Abstract
Total intestinal aganglionosis (TIA) is the most extreme and rare form of Hirschsprung disease (HD). Until few years ago TIA was considered to be a uniformly fatal condition. Survival has improved in the recent years with the advent of parenteral nutrition, innovative surgical techniques and small bowel transplantation. The purpose of this meta-analysis was to determine the clinical outcome of TIA following various surgical procedures. A meta-analysis of cases of TIA reported in the literature between 1985 and 2009 was performed. Detailed information was recorded regarding the extent of aganglionosis, surgical procedures performed and clinical outcome. In case of survivors, authors of reports were contacted to obtain the up-to-date clinical status of the patient. There were 68 cases of TIA reported worldwide, 40 (58.8%) males and 28 (41.2%) females. 6 (8.8%) patients had extension of aganglionosis up to the stomach, 19 (27.9%) up to the duodenum and 43 (63.2%) patients had aganglionosis up to 20 cm below the duodeno-jejunal flexure. Family history of HD was documented in 10 (14.7%) patients. RET-gene mutation were identified in 10 (71.4%) of the 14 patients investigated of RET germline mutations. Eleven patients (16.2%) died prior to surgical treatment, 25 patients (36.8%) only had jejunostomy, while 20 (29.4%) had Ziegler’s myectomy–myotomy. 12 (17.6%) patients received intestinal transplantation (ITx) or combined liver–intestinal transplantation (LITx). Forty-five (66.2%) patients died at ages ranging from 1 day to 8 years. Twenty-three (33.8%) patients were alive; the longest survivor was 10 years old after LITx. Innovative surgical procedures and parenteral nutrition have improved clinical outcome of patients with TIA in recent years. Intestinal transplantation appears promising in the management of TIA.
Similar content being viewed by others
References
Caniano DA, Ormsbee HS, Polito W et al (1985) Total intestinal aganglionosis. J Pediatr Surg 20:456–460
MacKinnon AE, Cohen S (1977) Total intestinal aganglionosis, an autosomal recessive condition? Arch Dis Child 52:898–899
Talwalker VC (1976) Aganglionosis of the entire bowel. J Pediatr Surg 11:213–216
Coran AG, Teitelbaum DH (2000) Recent advantages in the management of Hirschsprung’s disease. Am J of Surg 180:382–387
Solari V, Ennis S, Yoneda A et al (2003) Mutation analysis of the RET gene in total intestinal aganglionosis by wave DNA fragment analysis system. J Pediatr Surg 38:497–501
Rudin C, Jenny PM, Ohnacker H et al (1986) Absence of the enteric nervous system in the newborn: presentation of three patients and review of the literature. J Pediatr Surg 21:313–318
Rudin C, Jenny PM, Fliegel CP et al (1986) Zuelzer–Wilson’s syndrome and absence of the enteric nervous system. J Pediatr Surg 41:287–292
Stringel G (1986) Extensive intestinal aganglionosis including the ileum: a new surgical technique. J Pediatr Surg 21:667–670
Lantieri F, Griseri P, Amiel J (2008) The molecular genetics of Hirschsprung’s disease. In: Holschneider M, Puri P (eds) Hirschsprung’s disease and allied disorders. Springer, Heidelberg, pp 63–64
Fouquet V, De Lagausie P, Faure C et al (2002) Do prognostic factors exist for total colonic aganglionosis with ileal involvement? J Pediatr Surg 37:71–75
Kleinhaus S, Boley SJ, Sheran M et al (1979) Hirschsprung’s disease: a survey of the members of the surgical section of the American Academy of Pediatrics. J Pediatr Surg 14:588–597
Ikeda K, Goto S (1984) Diagnosis and treatment of Hirschsprung’s disease in Japan. Ann Surg 199:400–405
Tatekawa Y, Muraji T, Takamizawa S (2007) A case report of a patient with near total intestinal aganglionosis followed by the role of extended myectomy and synbiotics therapy. J Pediatr Surg 42:E9–E12
Goulet O, Ruemmele F (2006) Causes and management of intestinal failure in children. Gastroenterology 130:S16–S28
Fortuna RS, Weber TR, Tracy TF et al (1996) Critical analysis of the operative treatment of Hirschsprung’s disease. Arch Surg 131:520–524
Marty TL, Seo T, Matlak ME et al (1995) Gastrointestinal function after surgical correction of Hirschsprung’s disease: long-term follow-up in 135 patients. J Pediatr Surg 30:655–658
