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Crigler-Najjar syndrome

MedGen UID:
1789261
•Concept ID:
C5551003
•
Disease or Syndrome
Synonyms: Crigler Najar Syndrome; Crigler Najjar Syndrome; Crigler Najjar Syndromes; Crigler-Najar Syndrome; Crigler-Najjar Syndrome; Familial Nonhemolytic Unconjugated Hyperbilirubinemia; Hereditary Unconjugated Hyperbilirubinemia; Hereditary Unconjugated Hyperbilirubinemias; Hyperbilirubinemia, Hereditary Unconjugated; Najjar Syndrome, Crigler; Syndrome, Crigler Najjar; Unconjugated Hyperbilirubinemia, Hereditary
SNOMED CT: Crigler-Najjar syndrome (28259009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Related gene: UGT1A1
 
Monarch Initiative: MONDO:0009044
OMIM®: 218800
Orphanet: ORPHA205

Definition

Crigler-Najjar syndrome type I is a potentially lethal disorder characterized by markedly elevated serum concentrations of unconjugated bilirubin, which may lead to brain damage (kernicterus) (summary by Bosma et al., 1992). [from OMIM]

Professional guidelines

PubMed

Disease burden and management of Crigler-Najjar syndrome: Report of a world registry.
Aronson SJ, Junge N, Trabelsi M, Kelmemi W, Hubert A, Brigatti KW, Fox MD, de Knegt RJ, Escher JC, Ginocchio VM, Iorio R, Zhu Y, Özçay F, Rahim F, El-Shabrawi MHF, Shteyer E, Di Giorgio A, D'Antiga L, Mingozzi F, Brunetti-Pierri N, Strauss KA, Labrune P, Mrad R, Baumann U, Beuers U, Bosma PJ; CureCN Consortium
Liver Int 2022 Jul;42(7):1593-1604. Epub 2022 Mar 29 doi: 10.1111/liv.15239. PMID: 35274801
Diagnostic criteria and contributors to Gilbert's syndrome.
Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC
Crit Rev Clin Lab Sci 2018 Mar;55(2):129-139. Epub 2018 Feb 1 doi: 10.1080/10408363.2018.1428526. PMID: 29390925
Diagnosis and management of Crigler-Najjar syndrome.
Jansen PL
Eur J Pediatr 1999 Dec;158 Suppl 2:S89-94. doi: 10.1007/pl00014330. PMID: 10603107

Recent clinical studies

Etiology

Therapeutic Options for Crigler-Najjar Syndrome: A Scoping Review.
Sambati V, Laudisio S, Motta M, Esposito S
Int J Mol Sci 2024 Oct 13;25(20) doi: 10.3390/ijms252011006. PMID: 39456788Free PMC Article
Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives.
Dhawan A, Lawlor MW, Mazariegos GV, McKiernan P, Squires JE, Strauss KA, Gupta D, James E, Prasad S
J Gastroenterol Hepatol 2020 Apr;35(4):530-543. Epub 2019 Oct 24 doi: 10.1111/jgh.14853. PMID: 31495946
Diagnostic criteria and contributors to Gilbert's syndrome.
Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC
Crit Rev Clin Lab Sci 2018 Mar;55(2):129-139. Epub 2018 Feb 1 doi: 10.1080/10408363.2018.1428526. PMID: 29390925
Understanding neonatal hyperbilirubinaemia in the era of genomics.
Watchko JF, Daood MJ, Biniwale M
Semin Neonatol 2002 Apr;7(2):143-52. doi: 10.1053/siny.2002.0102. PMID: 12208099
Genes for jaundice.
Hardikar W
J Paediatr Child Health 1999 Dec;35(6):522-4. doi: 10.1046/j.1440-1754.1999.00431.x. PMID: 10620165

Diagnosis

Diagnostic criteria and contributors to Gilbert's syndrome.
Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC
Crit Rev Clin Lab Sci 2018 Mar;55(2):129-139. Epub 2018 Feb 1 doi: 10.1080/10408363.2018.1428526. PMID: 29390925
Inherited disorders of bilirubin clearance.
Memon N, Weinberger BI, Hegyi T, Aleksunes LM
Pediatr Res 2016 Mar;79(3):378-86. Epub 2015 Nov 23 doi: 10.1038/pr.2015.247. PMID: 26595536Free PMC Article
Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome).
Strassburg CP
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):555-71. doi: 10.1016/j.bpg.2010.07.007. PMID: 20955959
Vigintiphobia revisited.
Watchko JF
Pediatrics 2005 Jun;115(6):1747-53. doi: 10.1542/peds.2004-1748. PMID: 15930239
Hepatocyte transplantation.
Fox IJ, Chowdhury JR
Am J Transplant 2004;4 Suppl 6:7-13. doi: 10.1111/j.1600-6135.2004.0340.x. PMID: 14871269

