MCID: CHL134
MIFTS: 46

Cholestasis, Benign Recurrent Intrahepatic, 1

Categories: Genetic diseases, Rare diseases, Liver diseases, Metabolic diseases, Reproductive diseases, Gastrointestinal diseases, Endocrine diseases

Aliases & Classifications for Cholestasis, Benign Recurrent Intrahepatic, 1

MalaCards integrated aliases for Cholestasis, Benign Recurrent Intrahepatic, 1:

Name: Cholestasis, Benign Recurrent Intrahepatic, 1 57 75
Benign Recurrent Intrahepatic Cholestasis 53 25 59 73
Bric1 57 53 59 75
Cholestasis, Benign Recurrent Intrahepatic 1 53 29 6
Cholestasis, Benign Recurrent Intrahepatic 57 13 55
Summerskill Syndrome 57 53 75
Bric 53 25 59
Low Gamma-Gt Familial Intrahepatic Cholestasis 25 29
Recurrent Familial Intrahepatic Cholestasis 25 75
Summerskill-Walshe-Tygstrup Syndrome 53 59
Cholestasis, Intrahepatic, Recurrent, Benign, Type 1 40
Cholestasis, Progressive Familial Intrahepatic 3 73
Benign Recurrent Intrahepatic Cholestasis Type 1 59
Recurrent Familial Intrahepatic Cholestasis 1 53
Benign Recurrent Intrahepatic Cholestasis 1 53
Abcb11-Related Intrahepatic Cholestasis 25
Atp8b1-Related Intrahepatic Cholestasis 25
Progressive Intrahepatic Cholestasis 73
Mild Atp8b1 Deficiency 53
Bric Type 1 59

Characteristics:

Orphanet epidemiological data:

59
benign recurrent intrahepatic cholestasis
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
allelic disorder to intrahepatic cholestasis of pregnancy (icp, )
disease-free intervals can last weeks to years during which there is no clinical or biochemical evidence of cholestasis
variable age at onset, range from infancy to adulthood
variable frequency and severity
allelic disorder to progressive familial intrahepatic cholestasis-1 (pfic1, )


HPO:

32
cholestasis, benign recurrent intrahepatic, 1:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Cholestasis, Benign Recurrent Intrahepatic, 1

NIH Rare Diseases : 53 Benign recurrent intrahepatic cholestasis (BRIC) is a rare condition that affects the liver. People with this condition experience episodes of cholestasis, during which the liver cells have a reduced ability to release bile (a digestive fluid). Episodes generally begin in the late teens or early twenties and may be accompanied by jaundice, severe itchiness, a vague feeling of discomfort (malaise), irritability, nausea, vomiting, and a lack of appetite. There are two forms of BRIC which are classified based on the genetic cause of the condition. BRIC1 is caused by changes (mutations) in the ATP8B1 gene and BRIC2 is caused by mutations in the ABCB11 gene. Both follow an autosomal recessive pattern of inheritance. Treatment of BRIC may include medications to manage symptoms and specialized therapies (i.e. nasobiliary drainage) to shorten episodes.

MalaCards based summary : Cholestasis, Benign Recurrent Intrahepatic, 1, also known as benign recurrent intrahepatic cholestasis, is related to cholestasis, progressive familial intrahepatic, 1 and cholestasis, and has symptoms including diarrhea, icterus and pruritus. An important gene associated with Cholestasis, Benign Recurrent Intrahepatic, 1 is ATP8B1 (ATPase Phospholipid Transporting 8B1). The drugs Pharmaceutical Solutions and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver and testes, and related phenotypes are nausea and vomiting and hearing impairment

OMIM : 57 Benign recurrent intrahepatic cholestasis is characterized by intermittent episodes of cholestasis without extrahepatic bile duct obstruction. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months (Summerskill and Walshe, 1959; Schapiro and Isselbacher, 1963; Brenard et al., 1989). Tygstrup et al. (1999) stated that referring to this disorder as 'benign' is a misnomer, because the disease has an impact on the quality of life in some patients. They preferred the term 'recurrent familial intrahepatic cholestasis.' (243300)

UniProtKB/Swiss-Prot : 75 Cholestasis, benign recurrent intrahepatic, 1: A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.

