eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Glucuronyl Transferase Deficiency: Differential Diagnoses & Workup

Author: Dena Nazer, MD, Medical Director, Child Protection Center, Children's Hospital of Michigan; Assistant Professor, Wayne State University
Coauthor(s): Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan
Contributor Information and Disclosures

Updated: Jan 11, 2010

Differential Diagnoses

Jaundice, Neonatal

Other Problems to Be Considered

Neonatal jaundice
Breast-mild jaundice
Gilbert syndrome (see Physical)

Workup

Laboratory Studies

No widely available simple clinical test is available to confirm diagnosis of Crigler-Najjar (CN) syndrome.

  • Determination of bilirubin level
    • The unconjugated bilirubin level is elevated, with direct bilirubin less than 15% of the total serum bilirubin. High-performance liquid chromatography analysis of duodenal bile reveals that, in Crigler-Najjar syndrome type 1, negligible bilirubin diglucuronides or monoglucoronides are present; in Crigler-Najjar syndrome type 2, these conjugates are present but in low concentrations. DNA analysis can be very helpful in establishing the correct diagnosis.
    • Persistent unconjugated hyperbilirubinemia levels of more than 20 mg/dL after the first week of life in the absence of liver disease or hemolysis strongly suggests uridinediphosphoglucuronate glucuronosyltransferase (UGT) deficiency.
  • Liver function testing
    • Liver enzyme levels are usually within the reference range.
    • Occasionally, liver enzyme levels may be somewhat elevated as a result of intrahepatic cholestasis.

Procedures

  • Percutaneous liver biopsy
    • Enzymatic assay of liver tissue reveals absent UGT activity in Crigler-Najjar syndrome type 1 and diminished activity in Crigler-Najjar syndrome type 2.
    • Definitive diagnosis of Crigler-Najjar syndrome requires high-performance liquid chromatography of bile or tissue enzyme assay of a liver biopsy sample.

Histologic Findings

  • Liver biopsy reveals normal histology other than the occasional bile plugs in the bile canaliculi.
  • Bile is sometimes observed in the portal triad, in dilated bile canaliculi, in hepatocytes, and in Kupffer cells.
  • Enzymatic assays of the biopsy specimen confirm the almost-absent UGT hepatic activity in Crigler-Najjar syndrome type 1.

More on Glucuronyl Transferase Deficiency

Overview: Glucuronyl Transferase Deficiency
Differential Diagnoses & Workup: Glucuronyl Transferase Deficiency
Treatment & Medication: Glucuronyl Transferase Deficiency
Follow-up: Glucuronyl Transferase Deficiency
Multimedia: Glucuronyl Transferase Deficiency
References
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References

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  2. Nydegger A, Bednarz A, Hardikar W. Use of daytime phototherapy for Crigler-Najjar disease. J Paediatr Child Health. Jul 2005;41(7):387-9. [Medline].

  3. Morioka D, Kasahara M, Takada Y, et al. Living donor liver transplantation for pediatric patients with inheritable metabolic disorders. Am J Transplant. Nov 2005;5(11):2754-63. [Medline].

  4. Bosma PJ, Chowdhury NR, Goldhoorn BG, et al. Sequence of exons and the flanking regions of human bilirubin-UDP- glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. Hepatology. May 1992;15(5):941-7. [Medline].

  5. Toietta G, Mane VP, Norona WS, et al. Lifelong elimination of hyperbilirubinemia in the Gunn rat with a single injection of helper-dependent adenoviral vector. Proc Natl Acad Sci U S A. Mar 15 2005;102(11):3930-5. [Medline].

  6. Jansen PL. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr. Dec 1999;158 Suppl 2:S89-94. [Medline].

  7. Kaplan M, Hammerman C, Maisels MJ. Bilirubin genetics for the nongeneticist: hereditary defects of neonatal bilirubin conjugation. Pediatrics. Apr 2003;111(4 Pt 1):886-93. [Medline].

  8. Sisson TR, Drummond GS, Samonte D, Calabio R, Kappas A. Sn-protoporphyrin blocks the increase in serum bilirubin levels that develops postnatally in homozygous Gunn rats. J Exp Med. Mar 1 1988;167(3):1247-52. [Medline].

  9. Birraux J, Menzel O, Wildhaber B, Jond C, Nguyen TH, Chardot C. A step toward liver gene therapy: efficient correction of the genetic defect of hepatocytes isolated from a patient with Crigler-Najjar syndrome type 1 with lentiviral vectors. Transplantation. Apr 15 2009;87(7):1006-12. [Medline].

