MCID: CRG004
MIFTS: 49

Crigler-Najjar Syndrome, Type Ii

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Liver diseases

Aliases & Classifications for Crigler-Najjar Syndrome, Type Ii

MalaCards integrated aliases for Crigler-Najjar Syndrome, Type Ii:

Name: Crigler-Najjar Syndrome, Type Ii 53 49 28 13 51
Crigler Najjar Syndrome, Type 2 49 69
Bilirubin Uridinediphosphate Glucuronosyltransferase Deficiency Type 2 55
Hyperbilirubinemia, Crigler-Najjar Type Ii; Hblrcn2 53
Hereditary Unconjugated Hyperbilirubinemia Type 2 55
Hyperbilirubinemia, Crigler-Najjar Type Ii 53
Bilirubin-Ugt Deficiency Type 2 55
Crigler-Najjar Syndrome Type Ii 71
Crigler-Najjar Syndrome Type 2 55
Crigler-Najjar Syndrome 2 71
Ugt Deficiency Type 2 55
Arias Syndrome 55
Hblrcn2 53
Cn-Ii 71
Cn2 71

Characteristics:

Orphanet epidemiological data:

55
crigler-najjar syndrome type 2
Inheritance: Autosomal recessive; Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
uncommon disorder
decreased bilirubin concentration with phenobarbital administration
see also crigler-najjar syndrome type i which is also due to mutations in ugt1


HPO:

31
crigler-najjar syndrome, type ii:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 606785
Orphanet 55 ORPHA79235
MESH via Orphanet 42 C536213
UMLS via Orphanet 70 C2931132 C0268311
ICD10 via Orphanet 33 E80.5
UMLS 69 C2931132

Summaries for Crigler-Najjar Syndrome, Type Ii

NIH Rare Diseases : 49 Crigler Najjar syndrome, type 2 is caused by mutations in the UGT1A1 gene. The gene mutation causes the body to be unable to make adequate enzyme to convert bilirubin into a form that can easily be removed from the body. Without this enzyme, bilirubin can build up in the body and lead to extraordinarily yellow skin and eyes (jaundice). This condition is less severe than the type 1 form, however the severity of type II can vary greatly. Almost all patients with Crigler Najjar syndrome, type 2 develop normally, but there is a risk for some neurologic damage from kernicterus (bilirubin accumulation in the brain). In general people with type 2 Crigler Najjar syndrome have serum bilirubin levels ranging from 20 to 45 mg/dL. Phenobarbital treatment is the standard therapy for this condition and can often help to drastically reduce the bilirubin levels. Last updated: 1/19/2011

MalaCards based summary : Crigler-Najjar Syndrome, Type Ii, also known as crigler najjar syndrome, type 2, is related to gilbert syndrome and bilirubin metabolic disorder, and has symptoms including unconjugated hyperbilirubinemia, prolonged neonatal jaundice and neonatal hyperbilirubinemia. An important gene associated with Crigler-Najjar Syndrome, Type Ii is UGT1A1 (UDP Glucuronosyltransferase Family 1 Member A1), and among its related pathways/superpathways are Cytochrome P450 - arranged by substrate type and Drug metabolism - cytochrome P450. The drugs Acetylcholine and abobotulinumtoxinA have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and eye.

OMIM : 53 The hereditary hyperbilirubinemias (Wolkoff et al., 1983) 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). 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). (606785)

UniProtKB/Swiss-Prot : 71 Crigler-Najjar syndrome 2: Patients have less severe hyperbilirubinemia and usually survive into adulthood without neurologic damage. Phenobarbital, which induces the partially deficient glucuronyl transferase, can diminish the jaundice. CN2 inheritance is autosomal dominant.

