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Crigler-Najjar syndrome, type II(HBLRCN2)

MedGen UID:
419718
Concept ID:
C2931132
Disease or Syndrome
Synonyms: Crigler Najjar syndrome, type 2; HYPERBILIRUBINEMIA, CRIGLER-NAJJAR TYPE II; Mutation in the UDP-glucuronosyl-transferase gene
SNOMED CT: Crigler-Najjar syndrome, type II (68067009); Crigler-Najjar syndrome type II (68067009); Crigler-Najjar type 2 (68067009); Arias syndrome (68067009)
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).
 
Gene (location): UGT1A1 (2q37.1)
 
Monarch Initiative: MONDO:0011725
OMIM®: 606785
Orphanet: ORPHA79235

Definition

The hereditary hyperbilirubinemias include (1) those resulting in predominantly unconjugated hyperbilirubinemia: Gilbert or Arias syndrome, Crigler-Najjar syndrome type I, and Crigler-Najjar syndrome type II; and (2) those resulting in predominantly conjugated hyperbilirubinemia: Dubin-Johnson syndrome (237500), Rotor syndrome (237450), and several forms of intrahepatic cholestasis (147480, 211600, 214950, 243300) (Wolkoff et al., 1983). Detailed studies show that patients with Crigler-Najjar syndrome type II have reduced activity of bilirubin glucuronosyltransferase (Labrune et al., 1989, Seppen et al., 1994). [from OMIM]

Additional description

From MedlinePlus Genetics
Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice). In Crigler-Najjar syndrome, jaundice is apparent at birth or in infancy. Severe unconjugated hyperbilirubinemia can lead to a condition called kernicterus, which is a form of brain damage caused by the accumulation of unconjugated bilirubin in the brain and nerve tissues. Babies with kernicterus are often extremely tired (lethargic) and may have weak muscle tone (hypotonia). These babies may experience episodes of increased muscle tone (hypertonia) and arching of their backs. Kernicterus can lead to other neurological problems, including involuntary writhing movements of the body (choreoathetosis), hearing problems, or intellectual disability.

Crigler-Najjar syndrome is divided into two types. Type 1 (CN1) is very severe, and affected individuals can die in childhood due to kernicterus, although with proper treatment, they may survive longer. Type 2 (CN2) is less severe. People with CN2 are less likely to develop kernicterus, and most affected individuals survive into adulthood.

Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia).  https://medlineplus.gov/genetics/condition/crigler-najjar-syndrome

Clinical features

From HPO
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Unconjugated hyperbilirubinemia
MedGen UID:
82786
Concept ID:
C0268306
Disease or Syndrome
An increased amount of unconjugated (indirect) bilurubin in the blood.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Reduced tissue UDP-glucuronyl-transferase activity
MedGen UID:
1053323
Concept ID:
CN377449
Finding
Concentration or activity of uridine diphosphate glucuronosyltransferase below the lower limit of normal. The activity of this enzyme can be measured in liver and rarely in other tissues.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Crigler-Najjar syndrome, type II in Orphanet.

Professional guidelines

PubMed

Abuduxikuer K, Fang LJ, Li LT, Gong JY, Wang JS
Medicine (Baltimore) 2018 Dec;97(49):e13576. doi: 10.1097/MD.0000000000013576. PMID: 30544479Free PMC Article
Maruo Y, Nakahara S, Yanagi T, Nomura A, Mimura Y, Matsui K, Sato H, Takeuchi Y
J Gastroenterol Hepatol 2016 Feb;31(2):403-8. doi: 10.1111/jgh.13071. PMID: 26250421

Recent clinical studies

Etiology

Fernandes SR, Moura CM, Rodrigues B, Correia LA, Cortez-Pinto H, Velosa J
BMC Gastroenterol 2016 Mar 11;16:33. doi: 10.1186/s12876-016-0449-9. PMID: 26968162Free PMC Article
Maruo Y, Nakahara S, Yanagi T, Nomura A, Mimura Y, Matsui K, Sato H, Takeuchi Y
J Gastroenterol Hepatol 2016 Feb;31(2):403-8. doi: 10.1111/jgh.13071. PMID: 26250421
Iijima S, Ohzeki T, Maruo Y
Yonsei Med J 2011 Mar;52(2):369-72. doi: 10.3349/ymj.2011.52.2.369. PMID: 21319362Free PMC Article
Yilmaz S, Dursun M, Canoruç F, Kidir V, Beştaş R
Turk J Gastroenterol 2006 Mar;17(1):62-5. PMID: 16830281
Ito T, Katagiri C, Ikeno S, Takahashi H, Nagata N, Terakawa N
J Obstet Gynaecol Res 2001 Feb;27(1):33-5. doi: 10.1111/j.1447-0756.2001.tb01212.x. PMID: 11330728

