MCID: BLC007
MIFTS: 34

Bile Acid Synthesis Defect, Congenital, 1

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

Aliases & Classifications for Bile Acid Synthesis Defect, Congenital, 1

MalaCards integrated aliases for Bile Acid Synthesis Defect, Congenital, 1:

Name: Bile Acid Synthesis Defect, Congenital, 1 53 28 13 41 69
Cbas1 53 12 49 24 71
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 53 49 55 71
Congenital Bile Acid Synthesis Defect Type 1 49 24 55
Congenital Bile Acid Synthesis Defect 1 12 71
Basd1 49 55
3-Alpha Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase, Deficiency of 49
3beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 24
3beta-Hydroxy-Delta-5-C27-Steroid Dehydrogenase Deficiency 24
Progressive Familial Intrahepatic Cholestasis Type 4 71
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase 13
Cholestasis, Progressive Familial Intrahepatic 4 69
Congenital Bile Acid Synthesis Defect, Type 1 49
Neonatal Progressive Intrahepatic Cholestasis 71
3beta-Hsdh Deficiency 24
Pfic4 71

Characteristics:

Orphanet epidemiological data:

55
congenital bile acid synthesis defect type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
neonatal onset
favorable response to oral bile acid therapy
caused by inborn error in bile acid synthesis


HPO:

31
bile acid synthesis defect, congenital, 1:
Onset and clinical course neonatal onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Bile Acid Synthesis Defect, Congenital, 1

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79301Disease definitionCongenital bile acid synthesis defect type 1 (BAS defect type 1) is the most common anomaly of bile acid synthesis (see this term) characterized by variable manifestations of progressive cholestatic liver disease, and fat malabsorption.EpidemiologyPrevalence is unknown but may be around 1-9/1,000,000 for overall BAS defects, excluding cerebrotendinous xanthomatosis.Clinical descriptionThe clinical presentation is heterogeneous, however most patients present with features of neonatal cholestasis. Clinical features include hepatomegaly with or without splenomegaly, jaundice, fat and fat-soluble vitamin malabsorption, and mild steatorrhea. In most cases, pruritus is absent. Liver function tests present elevated serum transaminases (AST, ALT), conjugated hyperbilirubinemia, and normal gamma-GT. The liver histology shows inflammation, giant cells, evidence of cholestasis, and variable degrees of liver fibrosis. The clinical course of early-onset disease is heterogeneous with some patients resolving jaundice and being identified later in life, or with more fulminant disease that results in death or requires liver transplantation at an early age. The disorder may also present as late-onset chronic cholestasis. In such patients, liver disease is not always evident and patients may have fat-soluble vitamin malabsorption with rickets, corrected by vitamin supplementation, and/or other complications including bleeding diathesis (hematochezia or intracranial bleeding), neuroaxonal dystrophy and night blindness. Serum liver enzymes are initially often normal but later show increases with progression of liver disease to fibrosis. Children and adolescents may also present with extensive fibrosis and/or cirrhosis.EtiologyThe disease is caused by a mutation in the gene encoding 3-beta-hydroxy-delta-5-C27 steroid oxidoreductase (HSD3B7, 16p12-p11.2). Transmission is autosomal recessive.Diagnostic methodsDiagnosis is based on detection of sulfate and glycosulfate conjugates of 3-beta-hydroxy-delta-5 bile acids, which are the signature metabolites of this bile acid defect, on liquid secondary ionization mass spectrometry (LSIMS) analysis of urine. Gas chromatography - mass spectrometry (GC-MS) or electroscopy and tandem mass spectrometry may also be used.Differential diagnosisDifferential diagnoses include progressive familial intrahepatic cholestasis, diseases that present with neonatal cholestasis, which includes alpha-1-antitrypsin deficiency of ZZ phenotype, Alagille syndrome, biliary atresia, cystic fibrosis, and metabolic diseases (tyrosinemia type I, galactosemia, hereditary fructose intolerance) (see these terms), diseases that present with fat and fat soluble vitamin malabsorption, including other liver diseases, and intestinal disease, or diseases that present with growth failure.Antenatal diagnosisAntenatal diagnosis can be made on embryonic tissue obtained when there has been a previously identified sibling. Urine LSIMS in a suspect infant can confirm the diagnosis in the first neonatal days.Management and treatmentTreatment is based on oral administration of cholic acid which leads to gradual resolution of biochemical and histologic abnormalities and prevents progression of the disease, even in cases with hepatic fibrosis and cirrhosis. Cholic acid therapy stimulates bile flow and suppresses synthesis of atypical bile acids and production of toxic intermediates via the bile acid pathway linked to the pathogenesis of disease.PrognosisWith early treatment the long-term prognosis is excellent.Visit the Orphanet disease page for more resources. Last updated: 1/1/2011