Related Diseases for Crigler-Najjar Syndrome, Type Ii

Graphical network of the top 20 diseases related to Crigler-Najjar Syndrome, Type Ii:



Diseases related to Crigler-Najjar Syndrome, Type Ii

Symptoms & Phenotypes for Crigler-Najjar Syndrome, Type Ii

Symptoms via clinical synopsis from OMIM:

53
Skin Nails Hair Skin:
jaundice

Laboratory Abnormalities:
hyperbilirubinemia, unconjugated, <20mg/dl
normal serum liver enzymes
decreased or absent udp-glucuronyl-transferase activity


Clinical features from OMIM:

606785

Human phenotypes related to Crigler-Najjar Syndrome, Type Ii:

55 31
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 unconjugated hyperbilirubinemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0008282
2 prolonged neonatal jaundice 55 31 hallmark (90%) Very frequent (99-80%) HP:0006579
3 neonatal hyperbilirubinemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003265
4 jaundice 31 HP:0000952

UMLS symptoms related to Crigler-Najjar Syndrome, Type Ii:


icterus

Drugs & Therapeutics for Crigler-Najjar Syndrome, Type Ii

Drugs for Crigler-Najjar Syndrome, Type Ii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved 51-84-3 187
2 abobotulinumtoxinA
3 Botulinum Toxins
4 Botulinum Toxins, Type A
5 Cholinergic Agents
6 Neuromuscular Agents
7 Neurotransmitter Agents
8 onabotulinumtoxinA
9 Peripheral Nervous System Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Comparison of Biofeedback vs. Botox Injection to Treat Levator Ani Syndrome Unknown status NCT00564707
2 Gastrointestinal Biopsychosocial Research Center Completed NCT00947180
3 A Study Examining the Use of Vaginal Nifedipine With Pelvic Floor Physical Therapy for Levator Myalgia and Pelvic Pain Withdrawn NCT01586286 Nifedipine;Placebo Ointment Base

Search NIH Clinical Center for Crigler-Najjar Syndrome, Type Ii

Genetic Tests for Crigler-Najjar Syndrome, Type Ii

Genetic tests related to Crigler-Najjar Syndrome, Type Ii:

# Genetic test Affiliating Genes
1 Crigler-Najjar Syndrome, Type Ii 28 UGT1A1

Anatomical Context for Crigler-Najjar Syndrome, Type Ii

MalaCards organs/tissues related to Crigler-Najjar Syndrome, Type Ii:

38
Skin, Brain, Eye, Liver

Publications for Crigler-Najjar Syndrome, Type Ii

Articles related to Crigler-Najjar Syndrome, Type Ii:

(show all 34)
# Title Authors Year
1
Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II. ( 29137095 )
2017
2
[Genetic analysis of a child affected with Crigler-Najjar syndrome type II]. ( 27264814 )
2016
3
Acute cholangitis in an old patient with Crigler-Najjar syndrome type II - a case report. ( 26968162 )
2016
4
Spectrum of UGT1A1 Variations in Chinese Patients with Crigler-Najjar Syndrome Type II. ( 25993113 )
2015
5
Genotype of UGT1A1 and phenotype correlation between Crigler-Najjar syndrome type II and Gilbert syndrome. ( 26250421 )
2015
6
Truncated UDP-glucuronosyltransferase (UGT) from a Crigler-Najjar syndrome type II patient colocalizes with intact UGT in the endoplasmic reticulum. ( 24401909 )
2014
7
Crigler-Najjar syndrome type II in a Chinese boy resulting from three mutations in the bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1) gene and a family genetic analysis. ( 25319636 )
2014
8
Molecular Analysis of the UGT1A1 Gene in Korean Patients with Crigler-Najjar Syndrome Type II. ( 24749086 )
2014
9
Role of a homozygous A(TA)a88TAA promoter polymorphism and an exon 1 heterozygous frameshift mutation UGT1A1 in Crigler-Najjar syndrome type II in a Thai neonate. ( 24065680 )
2013
10
Phenotype heterogeneity of hyperbilirubinemia condition: the lesson by coinheritance of glucose-6-phosphate dehydrogenase deficiency and Crigler-Najjar syndrome type II in an Italian patient. ( 22633750 )
2012
11
Hereditary spherocytosis coexisting with UDP-glucuronosyltransferase deficiency highly suggestive of Crigler-Najjar syndrome type II. ( 21319362 )
2011
12
Three consecutive pregnancies in a woman with Crigler-Najjar syndrome type II with good maternal and neonatal outcomes. ( 20843754 )
2011
13
Pregnancy outcome in maternal Crigler-Najjar syndrome type II: a case report and systematic review of the literature. ( 19752526 )
2009
14
Pregnancy with Crigler-Najjar syndrome type II. ( 19358036 )
2009
15
A homozygous mutation in a Chinese man with Crigler-Najjar syndrome type II and a family genetic analysis. ( 18419642 )
2008
16
Gilbert's syndrome phenotypically expressed as Crigler-Najjar syndrome type II. ( 17454871 )
2007
17
Fenofibrate treatment in two adults with Crigler-Najjar syndrome type II. ( 16830281 )
2006
18
Crigler-Najjar syndrome type II caused by a homozygous triple mutation [T-3279G, A(TA)7TAA, and H39D] of UGT1A1. ( 16456422 )
2006
19
Successful photo-and phenobarbital therapy during pregnancy in a woman with Crigler-Najjar syndrome type II. ( 16211719 )
2005
20
Crigler-Najjar syndrome type II in a caucasian patient resulting from two mutations in the bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1) gene. ( 11983459 )
2002
21
Kernicterus in a child with Crigler-Najjar Syndrome Type II. ( 12170921 )
2002
22
Phenobarbital following phototherapy for Crigler-Najjar syndrome type II with good fetal outcome: a case report. ( 11330728 )
2001
23
A novel compound heterozygous variation of the uridine-diphosphoglucuronosyl transferase 1A1 gene that causes Crigler-Najjar syndrome type II. ( 11668224 )
2001
24
Crigler-Najjar syndrome type II resulting from three different mutations in the bilirubin uridine 5'-diphosphate-glucuronosyltransferase (UGT1A1) gene. ( 11182932 )
2000
25
Mutation of UGT1A1 gene in a case of Crigler-Najjar syndrome type II. ( 10364060 )
1999
26
Contribution of two missense mutations (G71R and Y486D) of the bilirubin UDP glycosyltransferase (UGT1A1) gene to phenotypes of Gilbert's syndrome and Crigler-Najjar syndrome type II. ( 9630669 )
1998
27
Analysis of bilirubin uridine 5'-diphosphate (UDP)- glucuronosyltransferase gene mutations in seven patients with Crigler- Najjar syndrome type II. ( 9621515 )
1998
28
Crigler-Najjar syndrome type II is inherited both as a dominant and as a recessive trait. ( 8733132 )
1996
29
Crigler-Najjar syndrome type II. New observation of possible autosomal recessive inheritance. ( 7821116 )
1995
30
Identification of defect in the genes for bilirubin UDP-glucuronosyl- transferase in a patient with Crigler-Najjar syndrome type II. ( 8280139 )
1993
31
A mutation in bilirubin uridine 5'-diphosphate-glucuronosyltransferase isoform 1 causing Crigler-Najjar syndrome type II. ( 8514037 )
1993
32
Crigler-Najjar syndrome type II with kernicterus. ( 3443510 )
1987
33
Effect of phenobarbital on serum and biliary parameters in a patient with Crigler-Najjar syndrome, type II and acquired cholestasis. ( 6872808 )
1983
34
Bilirubin secretion and conjujation in the Crigler-Najjar syndrome type II. ( 1261771 )
1976

Variations for Crigler-Najjar Syndrome, Type Ii

UniProtKB/Swiss-Prot genetic disease variations for Crigler-Najjar Syndrome, Type Ii:

71 (show all 29)
# Symbol AA change Variation ID SNP ID
1 UGT1A1 p.Arg209Trp VAR_007698 rs72551343
2 UGT1A1 p.Gln331Arg VAR_007702 rs72551348
3 UGT1A1 p.Tyr486Asp VAR_007709 rs34993780
4 UGT1A1 p.Gly71Arg VAR_009504 rs4148323
5 UGT1A1 p.Pro229Gln VAR_009505 rs35350960
6 UGT1A1 p.Leu15Arg VAR_019410 rs111033541
7 UGT1A1 p.Leu175Gln VAR_019411 rs72551341
8 UGT1A1 p.Asn400Asp VAR_019412 rs28934877
9 UGT1A1 p.Pro34Gln VAR_026134
10 UGT1A1 p.Val225Gly VAR_026137 rs35003977
11 UGT1A1 p.Ile294Thr VAR_026139 rs72551347
12 UGT1A1 p.Arg336Leu VAR_026140
13 UGT1A1 p.Arg336Trp VAR_026142 rs139607673
14 UGT1A1 p.Trp354Arg VAR_026143
15 UGT1A1 p.His376Arg VAR_026144
16 UGT1A1 p.Gly377Val VAR_026145
17 UGT1A1 p.Arg403Cys VAR_026148 rs778766461
18 UGT1A1 p.Trp461Arg VAR_026149
19 UGT1A1 p.Ala478Asp VAR_026150
20 UGT1A1 p.Ser191Phe VAR_064956
21 UGT1A1 p.Asn279Tyr VAR_064957 rs397978903
22 UGT1A1 p.Ile370Val VAR_064958 rs748989741
23 UGT1A1 p.Pro387His VAR_064959
24 UGT1A1 p.Leu443Pro VAR_064961 rs758411577
25 UGT1A1 p.Tyr230Cys VAR_071403 rs754922685
26 UGT1A1 p.Arg367Cys VAR_071404 rs55750087
27 UGT1A4 p.Gln332Arg VAR_007710 rs72551348
28 UGT1A4 p.Leu132Pro VAR_009506 rs72551337
29 UGT1A4 p.Tyr487Asp VAR_009507 rs34993780

ClinVar genetic disease variations for Crigler-Najjar Syndrome, Type Ii:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 UGT1A1 NM_000463.2(UGT1A1): c.992A> G (p.Gln331Arg) single nucleotide variant Pathogenic rs72551348 GRCh37 Chromosome 2, 234675807: 234675807
2 UGT1A1 NM_000463.2(UGT1A1): c.1456T> G (p.Tyr486Asp) single nucleotide variant Pathogenic rs34993780 GRCh37 Chromosome 2, 234681059: 234681059
3 UGT1A1 UGT1A1, 1-BP DEL, 1223A deletion Pathogenic
4 UGT1A1 NM_000463.2(UGT1A1): c.524T> A (p.Leu175Gln) single nucleotide variant Pathogenic rs72551341 GRCh37 Chromosome 2, 234669457: 234669457
5 UGT1A1 NM_000463.2(UGT1A1): c.1198A> G (p.Asn400Asp) single nucleotide variant Pathogenic rs28934877 GRCh37 Chromosome 2, 234676979: 234676979
6 UGT1A1 NM_000463.2(UGT1A1): c.44T> G (p.Leu15Arg) single nucleotide variant Pathogenic rs111033541 GRCh37 Chromosome 2, 234668977: 234668977

Expression for Crigler-Najjar Syndrome, Type Ii

Search GEO for disease gene expression data for Crigler-Najjar Syndrome, Type Ii.

