Alagille syndrome: Review of 14 patients
Abstract
Alagille syndrome (AGS) Is a common form of familial intrahepatic choleslasis, an autosomal dominant disorder due to defects in Jagged1 gene. It Is characterized by at least 3 of 5 mator features. We reviewed two groups of patients with AGS. Group 1 comprised 12 AGS patients, retrospectively studied (1995-1996), in the Gastroenterology Department, Royal Children's Hospital, Melbourne. Group 2 comprised 2 AGS patients, prospectively studied since 1999, in The Pediatric Hepatology Division, Cipto Mangunkusumo Hospital, Jakarta. Prolonged cholestasis is the most common feature at presentation (12 patients). All these 12 subjects developed pruritus and xanthoma of varying degree. Osteopenia occured in 6 patients, 2 patients experienced fractures. AGS facies was noted In aH 14 subjects. Heart anomaty was found in 10 patients, vertebral anomaly in 6 patients, and posterior embryotoxin in 10 patients. Common additional features were growth and mental retardation in 10 and 8 patients, respectively. Liver biopsy was able to confirm the diagnosis as young as age 2 months. Death occurred in 2 patients due to liver failure and hemorrhagic pneumonia. Liver transplant was done in 1 patient due to poor quality of life (severe pruritus, xanthoma, recurrent fractures). Affected family members were strongly presumed in 8 patients. In conclusion, AGS should be considered in babies with chronic Intrahepatic cholestasls, especially it associated with pruritus. Liver biopsy Is the most sensitive diagnostic testing which will prevent unnecessary surgical intervention due to biliary atresia mimicry.
References
2. AtagHie D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, mental and sexual development, and cardiac murmur. J Pediatr. 1975;86:63-8.
3. Watson GH. Miller V. Artenohepatic dysplasia, familial pulmonary atresial stenosis with neonatal liver disease. Arch Dis Child. 1973;480459-66.
4. Alagille D, Estrada A. Hadchouel M, et al. Syndromic Paucity of interlobular bile ducts: Review of 80 patients. J Pediatr. 1987;110:195-200.
5. Riely CA. Familial intrahepatic cholestasis syndrome. Semin liver Dis. 1987;7:119-33.
6. Poley JR. Syndromes of neonatal cholestasis. In: Gracey M, Burke V, editors. Pediatric gastroenterology and hepatology. 3rd ed. Boston: Blackwell Scientific Publications; 1993. p.556-92.
7. Mowatt AP. Hepatitis and cholestasis in infancy: Intrahepatic disorders. In: Mowatt Ap, editor. Liver disorders in childhood. 3rd ed. Oxford Butterworth Heinemann; 1994. p.59-73.
8. Tunessen D. Denouncement and discussion. Alagille syndrome (arteriohepatic dysplasia). Arch Pcdiatr Adolesc Med. 1994; 148:288.
9. Desmaze C, Deleuze JF, Dutrilaux AM, Thomas G, Hadchouel M, Aurias A. Screening of microdeletions of chromosome 20 in patients with Alagille syndrome. J Moo Genet. 1992;29:233-5.
10. Mueller RF, Pagon RA. Pepin M G. Haas JE. Kawabori I. Stevenson JG. Areriohepaticdysplasia: Phenotypic features and family studies. Clin Genetics. 1984;19:323-31.
11. Shulman SA, Hyams JS, Gunta R. Arteriohepatic dysplasia (Alagille syndrome): Extreme variability among affected family members. Am J Med Genet. 1984; 19:325-32.
12. Riely CA. Ctlier E. Jensen PS, Klatskin G. Arteriohepatic dysplasia; A benign syndrome of intrahepatic cholestasis with multiple organ involvement. Ann Intern Med. 1979;91:520-7.
13. Byrne JLB, Harrod MJE, Friedman JM, Howard Peebles PN. DeI(2Op) with manifestations of arteriohepatic dysplasia. Am J Med Genet. 1986; 24: 673-8.