Therapy

Gene Therapy in Patients with the Crigler-Najjar Syndrome.
D'Antiga L, Beuers U, Ronzitti G, Brunetti-Pierri N, Baumann U, Di Giorgio A, Aronson S, Hubert A, Romano R, Junge N, Bosma P, Bortolussi G, Muro AF, Soumoudronga RF, Veron P, Collaud F, Knuchel-Legendre N, Labrune P, Mingozzi F
N Engl J Med 2023 Aug 17;389(7):620-631. doi: 10.1056/NEJMoa2214084. PMID: 37585628
Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome).
Strassburg CP
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):555-71. doi: 10.1016/j.bpg.2010.07.007. PMID: 20955959
Vigintiphobia revisited.
Watchko JF
Pediatrics 2005 Jun;115(6):1747-53. doi: 10.1542/peds.2004-1748. PMID: 15930239
Hepatocyte transplantation.
Fox IJ, Chowdhury JR
Am J Transplant 2004;4 Suppl 6:7-13. doi: 10.1111/j.1600-6135.2004.0340.x. PMID: 14871269
Neonatal jaundice.
Scheig R
Am Fam Physician 1974 Oct;10(4):158-64. PMID: 4414786

Prognosis

Gene Therapy in Patients with the Crigler-Najjar Syndrome.
D'Antiga L, Beuers U, Ronzitti G, Brunetti-Pierri N, Baumann U, Di Giorgio A, Aronson S, Hubert A, Romano R, Junge N, Bosma P, Bortolussi G, Muro AF, Soumoudronga RF, Veron P, Collaud F, Knuchel-Legendre N, Labrune P, Mingozzi F
N Engl J Med 2023 Aug 17;389(7):620-631. doi: 10.1056/NEJMoa2214084. PMID: 37585628
Successful pregnancy in a Crigler-Najjar type I patient treated by phototherapy and semimonthly albumin infusions.
Gajdos V, Petit F, Trioche P, Mollet-Boudjemline A, Chauveaud A, Myara A, Trivin F, Francoual J, Labrune P
Gastroenterology 2006 Sep;131(3):921-4. doi: 10.1053/j.gastro.2006.07.005. PMID: 16952560
Vigintiphobia revisited.
Watchko JF
Pediatrics 2005 Jun;115(6):1747-53. doi: 10.1542/peds.2004-1748. PMID: 15930239
The familial unconjugated hyperbilirubinemias.
Semin Liver Dis 1994 Nov;14(4):356-85. doi: 10.1055/s-2007-1007328. PMID: 7855631
Crigler-Najjar syndrome: an unusual course with development of neurologic damage at age eighteen.
Blaschke TF, Berk PD, Scharschmidt BF, Guyther JR, Vergalla JM, Waggoner JG
Pediatr Res 1974 May;8(5):573-90. doi: 10.1203/00006450-197405000-00006. PMID: 4825526

Clinical prediction guides

Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier.
Strauss KA, Ahlfors CE, Soltys K, Mazareigos GV, Young M, Bowser LE, Fox MD, Squires JE, McKiernan P, Brigatti KW, Puffenberger EG, Carson VJ, Vreman HJ
Hepatology 2020 Jun;71(6):1923-1939. Epub 2020 Feb 5 doi: 10.1002/hep.30959. PMID: 31553814Free PMC Article
Treatment of Crigler-Najjar Syndrome type 1 by hepatic progenitor cell transplantation: a simple procedure for management of hyperbilirubinemia.
Khan AA, Parveen N, Mahaboob VS, Rajendraprasad A, Ravindraprakash HR, Venkateswarlu J, Rao P, Pande G, Narusu ML, Khaja MN, Pramila R, Habeeb A, Habibullah CM
Transplant Proc 2008 May;40(4):1148-50. doi: 10.1016/j.transproceed.2008.03.022. PMID: 18555136
Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.
Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR
Hum Mutat 2000 Oct;16(4):297-306. doi: 10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z. PMID: 11013440
Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man.
Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RP, Chowdhury JR, Chowdhury NR, Jansen PL
J Biol Chem 1994 Jul 8;269(27):17960-4. PMID: 8027054
Human UDP-glucuronosyl transferases: chemical defence, jaundice and gene therapy.
Brierley CH, Burchell B
Bioessays 1993 Nov;15(11):749-54. doi: 10.1002/bies.950151108. PMID: 8292005

Recent systematic reviews

Disease burden of Crigler-Najjar syndrome: Systematic review and future perspectives.
Dhawan A, Lawlor MW, Mazariegos GV, McKiernan P, Squires JE, Strauss KA, Gupta D, James E, Prasad S
J Gastroenterol Hepatol 2020 Apr;35(4):530-543. Epub 2019 Oct 24 doi: 10.1111/jgh.14853. PMID: 31495946
Pregnancy outcome in maternal Crigler-Najjar syndrome type II: a case report and systematic review of the literature.
Passuello V, Puhl AG, Wirth S, Steiner E, Skala C, Koelbl H, Kohlschmidt N
Fetal Diagn Ther 2009;26(3):121-6. Epub 2009 Sep 11 doi: 10.1159/000238122. PMID: 19752526

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