  10. Schauer R, Stangl M, Lang T, et al. Treatment of Crigler-Najjar type 1 disease: relevance of early liver transplantation. J Pediatr Surg. Aug 2003;38(8):1227-31. [Medline].

  11. van der Veere CN, Sinaasappel M, McDonagh AF, et al. Current therapy for Crigler-Najjar syndrome type 1: report of a world registry. Hepatology. Aug 1996;24(2):311-5. [Medline].

  12. Ambrosino G, Varotto S, Strom SC, et al. Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1. Cell Transplant. 2005;14(2-3):151-7. [Medline].

  13. Fox IJ, Chowdhury JR. Hepatocyte transplantation. Am J Transplant. 2004;4 Suppl 6:7-13. [Medline].

  14. Lysy PA, Najimi M, Stephenne X, Bourgois A, Smets F, Sokal EM. Liver cell transplantation for Crigler-Najjar syndrome type I: update and perspectives. World J Gastroenterol. Jun 14 2008;14(22):3464-70. [Medline].

  15. Dhawan A, Mitry RR, Hughes RD. Hepatocyte transplantation for liver-based metabolic disorders. J Inherit Metab Dis. Apr-Jun 2006;29(2-3):431-5. [Medline].

  16. Nazer H, Al-Mehaidib A, Shabib S, Ali MA. Crigler-Najjar syndrome in Saudi Arabia. Am J Med Genet. Aug 27 1998;79(1):12-5. [Medline].

  17. Ciotti M, Werlin SL, Owens IS. Delayed response to phenobarbital treatment of a Crigler-Najjar type II patient with partially inactivating missense mutations in the bilirubin UDP-glucuronosyltransferase gene. J Pediatr Gastroenterol Nutr. Feb 1999;28(2):210-3. [Medline].

  18. Costa E, Vieira E, Martins M, Saraiva J, Cancela E, Costa M. Analysis of the UDP-glucuronosyltransferase gene in Portuguese patients with a clinical diagnosis of Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis. Jan-Feb 2006;36(1):91-7. [Medline].

  19. Miranda PS, Bosma PJ. Towards liver-directed gene therapy for crigler-najjar syndrome. Curr Gene Ther. Apr 2009;9(2):72-82. [Medline].

  20. Nazer H, Gunasekaran TS, Sakati NA, Nyhan WL. Concurrence of Robinow syndrome and Crigler-Najar syndrome in two offspring of first cousins. Am J Med Genet. Dec 1990;37(4):516-8. [Medline].

  21. Strauss KA, Robinson DL, Vreman HJ, Puffenberger EG, Hart G, Morton DH. Management of hyperbilirubinemia and prevention of kernicterus in 20 patients with Crigler-Najjar disease. Eur J Pediatr. May 2006;165(5):306-19. [Medline].

  22. Vitek L, Muchova L, Zelenka J, et al. The effect of zinc salts on serum bilirubin levels in hyperbilirubinemic rats. J Pediatr Gastroenterol Nutr. Feb 2005;40(2):135-40. [Medline].

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Further Reading

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Keywords

glucuronyl transferase deficiency, Crigler-Najjar disease type 1, Crigler-Najjar syndrome type 2, CN syndrome, Arias syndrome, congenital nonhemolytic jaundice, inherited unconjugated hyperbilirubinemias, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Dena Nazer, MD, Medical Director, Child Protection Center, Children's Hospital of Michigan; Assistant Professor, Wayne State University
Dena Nazer, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, and Helfer Society
Disclosure: Nothing to disclose.

Coauthor(s)

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan
Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H is a member of the following medical societies: Royal College of Paediatrics and Child Health, Royal College of Physicians, Royal College of Surgeons in Ireland, Royal College of Surgeons of Edinburgh, and Royal Society of Tropical Medicine and Hygiene
Disclosure: Nothing to disclose.

Medical Editor

Jayant Deodhar, MD, Associate Professor in Pediatrics, BJ Medical College, India; Honorary Consultant, Departments of Pediatrics and Neonatology, King Edward Memorial Hospital, India
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

David A Piccoli, MD, Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine
David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, and North American Society for Pediatric Gastroenterology and Nutrition
Disclosure: Nothing to disclose.

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNY-Downstate Medical Center
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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