14. Crosnier C, Driancourt C, Raynaud N, Dhorne-Pollet S, Pollet N, Bernard 0, et al. Mutations in JAGGED I gene are predominantly sporadic in Alagille syndrome. Gastroenterology. 1999; 116:1141-8.
15. Zhang F, Deleuze IF, Aurias A, Dutriliaux AM, Hugon RN, Alagille D, et al. lnterstitial deletion of the short ann of chromosome 20 in arteriohepatic dysplasia (Alagille syndrome). J Pediatr. 1990;116:73-7.
16. Dhome-Pollet S, Deleoze IF, Hadchouel M, Bonaiti, Pellie C. Segregation analysis of Alagille syndrome. J Med Genet. 1994;31:453-7.
17. Schnittger S, Hofen C, Heidelmann P, et al. Molecular and cytogenetic analysis of an interstitial 20p deletion associated with syndromic intrahepatic ductular hypoplasia (Alagille syndrome). Hum Genet. 1989;83:239-44.
18. Anad F Bum J, Matthews D, Cross I, Davison BCC, Mueller R, et al. Alagille syndrome and deletion of 20p. J Med Genet. 1990;27:729-37.
19. Schmikel RD. Contiguous gene syndromes: A component of a recognize syndromes. Medical progress. J Pediatr. 1986;109:231-40.
20. Oda T, Elkahloun AG, Meltzer PS,Chandrnsekharappa SC. Identification and cloning of the human homolog (JAGLl) of the rat jagged gene from the Alagille syndrome critical region at 20p 12. Genomics. 1997;43:376-9.
21. Krantz ID, Colliton RP, Geoin A, Rand EB, Li L, Piccoli DA, Spinner NB. Spectrum and frequency of jagged I (JAG I) mutations in Alagille syndrome patients and their families. Am J Hum Genet. 1998;62: 1361-9.
22. Silengo M, Bell GL, Biagioli M, Franceshini P. Partial deletion of the short arm of chromosome 20:46, XX, del (20) (pl1 )/46,XX,mocaicism. Clin Genet. 1988;33:108-10.
23. Wells KK, Pulido JS, Judisch GF, Ossoinig KC, Fisher TC, LaBreque DR. Ophthalmic features of Alagille syndrome (arteriohepatic dysplasia). J Pediatr Opthalmol Strabismus. 1993;30:130-5.
24. Rodriguez JL, Rivera T, Palacios J. Alagille syndrome associated with caudal dysplasia sequence. Am J Med Genet. 1991;40:61-4.
25. Bucuvalas JC, Hom JA, Carisson L, Balistreri WE, Chemausck SD. Growth hormone insensitivity associated with elevated circulating growth hormone binding protein in children with Alagille syndrome and short stature. J Am Endocrinol Metab. 1993;76:1477-82.
26. Berman MD, Ishak KG, Schaefer EJ, et al. Syndromatic hepatic ductular hypoplasia (arteriohepatic dysplasia). A clinical and hepatic histology study of three patients. Dig Dis Sci, 1981;26:485-97.
27. Alpan G, Glick B, Peleg 0, Eyal F. Pseudotumor cerebri and coma in vitamin D dependent rickets. Clin Pediatr. 1991;30:254-6.
28. DeJong AR, Callahan CA, Weiss J. Pseudotumor cerebri and nutritional rickerts. Bur J Pediatr. 1985; 143:219-20.
29. Hoffenberg EJ, Narkewicz MR, Sondheimer JM, et al. Outcome of syndromic paucity of interlobular duct with onset of cholestasis in infancy. J Pediatr. 1995; 127:220-4.
30. Tzakis AG, Reyes J. Tepetes K, et al. Liver transplantation for Alagille syndrome. Arch Surg. 1993;129:337-9.
31. Kaufman SS, Wood RP, Shaw BW. et al. Hepatocarcinoma in a child with the Alagille syndrome. AJDC 1987;141:698-700.
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Accepted 2017-02-08
Published 2017-02-08