Genetics Home Reference : 25 Benign recurrent intrahepatic cholestasis (BRIC) is characterized by episodes of liver dysfunction called cholestasis. During these episodes, the liver cells have a reduced ability to release a digestive fluid called bile. Because the problems with bile release occur within the liver (intrahepatic), the condition is described as intrahepatic cholestasis. Episodes of cholestasis can last from weeks to months, and the time between episodes, during which there are usually no symptoms, can vary from weeks to years.

Related Diseases for Cholestasis, Benign Recurrent Intrahepatic, 1

Graphical network of the top 20 diseases related to Cholestasis, Benign Recurrent Intrahepatic, 1:



Diseases related to Cholestasis, Benign Recurrent Intrahepatic, 1

Symptoms & Phenotypes for Cholestasis, Benign Recurrent Intrahepatic, 1

Symptoms via clinical synopsis from OMIM:

57
Abdomen Liver:
hepatomegaly
intrahepatic cholestasis, episodic, recurrent
jaundice, episodic
progression to end-stage liver disease does not occur

Laboratory Abnormalities:
conjugated hyperbilirubinemia
normal or mildly increased serum gamma-ggt
increased serum bile acids

Abdomen Pancreas:
pancreatitis

Skin Nails Hair Skin:
jaundice, episodic
pruritus, episodic


Clinical features from OMIM:

243300

Human phenotypes related to Cholestasis, Benign Recurrent Intrahepatic, 1:

59 32 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nausea and vomiting 59 32 frequent (33%) Frequent (79-30%) HP:0002017
2 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
3 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
4 abdominal pain 59 32 occasional (7.5%) Occasional (29-5%) HP:0002027
5 pruritus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000989
6 weight loss 59 32 hallmark (90%) Very frequent (99-80%) HP:0001824
7 elevated hepatic transaminases 59 32 hallmark (90%) Very frequent (99-80%) HP:0002910
8 cholestatic liver disease 59 32 hallmark (90%) Very frequent (99-80%) HP:0002611
9 cirrhosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001394
10 cholelithiasis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001081
11 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
12 pancreatitis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001733
13 anorexia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002039
14 chronic diarrhea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002028
15 acholic stools 59 32 hallmark (90%) Very frequent (99-80%) HP:0011985
16 hepatocellular carcinoma 59 32 occasional (7.5%) Occasional (29-5%) HP:0001402
17 hepatomegaly 32 HP:0002240
18 conjugated hyperbilirubinemia 32 HP:0002908
19 intermittent jaundice 32 HP:0001046
20 increased serum bile acid concentration 32 HP:0012202
21 intrahepatic cholestasis with episodic jaundice 32 HP:0006575

UMLS symptoms related to Cholestasis, Benign Recurrent Intrahepatic, 1:


diarrhea, icterus, pruritus

GenomeRNAi Phenotypes related to Cholestasis, Benign Recurrent Intrahepatic, 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.17 ATP8B1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-14 9.17 ABCB11
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.17 ATP8B1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.17 ABCB11 ATP8B1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.17 ATP8B1
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.17 ABCB11

Drugs & Therapeutics for Cholestasis, Benign Recurrent Intrahepatic, 1

Drugs for Cholestasis, Benign Recurrent Intrahepatic, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 3
2 Liver Extracts Phase 2
3 Bile Acids and Salts Phase 2
4 Anticholesteremic Agents Phase 1
5 Antimetabolites Phase 1
6 Cholestyramine Resin Phase 1
7 Hypolipidemic Agents Phase 1
8 Lipid Regulating Agents Phase 1
9 Cola Nutraceutical Phase 1
10
Pancrelipase Approved, Investigational 53608-75-6
11
Iron Approved 7439-89-6 23925
12
Glycerol Approved, Investigational 56-81-5 753
13 Estrogens
14 Alpha 1-Antitrypsin
15 pancreatin
16 Protein C Inhibitor
17 Gastrointestinal Agents
18
Bilirubin 635-65-4 5280352
19 Hematinics
20 4-phenylbutyric acid
21 Protective Agents