Ziegler MM, Royal RE, Brandt J et al (1993) Extended myectomy–myotomy. A therapeutic alternative for total intestinal aganglionosis. Ann Surg 218:504–509
Saxton ML, Ein SH, Hoehner J, Kim PC (2000) Near-total intestinal aganglionosis: Long-term follow-up of a morbid condition. J Pediatr Surg 35:669–672
Shimotake T, Go S, Tomiyama H et al (2002) Proximal jejunostomy with or without myectomy–myotomy modification in five infants with total intestinal aganglionosis: an experience with surgical treatments in a single institution. J Pediatr Surg 37:835–839
Ziegler MM, Roos AJ, Bishop HC (1987) Total intestinal aganglionosis: a new technique for prolonged survival. J Pediatr Surg 22:82–83
Sauvat F, Grimaldi C, Lacaille F et al (2008) Intestinal transplantation for total intestinal aganglionosis: a series of 12 consecutive children. J Pediatr Surg 43:1833–1838
Sigurdsson L, Reyes J, Kocoshis SA et al (1999) Intestinal transplantation in children with chronic intestinal pseudo-obstruction. Gut 45:570–574
Rovera GM, Schoen RE, Goldbach B et al (2003) Intestinal and multivisceral transplantation: dynamics of nutritional management and functional autonomy. JPEN J Parenter Enter Nutr 27:1–8
Bond GF, Reyes JD (2004) Intestinal transplantation for total/near-total aganglionosis and intestinal pseudo obstruction. Semin Pediatr Surg 13:286–292
Bodian M, Carter CO, Ward BCH (1951) Hirschsprung’s disease. Lancet 1:302
Pasini B, Borrello MG, Greco A et al (1995) Loss of function effect of RET mutation causing Hirschsprung’s disease. Nat Genet 10:35–40
Dasgupta R, Langer JC (2004) Hirschsprung’s disease. Curr Probl Surg 41:942–988
Senyuez OF, Bueyuekuenal C, Oezbay G et al (1986) Jirasek-Zuelzer–Wilson syndrome. 2nd National Proctology Congress, Datca, Turkey, 15–18 September 1986
Puri P (2000) Hirschsprung’s disease: clinical generalities. In: Holzschneider AM, Puri P (eds) Hirschsprung’s disease and allied disorders. Harwood, Amsterdam, pp 129–135
Jasonni V, Martuciello G (1998) Total colonic aganglionosis. Semin Pediatr Surg 7(3):174–180
Herman RE, Izant RJ, Bolande RP (1963) Aganglionosis of the intestine in siblings. Surgery 53:664–669
Badner JA, Sieber WK, Garver KL et al (1990) A genetic study of Hirschsprung’s disease. Am J Hum Genet 46:568–580
Puri P (2003) Hirschsprung’s disease. In: Puri P (ed) Newborn surgery. Arnold, London, pp 513–534
Nemeth L, Yoneda A, Kader M et al (2001) Three-dimensional morphology of gut innervations in total intestinal aganglionosis using whole-mount preparation. J Pediatr Surg 36:291–295
Schiller M, Levy P, Shawa RA et al (1990) Familial Hirschsprung’s disease—a report of 22 affected siblings in four families. J Pediatr Surg 25:322–325
Engum SA, Petries M, Rescorla FJ et al (1993) Familial Hirschsprung’s disease: 20 cases in 12 kindreds. J Pediatr Surg 28(10):1286–1290
Boggs JD, Kidd JM (1958) Congenital abnormalities of intestinal innervations: absence of innervations in jejunum, ileum, colon in siblings. Pediatrics 21:261–265
Schuchardt A, D’Agati V, Larsson–Blomberg L et al (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 367:380–383
Luo Y, Cecchernin I, Pasini B et al (1993) Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung’s disease. Hum Mol Genet 21:1803–1808
Romeo G, Ronchetto P, Luo Y et al (1994) Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung’s disease. Nature 367:377–378
Edery P, Lyonnet S, Mulligan LM et al (1994) Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994;381–385
Kusafuka T, Puri P (1997) Altered RET gene mRNA expression in Hirschsprung’s disease. J Pediatr Surg 32:600–604
Kusafuka T, Puri P (1997) The RET proto-oncogene: a challenge to understanding of disease pathogenesis. Pediatr Surg Int 12:11–18
Martucciello G, Checcherini I, Lerone M et al (2000) Pathogenesis of Hirschsprung’s disease. J Pediatr Surg 35:1017–1025
Amiel J, Lyonnet S (2001) Hirschsprung’s disease, associated syndromes, and genetics: a review. J Med Genet 38:729–739
Ryan ET, Ecker JL, Christakis NA et al (1992) Hirschsprung’s disease: associated abnormalities and demography. J Pediatr Surg 27:76–81
Menezes M, Puri P (2005) Long-term clinical outcome in patients with Hirschsprung’s disease and associated Down’s syndrome. J Pediatr Surg 40:810–812
