eMedicine Specialties > Gastroenterology > Liver

Crigler-Najjar Syndrome: Treatment & Medication

Author: Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Coauthor(s): Mohamed Othman, MD, Staff Physician, Department of Internal Medicine, University of New Mexico School of Medicine; Alessio Pigazzi, MD, PhD, Head, Minimally Invasive Surgery Program, Division of Surgery, Department of General Oncologic Surgery, City of Hope National Medical Center; Jack Bragg, DO, FACOI, Assistant Professor, Department of Clinical Medicine, University of Missouri School of Medicine; Gautam Dehadrai, MD, Consulting Staff, Section Chief, Department of Interventional Radiology, Veterans Affairs Medical Center, Albuquerque
Contributor Information and Disclosures

Updated: Aug 8, 2006

Treatment

Medical Care

Patients with type 2 CNS may not require any treatment or can be managed with phenobarbital. By contrast, prompt treatment of kernicterus is required in patients with type 1 CNS to avoid the potentially devastating neurological sequelae.

  • Emergent management of bilirubin encephalopathy involves plasma exchange transfusion, which acts by removing the bilirubin-saturated albumin and provides free protein, which draws bilirubin from the tissues.
  • Plasma exchange should be accompanied by long-term phototherapy, which helps in the conversion of bilirubin to more soluble isoforms that can be excreted in the urine. Oral calcium phosphate may be a useful adjuvant to phototherapy in type 1 CNS.
  • Therapies based on gene and cell transfer techniques, although largely experimental at the present time, are likely to play an important role in the management of CNS in the future.
  • Inhibitors of heme oxygenase, such as tin protoporphyrin or tin-mesoporphyrin, may be helpful in reducing bilirubin levels emergently, but the effect is short-lived.

Surgical Care

Liver transplantation has been attempted in select patients with type 1 CNS and has achieved good success rates.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Barbiturates

Used to avoid potentially devastating neurological sequelae in type 1 CNS and for the management of neurological symptoms in type 2 CNS.


Phenobarbital (Luminal, Barbita)

Interferes with the transmission of impulses from the thalamus to the cerebral cortex.

Adult

30-120 mg PO/IV bid/tid

Pediatric

3-6 mg/kg/d PO/IV

Coadministration with alcohol may produce additive central nervous system effects and death; chloramphenicol and MAOIs may increase its effect; MAOIs may enhance sedative effects of barbiturates; may decrease chloramphenicol effects; rifampin may decrease its effect; valproic acid appears to decrease barbiturate metabolism and increase toxicity; barbiturates can decrease effects of anticoagulants, and patients stabilized on anticoagulants may require dose adjustments if barbiturates are added to or withdrawn from their regimen; may decrease serum carbamazepine levels; decreased effect of contraceptives may occur because of induction of microsomal enzymes; in women, menstrual irregularities and pregnancy may occur; barbiturates may decrease corticosteroid effects by inducing hepatic microsomal enzymes; barbiturates may increase digitoxin metabolism; may decrease antimicrobial effects of metronidazole; barbiturates decrease theophylline levels possibly resulting in decreased effectiveness; may decrease
bioavailability of verapamil

Documented hypersensitivity, severe respiratory disease, marked impairment of liver function, patients with nephritis

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

During prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; exercise caution in the presence of fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis, myxedema, and depression; may be habit forming

More on Crigler-Najjar Syndrome

Overview: Crigler-Najjar Syndrome
Differential Diagnoses & Workup: Crigler-Najjar Syndrome
Treatment & Medication: Crigler-Najjar Syndrome
Follow-up: Crigler-Najjar Syndrome
References
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References

  1. Arias IM, Gartner LM, Cohen M. Chronic nonhemolytic unconjugated hyperbilirubinemia with glucuronyl transferase deficiency. Clinical, biochemical, pharmacologic and genetic evidence for heterogeneity. Am J Med. Sep 1969;47(3):395-409. [Medline].

