Type I Crigler Najjar Syndrome In Tunisia: A Study Of 30 Cases

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Published Sep 30, 2010
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Vol. 88 No. 10 (2010): Issue Oct 2010

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hajer Aloulou
Afef Ben Thabet
Sonia Khanfir
Lamia Ben Mansour
Imen Chabchoub
Phillipe Labrune
Thouraya Kammoun
Mongia Hachicha

Abstract

Background : Crigler-Najjar syndrome is a rare metabolic disorder characterized by severe unconjugated hyperbilirubinemia resulting in deficiency of bilirubin uridine diphosphate (UDP) glucuronosyltransferase activity in the liver.
Aim : To study the clinical, genetic therapeutic aspects and the outecome of Crigler Najjar type 1 in Tunisia.
Methods: This is a retrospective report of Crigler Najjar cases who were hospitalised in pediatric department of Hédi Chaker hospital during 21 years (from 1st January to 31 December 2006).
Results: Our study included 30 cases of Crigler-Najjar syndrome; there were 10 females and 20 males (sex ratio = 2). The mean age of our patients was 41 days (4 days - 9 months). All patients were presented with intense jaundice. Sixteen patients had neurologic disorders since admission. Genetic analysis was performed in 9 patients; we identified the same mutation in all cases: -C1070>G in exon 3 of the UDP glucuronyl transferase. Concerning therapeutic measurements, conventional phototherapy was used in all patients. A fatal out come was observed in 28 case; they died of kernicterus.
Conclusion: Crigler-Najjar syndrome is a serious disorder which, when not treated, ultimately leads to brain damage (bilirubin encephalopathy) and death. That’s why we must promote prenatal diagnosis and genetic council especially because of the big frequency of consanguinity in our country.

Keywords:

Crigler Najjar syndrome, child, phototherapy, liver transplantation, kernicterus

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References

  1. Fitouri Z., Barhoumi N., Debbabi R., et al Maladie de Crigler Najjar à propos de 8 cas. Rev Maghr pédiatr, 2002 : 297- 301
  2. Tabarki B., KhalifaM., Yacoub.M., et al Cerebellar symptoms hearding bilirubinencéphalopathy in Crigler Najjar syndrome. Pediatr neurol, 2002; 27: 234-236
  3. Petit FM, Béziau. S, Gajdos.V, et al. The Tunisian population history through the Crigler Najjar syndrome. Eur J Hum Genet. 2008.16: 848-53
  4. Bosma P.J Inherited disorders of bilirubin metabolism. J hepatol, 2003;38:107-117.
  5. Kappas A., Drummond G.S., Manola T. et al Direct comparison of Snmesoporphyrin, an inhibitor of bilirubin production and phototherapy in controlling hyperbilirubinémia in term and near term newborns. Pediatrics, 1995; 95: 468- 497
  6. Valeas T., Petmezaki S., Henschke C., et al. Control of jaundice in preterm newborns by an inhibitor of bilirubin production: studies with Tin - mesoporphyrin. Pediatrics, 1994; 93: 1-11
  7. Lachaux A., Eid B., Stamm D. et al. La transplantation hépatique chez le nourrisson et líenfant à propos de 40 observations. Arch pédiatr, 2000 ; 7 : 369-376.
  8. Shauer R., Stangl M., Lang T., et al. Treatment of Crigler Najjar type 1: relevance of early liver transplantation. J pediatr surg, 2003; 38: 1227-1231.
  9. Griedelli B., LucianettiA., Gatti S., et al. Orthotopic liver transplantation for Crigler Najjar type I syndrome. Transplant proc, 1997; 29: 440- 441.
  10. Al Shurafa H., Wali S., Chehab M.S et al. Living related liver transplantation for Crigler Najjar syndrome in Saudi Arabia. Clin transplant, 2002; 16: 222- 226
  11. Dhawan A, Mitry RR, Hughes RD et al. Hépatocyte transplantation for liverbased metabolic disorders. J Inherit Metab Dis. 2006; 29:431-5
  12. Fox IJ, Chowdhury J R, Kauffman SS et al. Treatement of the Crigler Najjar syndrome type I with hepatocyte transplantation. N Engl J Med 1998; 338 : 1422-6
  13. Roy-Chowdhury N, Kadakol A, Sappal BS et al. Gene therapy for inherited hyperbilirubinemias. J Perinatol.2001; 21: S114-8
  14. Bellodi-Privato M, Aubert D, Pichard V, Myara A, Trivin F, Ferry N. Successful gene therapy of the Gunn rat by in vivo neonatal hepatic gene transfer using murine oncoretroviral vectors. Hepatology. 2005;42:431-8
  15. Kaplan M., Hammerman C. Understanding severe hyperbilirubinemia and preventing kernicterus: adjuncts in interpretation of neonatal serum bilirubin. Clin Chim Acta, 2005; 356: 9-21
  16. Shapiro S.M. Bilrubin toxicity in the developing nervous system. Pediatr neurol, 2003; 29: 410- 421.
  17. Strauss KA, Robinson DL, Vreman HJ et coll. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler- Najjar disease. Eur J Pediatr, 2006 ; 165:306-19