrospective study at a tertiary children's hospital. Pediatr Surg Int. 2024 Apr 13;40(1):106. doi: 10.1007/s00383-024-05688-y.
Soh HJ, Nataraja RM, Pacilli M. Prevention and management of recurrent postoperative Hirschsprung's disease obstructive symptoms and enterocolitis: Systematic review and meta-analysis. J Pediatr Surg. 2018 Dec;53(12):2423-2429. doi: 10.1016/j.jpedsurg.2018.08.024.
Svetanoff WJ, Briggs K, Fraser JA, Lopez J, Fraser JD, Juang D, Aguayo P, Hendrickson RJ, Snyder CL, Oyetunji TA, St Peter SD, Rentea RM. Outpatient Botulinum Injections for Early Obstructive Symptoms in Patients with Hirschsprung Disease. J Surg Res. 2022 Jan;269:201-206. doi: 10.1016/j.jss.2021.07.017.
Jiang Z, Hou J, Die X, Liu W, Wang Y, Li H, Feng W, Wang Y. The association between short-term postoperative complications and bowel function after surgery for Hirschsprung disease. BMC Pediatr. 2025 Jul 2;25(1):514. doi: 10.1186/s12887-025-05861-9.
Short SS, Durham MM, Rollins MD. Hirschsprung disease outcomes. Semin Pediatr Surg. 2022 Apr;31(2):151160. doi: 10.1016/j.sempedsurg.2022.151160.
Zitouni H, Habachi G, Laamiri R, Jabloun A, Ben Ahmed Y, Thamri F, Kechiche N, Kerkeni Y, Ben Kraiem N, Bchini F, Barguelil M, Hellal Y, Sahnoun L, Jouini R, Jlidi S, Mhiri R. Assessment of Surgical Outcomes in Patients With Hirschsprung Disease: A 20-year Experience. J Pediatr Surg. 2025 Oct;60(10):162456. doi: 10.1016/j.jpedsurg.2025.162456.
Lewit RA, Kuruvilla KP, Fu M, Gosain A. Current understanding of Hirschsprung-associated enterocolitis: Pathogenesis, diagnosis and treatment. Semin Pediatr Surg. 2022 Apr;31(2):151162. doi: 10.1016/j.sempedsurg.2022.151162.
Hagens J, Reinshagen K, Tomuschat C. Prevalence of Hirschsprung-associated enterocolitis in patients with Hirschsprung disease. Pediatr Surg Int. 2022 Jan;38(1):3-24. doi: 10.1007/s00383-021-05020-y.
Zhang X, Sun D, Xu Q, Liu H, Li Y, Wang D, Wang J, Zhang Q, Hou P, Mu W, Jia C, Li A. Risk factors for Hirschsprung disease-associated enterocolitis: a systematic review and meta-analysis. Int J Surg. 2023 Aug 1;109(8):2509-2524. doi: 10.1097/JS9.0000000000000473.
Li S, Zhang Y, Li K, Liu Y, Chi S, Wang Y, Tang S. Update on the Pathogenesis of the Hirschsprung-Associated Enterocolitis. Int J Mol Sci. 2023 Feb 27;24(5):4602. doi: 10.3390/ijms24054602.
Encisco EM, Lim IIP, Velazco CS, Rosen NG, Garrison AP, Rymeski B, Frischer JS. Hirschsprung-Associated Enterocolitis at a Referral Institution: A Retrospective Review. J Pediatr Surg. 2023 Aug;58(8):1578-1581. doi: 10.1016/j.jpedsurg.2023.04.008.
Davidson JR, Kyrklund K, Eaton S, Pakarinen MP, Thompson DS, Cross K, Blackburn SC, De Coppi P, Curry J. Long-term surgical and patient-reported outcomes of Hirschsprung Disease. J Pediatr Surg. 2021 Sep;56(9):1502-1511. doi: 10.1016/j.jpedsurg.2021.01.043.
Dai Y, Deng Y, Lin Y, Ouyang R, Li L. Long-term outcomes and quality of life of patients with Hirschsprung disease: a systematic review and meta-analysis. BMC Gastroenterol. 2020 Mar 12;20(1):67. doi: 10.1186/s12876-020-01208-z.
Gunadi, Monica Carissa T, Stevie, Daulay EF, Yulianda D, Iskandar K, Dwihantoro A. Long-term functional outcomes of patients with Hirschsprung disease following pull-through. BMC Pediatr. 2022 May 3;22(1):246. doi: 10.1186/s12887-022-03301-6.
de Andres Crespo M, Byström C, Tyraskis A, Mutanen A, Stenström P, Hartman E, Danielsson J, Eaton S, De Coppi P, Löf Granström A, Wester T, Pakarinen M, Curry J, Loukogeorgakis S, Davidson J. Long-term effects of Hirschsprung disease in adults: meta-analysis and patient-level regression study. BJS Open. 2025 Oct 30;9(6):zraf107. doi: 10.1093/bjsopen/zraf107.
Pakarinen MP, Mutanen A. Long-term outcomes and quality of life in patients with Hirschsprung disease. World J Pediatr Surg. 2024 Oct 9;7(3):e000859. doi: 10.1136/wjps-2024-000859.
Zhang Y, Xiang X, Li X, Feng W, Guo Z. Early intervention in Hirschsprung's disease: effects on enterocolitis and surgical outcomes. BMC Pediatr. 2024 Jul 26;24(1):476. doi: 10.1186/s12887-024-04956-z.
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