  2. Costa E. Hematologically important mutations: bilirubin UDP-glucuronosyltransferase gene mutations in Gilbert and Crigler-Najjar syndromes. Blood Cells Mol Dis. Jan-Feb 2006;36(1):77-80.

  3. Gupta R, Parashar Y. Crigler-najjar syndrome type II. Indian J Pediatr. Nov 2004;71(11):1043.

  4. Jansen PL. Genetic diseases of bilirubin metabolism: the inherited unconjugated hyperbilirubinemias. J Hepatol. Sep 1996;25(3):398-404. [Medline].

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

  6. Lucey JF, Suresh GK, Kappas A. Crigler-Najjar syndrome, 1952-2000: learning from parents and patients about a very rare disease and using the internet to recruit patients for studies. Pediatrics. May 2000;105(5):1152-3. [Medline].

  7. Nowicki MJ, Poley JR. The hereditary hyperbilirubinaemias. Baillieres Clin Gastroenterol. Jun 1998;12(2):355-67. [Medline].

  8. Owens IS, Basu NK, Banerjee R. UDP-glucuronosyltransferases: gene structures of UGT1 and UGT2 families. Methods Enzymol. 2005;400:1-22.

  9. Petit FM, Gajdos V, Francoual J. Allelic heterogeneity of Crigler-Najjar type I syndrome: a study of 24 cases. Clin Genet. Dec 2004;66(6):571-2.

  10. Sampietro M, Iolascon A. Molecular pathology of Crigler-Najjar type I and II and Gilbert''s syndromes. Haematologica. Feb 1999;84(2):150-7.

  11. Servedio V, d''Apolito M, Maiorano N. Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation. Hum Mutat. Mar 2005;25(3):325.

  12. Shevell MI, Majnemer A, Schiff D. Neurologic perspectives of Crigler-Najjar syndrome type I. J Child Neurol. Jun 1998;13(6):265-9.

  13. Sleisenger MH, Fordtran JS. Gastrointestinal Disease. Philadelphia, Pa:. WB Sanders Company;1993:Chapter 85.

  14. Takeuchi K, Kobayashi Y, Tamaki S. Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert''s syndrome as well as in healthy Japanese subjects. J Gastroenterol Hepatol. Sep 2004;19(9):1023-8.

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Further Reading

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Keywords

CNS, Crigler-Najjar disease, Gilbert syndrome, Arias syndrome, congenital nonhemolytic jaundice, neonatal jaundice, inherited unconjugated hyperbilirubinemias, uridine diphosphate glycosyltransferase, UGT, kernicterus, bilirubin encephalopathy, plasma exchange transfusion

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Contributor Information and Disclosures

Author

Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Praveen K Roy, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and Canadian Association of Gastroenterology
Disclosure: Nothing to disclose.

Coauthor(s)

Mohamed Othman, MD, Staff Physician, Department of Internal Medicine, University of New Mexico School of Medicine
Disclosure: Nothing to disclose.

Alessio Pigazzi, MD, PhD, Head, Minimally Invasive Surgery Program, Division of Surgery, Department of General Oncologic Surgery, City of Hope National Medical Center
Disclosure: Nothing to disclose.

Jack Bragg, DO, FACOI, Assistant Professor, Department of Clinical Medicine, University of Missouri School of Medicine
Jack Bragg, DO, FACOI is a member of the following medical societies: American College of Osteopathic Internists and American Osteopathic Association
Disclosure: Nothing to disclose.

Gautam Dehadrai, MD, Consulting Staff, Section Chief, Department of Interventional Radiology, Veterans Affairs Medical Center, Albuquerque
Gautam Dehadrai, MD is a member of the following medical societies: American College of Radiology, Medical Council of India, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Tushar Patel, MD, Associate Professor, Department of Internal Medicine, Texas A&M College of Medicine
Tushar Patel, MD is a member of the following medical societies: American Association for the Study of Liver Diseases and American Gastroenterological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

BS Anand, MD, Department of Internal Medicine, Division of Gastroenterology, Professor, Baylor University College of Medicine
BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Assistant Dean for Medical Curriculum, Associate Professor of Medicine, Division of General Internal Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

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