Diagnosis

Cozzi L, Nuti F, Degrassi I, Civeriati D, Paolella G, Nebbia G
Ital J Pediatr 2022 Apr 18;48(1):59. doi: 10.1186/s13052-022-01251-4. PMID: 35436954Free PMC Article
Liaqat A, Shahid A, Attiq H, Ameer A, Imran M
J Coll Physicians Surg Pak 2018 Oct;28(10):806-808. PMID: 30266131
Sun L, Li M, Zhang L, Teng X, Chen X, Zhou X, Ma Z, Qi L, Wang P
Medicine (Baltimore) 2017 Nov;96(45):e8620. doi: 10.1097/MD.0000000000008620. PMID: 29137095Free PMC Article
Fernandes SR, Moura CM, Rodrigues B, Correia LA, Cortez-Pinto H, Velosa J
BMC Gastroenterol 2016 Mar 11;16:33. doi: 10.1186/s12876-016-0449-9. PMID: 26968162Free PMC Article
Gordon ER, Shaffer EA, Sass-Kortsak A
Gastroenterology 1976 May;70(5 PT.1):761-5. PMID: 1261771

Therapy

Gailite L, Rots D, Pukite I, Cernevska G, Kreile M
BMC Pediatr 2018 Oct 3;18(1):317. doi: 10.1186/s12887-018-1285-6. PMID: 30285761Free PMC Article
Liaqat A, Shahid A, Attiq H, Ameer A, Imran M
J Coll Physicians Surg Pak 2018 Oct;28(10):806-808. PMID: 30266131
Iijima S, Ohzeki T, Maruo Y
Yonsei Med J 2011 Mar;52(2):369-72. doi: 10.3349/ymj.2011.52.2.369. PMID: 21319362Free PMC Article
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
Ito T, Katagiri C, Ikeno S, Takahashi H, Nagata N, Terakawa N
J Obstet Gynaecol Res 2001 Feb;27(1):33-5. doi: 10.1111/j.1447-0756.2001.tb01212.x. PMID: 11330728

Prognosis

Zheng B, Hu G, Yu J, Liu Z
BMC Pediatr 2014 Oct 15;14:267. doi: 10.1186/1471-2431-14-267. PMID: 25319636Free PMC Article
Costa E, Vieira E, Martins M, Saraiva J, Cancela E, Costa M, Bauerle R, Freitas T, Carvalho JR, Santos-Silva E, Barbot J, Dos Santos R
Blood Cells Mol Dis 2006 Jan-Feb;36(1):91-7. Epub 2005 Nov 2 doi: 10.1016/j.bcmd.2005.09.002. PMID: 16269258
Holstein A, Plaschke A, Lohse P, Egberts EH
Scand J Gastroenterol 2005 Sep;40(9):1124-6. PMID: 16211719

Clinical prediction guides

Sun L, Li M, Zhang L, Teng X, Chen X, Zhou X, Ma Z, Qi L, Wang P
Medicine (Baltimore) 2017 Nov;96(45):e8620. doi: 10.1097/MD.0000000000008620. PMID: 29137095Free PMC Article
Li L, Deng G, Tang Y, Mao Q
PLoS One 2015;10(5):e0126263. Epub 2015 May 20 doi: 10.1371/journal.pone.0126263. PMID: 25993113Free PMC Article
Zheng B, Hu G, Yu J, Liu Z
BMC Pediatr 2014 Oct 15;14:267. doi: 10.1186/1471-2431-14-267. PMID: 25319636Free PMC Article
Suzuki M, Hirata M, Takagi M, Watanabe T, Iguchi T, Koiwai K, Maezawa S, Koiwai O
J Hum Genet 2014 Mar;59(3):158-62. Epub 2014 Jan 9 doi: 10.1038/jhg.2013.138. PMID: 24401909Free PMC Article
Yilmaz S, Dursun M, Canoruç F, Kidir V, Beştaş R
Turk J Gastroenterol 2006 Mar;17(1):62-5. PMID: 16830281

Recent systematic reviews

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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