Pathways for Crigler-Najjar Syndrome, Type Ii

Pathways related to Crigler-Najjar Syndrome, Type Ii according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.87 UGT1A1 UGT1A4 UGT1A6 UGT1A9
2
Show member pathways
12.51 UGT1A1 UGT1A4 UGT1A6 UGT1A9
3 12.28 UGT1A1 UGT1A4 UGT1A6 UGT1A9
4
Show member pathways
12.13 UGT1A1 UGT1A4 UGT1A6 UGT1A9
5 11.9 UGT1A1 UGT1A4 UGT1A6 UGT1A9
6
Show member pathways
11.6 UGT1A1 UGT1A4 UGT1A6 UGT1A9
7
Show member pathways
11.51 UGT1A1 UGT1A9
8
Show member pathways
11.48 UGT1A1 UGT1A4 UGT1A6 UGT1A9
9
Show member pathways
11.47 UGT1A1 UGT1A4 UGT1A9
10
Show member pathways
11.37 UGT1A1 UGT1A4 UGT1A6 UGT1A9
11
Show member pathways
11.3 UGT1A1 UGT1A4 UGT1A6 UGT1A9
12 11.14 UGT1A1 UGT1A4 UGT1A6 UGT1A9
13 10.96 UGT1A4 UGT1A6 UGT1A9
14
Show member pathways
10.88 UGT1A1 UGT1A9
15
Show member pathways
10.79 UGT1A1 UGT1A4 UGT1A6 UGT1A9
16
Show member pathways
10.75 UGT1A4 UGT1A9
17 10.68 UGT1A4 UGT1A9
18 10.43 UGT1A1 UGT1A4 UGT1A6 UGT1A9

GO Terms for Crigler-Najjar Syndrome, Type Ii

Cellular components related to Crigler-Najjar Syndrome, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum GO:0005783 9.46 UGT1A1 UGT1A4 UGT1A6 UGT1A9
2 endoplasmic reticulum membrane GO:0005789 9.26 UGT1A1 UGT1A4 UGT1A6 UGT1A9
3 intracellular membrane-bounded organelle GO:0043231 8.92 UGT1A1 UGT1A4 UGT1A6 UGT1A9

Biological processes related to Crigler-Najjar Syndrome, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metabolic process GO:0008152 9.71 UGT1A1 UGT1A4 UGT1A6 UGT1A9
2 xenobiotic metabolic process GO:0006805 9.46 UGT1A6 UGT1A9
3 cellular glucuronidation GO:0052695 9.46 UGT1A1 UGT1A4 UGT1A6 UGT1A9
4 retinoic acid metabolic process GO:0042573 9.43 UGT1A1 UGT1A9
5 heme catabolic process GO:0042167 9.37 UGT1A1 UGT1A4
6 flavone metabolic process GO:0051552 9.32 UGT1A1 UGT1A9
7 bilirubin conjugation GO:0006789 9.26 UGT1A1 UGT1A4
8 flavonoid glucuronidation GO:0052696 9.26 UGT1A1 UGT1A4 UGT1A6 UGT1A9
9 xenobiotic glucuronidation GO:0052697 8.92 UGT1A1 UGT1A4 UGT1A6 UGT1A9

Molecular functions related to Crigler-Najjar Syndrome, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.71 UGT1A1 UGT1A4 UGT1A6 UGT1A9
2 protein homodimerization activity GO:0042803 9.67 UGT1A1 UGT1A4 UGT1A6 UGT1A9
3 protein heterodimerization activity GO:0046982 9.62 UGT1A1 UGT1A4 UGT1A6 UGT1A9
4 transferase activity, transferring glycosyl groups GO:0016757 9.56 UGT1A1 UGT1A4 UGT1A6 UGT1A9
5 transferase activity, transferring hexosyl groups GO:0016758 9.46 UGT1A1 UGT1A4 UGT1A6 UGT1A9
6 glucuronosyltransferase activity GO:0015020 9.26 UGT1A1 UGT1A4 UGT1A6 UGT1A9
7 retinoic acid binding GO:0001972 8.92 UGT1A1 UGT1A4 UGT1A6 UGT1A9

Sources for Crigler-Najjar Syndrome, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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