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 This Study Will Investigate the Efficacy and Safety of A4250 in Children With PFIC 1 or 2 Recruiting NCT03566238 Phase 3 A4250;Placebo
2 Efficacy and Safety of Maralixibat (SHP625) in the Treatment of Participants With Progressive Familial Intrahepatic Cholestasis (PFIC) Not yet recruiting NCT03353454 Phase 3 Maralixibat;Placebo
3 Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis Active, not recruiting NCT02057718 Phase 2 LUM001
4 An Open Label, Single-dose, Single Period ADME Study of A4250 in Healthy Subjects Completed NCT03082937 Phase 1 3 mg [14C]-A4250 capsule
5 A Safety and Pharmakokinetic Study of A4250 Alone or in Combination With A3384 Completed NCT02963077 Phase 1 A4250;CRC (A3384);Questran;Placebo
6 Validation of the Itch Reported Outcome (ItchRO) Diaries in Pediatric Cholestatic Liver Disease Completed NCT02131623
7 ABCB4 Gene Mutations in Intrahepatic Cholestasis of Pregnancy and Controls Completed NCT00700232
8 Shear Wave Sonoelastography in Pediatric Liver Fibrosis Completed NCT02372682
9 Evaluating the Genetic Causes and Progression of Cholestatic Liver Diseases (LOGIC) Recruiting NCT00571272
10 Sulfation of Bile Acids as a Biomarker for Hepatobiliary Diseases Recruiting NCT01200082
11 China Registry for Genetic / Metabolic Liver Diseases Recruiting NCT03131427 Standard of care
12 Buphenyl Therapy for Byler's Disease No longer available NCT01784718 Buphenyl
13 Transition From Buphenyl to RAVICTI for the Therapy of Byler Disease No longer available NCT01949766 Glycerol phenylbutyrate
14 Expanded Access Protocol for an Intermediate Size Population - RAVICTI for Byler Disease Temporarily not available NCT02094222 RAVICTI

Search NIH Clinical Center for Cholestasis, Benign Recurrent Intrahepatic, 1

Genetic Tests for Cholestasis, Benign Recurrent Intrahepatic, 1

Genetic tests related to Cholestasis, Benign Recurrent Intrahepatic, 1:

# Genetic test Affiliating Genes
1 Cholestasis, Benign Recurrent Intrahepatic 1 29 ATP8B1
2 Low Gamma-Gt Familial Intrahepatic Cholestasis 29

Anatomical Context for Cholestasis, Benign Recurrent Intrahepatic, 1

MalaCards organs/tissues related to Cholestasis, Benign Recurrent Intrahepatic, 1:

41
Liver, Testes

Publications for Cholestasis, Benign Recurrent Intrahepatic, 1

Articles related to Cholestasis, Benign Recurrent Intrahepatic, 1:

(show top 50) (show all 71)
# Title Authors Year
1
Benign recurrent intrahepatic cholestasis (BRIC)-like episode associated with ATP8B1 variation underlying protracted cholestatic course of acute hepatitis E virus infection. ( 29191380 )
2018
2
Can genetic testing guide the therapy of cholestatic pruritus? A case of benign recurrent intrahepatic cholestasis type 2 with severe nasobiliary drainage-refractory itch. ( 29404523 )
2018
3
Benign Recurrent Intrahepatic Cholestasis in a Young Adult. ( 27504332 )
2016
4
Compound heterozygous mutations of ABCB11 responsible for benign recurrent intrahepatic cholestasis. ( 25565657 )
2015
5
Endoscopic nasobiliary drainage improves jaundice attack symptoms in benign recurrent intrahepatic cholestasis: A case report. ( 23403701 )
2013
6
Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis. ( 24164717 )
2013
7
Clinical signs and genetic sequencing of benign recurrent intrahepatic cholestasis. ( 24342334 )
2013
8
Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis: a review. ( 23402083 )
2012
9
A case report: nasobiliary drainage inducing remission in benign recurrent intrahepatic cholestasis. ( 22505385 )
2012
10
Benign recurrent intrahepatic cholestasis: review and long-term follow-up of five cases. ( 22229830 )
2012
11
Description of two new ABCB11 mutations responsible for type 2 benign recurrent intrahepatic cholestasis in a French-Canadian family. ( 21766090 )
2011
12
Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. ( 20955958 )
2010
13
Mutation specific drug therapy for progressive familial or benign recurrent intrahepatic cholestasis: a new tool in a near future? ( 20537422 )
2010
14
Benign recurrent intrahepatic cholestasis: late initial diagnosis in adulthood. ( 20526019 )
2010
15
Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1. ( 19731236 )
2009
16
Successful treatment with colestimide for a bout of cholestasis in a Japanese patient with benign recurrent intrahepatic cholestasis caused by ATP8B1 mutation. ( 18379143 )
2008
17
Benign recurrent intrahepatic cholestasis (BRIC) in an adult. ( 18416353 )
2007
18
Depletion of high-density lipoprotein and appearance of triglyceride-rich low-density lipoprotein in a Japanese patient with FIC1 deficiency manifesting benign recurrent intrahepatic cholestasis. ( 17592371 )
2007
19
Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump. ( 16394881 )
2006
20
Nasobiliary drainage induces long-lasting remission in benign recurrent intrahepatic cholestasis. ( 16374853 )
2006
21
Modified laparoscopic external biliary diversion for benign recurrent intrahepatic cholestasis in obese adolescents. ( 16736228 )
2006
22
Benign recurrent intrahepatic cholestasis. ( 16186684 )
2005
23
Benign recurrent intrahepatic cholestasis with secondary renal impairment treated with extracorporeal albumin dialysis. ( 15827452 )
2005
24
Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. ( 15300568 )
2004
25
Benign recurrent intrahepatic cholestasis. ( 15062197 )
2004
26
Indel in the FIC1/ATP8B1 gene-a novel rare type of mutation associated with benign recurrent intrahepatic cholestasis. ( 15341767 )
2004
27
Extracorporal albumin dialysis (MARS) improves cholestasis and normalizes low apo A-I levels in a patient with benign recurrent intrahepatic cholestasis (BRIC). ( 12220310 )
2002
28
Benign recurrent intrahepatic cholestasis progressing to progressive familial intrahepatic cholestasis: low GGT cholestasis is a clinical continuum. ( 11867191 )
2002
29
Successful clinical application of extracorporal albumin dialysis in a patient with benign recurrent intrahepatic cholestasis (BRIC). ( 16215886 )
2001
30
Autosomal dominant benign recurrent intrahepatic cholestasis (BRIC) unlinked to 18q21 and 2q24. ( 11146465 )
2000
31
Benign recurrent intrahepatic cholestasis in a Saudi child. ( 10690264 )
1999
32
Benign recurrent intrahepatic cholestasis. ( 11291237 )
1999
33
Benign recurrent intrahepatic cholestasis. ( 9170826 )
1997
34
Benign recurrent intrahepatic cholestasis (BRIC): evidence of genetic heterogeneity and delimitation of the BRIC locus to a 7-cM interval between D18S69 and D18S64. ( 9272159 )
1997
35
Benign recurrent intrahepatic cholestasis: improvement of pruritus and shortening of the symptomatic phase with rifampin therapy: a case report. ( 9272324 )
1997
36
Intractable cough and abnormal pulmonary function in benign recurrent intrahepatic cholestasis. ( 8855752 )
1996
37
Benign recurrent intrahepatic cholestasis and Byler's disease: one gene, two diseases? ( 8895021 )
1996
38
Benign recurrent intrahepatic cholestasis. Some reflections on a case followed for 20 years. ( 8539477 )
1995
39
Mapping of a locus for progressive familial intrahepatic cholestasis (Byler disease) to 18q21-q22, the benign recurrent intrahepatic cholestasis region. ( 7655458 )
1995
40
Autosomal-recessive inheritance of benign recurrent intrahepatic cholestasis. ( 7677155 )
1995
41
Benign recurrent intrahepatic cholestasis. ( 8772982 )
1995
42
Benign recurrent intrahepatic cholestasis: a long-term follow-up. ( 7959556 )
1994
43
Genome screening by searching for shared segments: mapping a gene for benign recurrent intrahepatic cholestasis. ( 7894490 )
1994
44
Efficacy of ursodeoxycholic acid in preventing cholestatic episodes in a patient with benign recurrent intrahepatic cholestasis. ( 1639361 )
1992
45
Failure of ursodeoxycholic acid to prevent a cholestatic episode in a patient with benign recurrent intrahepatic cholestasis: a study of bile acid metabolism. ( 2050325 )
1991
46
Benign recurrent intrahepatic cholestasis. A clinico-pathologic study. ( 2356403 )
1990
47
Benign recurrent intrahepatic cholestasis: failure of S-adenosylmethionine therapy. ( 2391074 )
1990
48
Benign recurrent intrahepatic cholestasis: a long-term follow-up study of two patients. ( 2925156 )
1989
49
Benign recurrent intrahepatic cholestasis. A report of 26 cases. ( 2794432 )
1989
50
Benign recurrent intrahepatic cholestasis: treatment with S-adenosylmethionine. ( 2703120 )
1989