Brown R, Cywes S (2000) Disorders and congenital malformations associated with Hirschsprung’s disease. In: Holzschneider AM, Puri P (eds) Hirschsprung’s disease and allied disorders. Harwood, Amsterdam, pp 137–145
Chakravarti A, Lyonnet S (2001) Hirschsprung’s disease. In: Scriver CR, Beaudet AL, Sly WS et al (eds) The metabolic and molecular basis of inherited disease. McGraw Hill, New York, pp 6231–6255
Gariepy CE (2003) Genetic basis of Hirschsprung’s disease: implications in clinical practice. Mol Genet Metab 80:66–73
Waardenburg PJ (1951) A new syndrome combining developmental anomalies of the eyelids, eyebrows, and nose root with pigmentary defects of the iris and head hair and with congenital deafness. Am J Hum Genet 3:195
Shah KN, Dalal SJ, Desai MP et al (1981) White forelock, pigmentary disorder of irides, and long term segment Hirschsprung’s disease: possible variant of Waardenburg syndrome. J Pediatr 99:432–435
Toki F, Suzuki N, Inoue K et al (2003) Intestinal aganglionosis associated with the Waardenburg syndrome: report of two cases and review of the literature. Pediatr Surg Int 19:725–728
El-Halaby E, Coran AG (1994) Hirschsprung’s disease associated with Ondine’s curse: report of three cases and review of the literature. J Pediatr Surg 29:530–535
Nakahara S, Yokomori K, Tamura K et al (1995) Hirschsprung’s disease associated with Ondine’s curse: a special subgroup? J Pediatr Surg 30:1481–1484
Matsumoto K, Arima T, Izaki T et al (2002) Ondine’s curse associated with Hirschsprung’s disease and ganglioneuroblastoma. J Pediatr Gastroenterol Nutr 34:83–86
Sakai T, Wakizaka A, Matsuda H et al (1998) Point mutation in exon 12 of the receptor tyrosine kinase proto-oncogene RET in Ondine–Hirschsprung syndrome. Pediatrics 101:924–926
Fodstad H, Ljunggren B, Shawis R (1990) Ondine’s curse with Hirschsprung’s disease. Br J Neurosurg 4:87–93
Gross A, Kunze J, Maier RF et al (1995) Autosomal-recessive neural crest syndrome with albinism, black lock, cell migration disorder of the neurocytes of the gut, and deafness: ABCD syndrome. Am J Med Genet 56:322–326
Di Lorenzo M, Yazbeck S, Brochu P (1985) Aganglionosis of the entire bowel: four new cases and review of the literature. Br J Surg 72:657–658
Baynash AG, Hosoda K, Giaid A et al (1994) Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Cell 30:1277–1285
Edery P, Lyonnet S, Mulligan LM et al (1994) Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 367:378–380
Attie T, Pelet A, Edery P et al (1995) Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung’s disease. Hum Mol Genet 4:1381–1386
Ishor K, Kaufman S, Sudan D et al (2001) Long-term results of intestinal transplantation for pseudo-obstruction in children. J Pediatr Surg 36:174–177
Mittal N, Loinez C, Kato T et al (2003) Multivisceral transplantation for pediatric intestinal pseudo-obstruction: single center’s experience of 16 cases. The VIII international small bowel symposia, 2003
Sharif K, Beath SV, Kelly DA et al (2003) New perspective for the management of near-total or total intestinal aganglionosis in infants. J Pediatr Surg 38:25–28
Reyes J, Mazariegos GV, Bond GJ et al (2002) History of pediatric organ transplantation. Pediatric intestinal transplantation: historical note, principles and controversies. Pediatr Transplant 6:193–207
Gupte GL, Beath SV, Protheroe S et al (2007) Improved outcome of referrals for intestinal transplantation in UK. Arch Dis Child 92:147–152
Yann R, Yves A, Dominique J et al (2003) Improved quality of life by combined transplantation in Hirschsprung’s disease with a very long aganglionic segment. J Pediatr Surg 38:422–424
Tzakis AG, Nour B, Reyes J et al (1995) Endorectal pull-through of transplanted colon as part of intestinal transplantation. Surgery 117:451–453
Bueno J, Ohwada S, Kocoshis S et al (1999) Factors impacting the survival of children with intestinal failure referred for intestinal transplantation. J Pediatr Surg 34:27–33
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ruttenstock, E., Puri, P. A meta-analysis of clinical outcome in patients with total intestinal aganglionosis. Pediatr Surg Int 25, 833–839 (2009). https://doi.org/10.1007/s00383-009-2439-2
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00383-009-2439-2