Variations for Cholestasis, Benign Recurrent Intrahepatic, 1

UniProtKB/Swiss-Prot genetic disease variations for Cholestasis, Benign Recurrent Intrahepatic, 1:

75
# Symbol AA change Variation ID SNP ID
1 ATP8B1 p.Ile661Thr VAR_008812 rs121909100
2 ATP8B1 p.Gly892Arg VAR_008813 rs121909098
3 ATP8B1 p.Gly308Asp VAR_043049
4 ATP8B1 p.Ile344Phe VAR_043050 rs140665115
5 ATP8B1 p.Ser453Tyr VAR_043056
6 ATP8B1 p.Asp454Gly VAR_043057
7 ATP8B1 p.Arg600Gln VAR_043063
8 ATP8B1 p.Arg600Trp VAR_043064
9 ATP8B1 p.Arg628Trp VAR_043065 rs752045131
10 ATP8B1 p.Ile694Thr VAR_043068 rs541474497

ClinVar genetic disease variations for Cholestasis, Benign Recurrent Intrahepatic, 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 ATP8B1 NM_005603.4(ATP8B1): c.1982T> C (p.Ile661Thr) single nucleotide variant Pathogenic rs121909100 GRCh37 Chromosome 18, 55336665: 55336665
2 ATP8B1 NM_005603.4(ATP8B1): c.1982T> C (p.Ile661Thr) single nucleotide variant Pathogenic rs121909100 GRCh38 Chromosome 18, 57669433: 57669433
3 ATP8B1 ATP8B1, 9-BP DEL, NT2384 deletion Pathogenic
4 ATP8B1 ATP8B1, IVS23AS, C-A, -3 single nucleotide variant Pathogenic
5 ATP8B1 NM_005603.5(ATP8B1): c.2286-2A> G single nucleotide variant Pathogenic rs377132123 GRCh37 Chromosome 18, 55329849: 55329849
6 ATP8B1 NM_005603.5(ATP8B1): c.2286-2A> G single nucleotide variant Pathogenic rs377132123 GRCh38 Chromosome 18, 57662617: 57662617
7 ATP8B1 NM_005603.5(ATP8B1): c.1799G> A (p.Arg600Gln) single nucleotide variant Pathogenic GRCh37 Chromosome 18, 55342086: 55342086
8 ATP8B1 NM_005603.5(ATP8B1): c.1799G> A (p.Arg600Gln) single nucleotide variant Pathogenic GRCh38 Chromosome 18, 57674854: 57674854

Expression for Cholestasis, Benign Recurrent Intrahepatic, 1

Search GEO for disease gene expression data for Cholestasis, Benign Recurrent Intrahepatic, 1.

Pathways for Cholestasis, Benign Recurrent Intrahepatic, 1

GO Terms for Cholestasis, Benign Recurrent Intrahepatic, 1

Biological processes related to Cholestasis, Benign Recurrent Intrahepatic, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 bile acid and bile salt transport GO:0015721 8.62 ABCB11 ATP8B1

Sources for Cholestasis, Benign Recurrent Intrahepatic, 1

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