MalaCards based summary : Bile Acid Synthesis Defect, Congenital, 1, also known as cbas1, is related to cholestasis, progressive familial intrahepatic, 4 and congenital bile acid synthesis defect, and has symptoms including pruritus, failure to thrive and splenomegaly. An important gene associated with Bile Acid Synthesis Defect, Congenital, 1 is HSD3B7 (Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- And Steroid Delta-Isomerase 7). The drugs Doxorubicin and Doxil have been mentioned in the context of this disorder. Affiliated tissues include liver and testes.

Disease Ontology : 12 A congenital bile acid synthesis defect characterized by progressive cholestatic liver disease, giant cell hepatitis, malabsorption of fat and fat-soluble vitamins, increased serum bilirubin and decreased serum cholesterol that has material basis in homozygous or compound heterozygous mutation in the HSD3B7 gene on chromosome 16p.

Genetics Home Reference : 24 Congenital bile acid synthesis defect type 1 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 1 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.

OMIM : 53 Congenital defects of bile acid synthesis are autosomal recessive disorders characterized by neonatal onset of progressive liver disease with cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract resulting from a primary failure to synthesize bile acids. Affected infants show failure to thrive and secondary coagulopathy. In most forms of the disorder, there is a favorable response to oral bile acid therapy (summary by Cheng et al., 2003). (607765)

UniProtKB/Swiss-Prot : 71 Congenital bile acid synthesis defect 1: A primary defect in bile synthesis leading to progressive liver disease. Clinical features include neonatal jaundice, severe intrahepatic cholestasis, cirrhosis.

Related Diseases for Bile Acid Synthesis Defect, Congenital, 1

Diseases related to Bile Acid Synthesis Defect, Congenital, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cholestasis, progressive familial intrahepatic, 4 11.3
2 congenital bile acid synthesis defect 11.3
3 intrahepatic cholestasis 9.5 HSD3B7 TJP2
4 cholestasis 9.4 HSD3B7 TJP2

Symptoms & Phenotypes for Bile Acid Synthesis Defect, Congenital, 1

Symptoms via clinical synopsis from OMIM:

53
Abdomen Gastroin testinal:
diarrhea
steatorrhea
malabsorption of fat and fat-soluble vitamins
discolored, acholic stools

Abdomen Spleen:
splenomegaly

Skin Nails Hair Skin:
jaundice

Hematology:
coagulopathy secondary to liver disease

Growth Other:
failure to thrive

Abdomen External Features:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
progressive liver failure
more
Laboratory Abnormalities:
abnormal liver function tests
decreased serum cholesterol
increased serum bilirubin
normal serum levels of gamma-ggt


Clinical features from OMIM:

607765

Human phenotypes related to Bile Acid Synthesis Defect, Congenital, 1:

55 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pruritus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000989
2 failure to thrive 55 31 hallmark (90%) Very frequent (99-80%) HP:0001508
3 splenomegaly 55 31 frequent (33%) Frequent (79-30%) HP:0001744
4 hepatomegaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0002240
5 malabsorption 55 31 hallmark (90%) Very frequent (99-80%) HP:0002024
6 osteoporosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000939
7 peripheral neuropathy 55 31 occasional (7.5%) Occasional (29-5%) HP:0009830
8 elevated hepatic transaminases 55 31 hallmark (90%) Very frequent (99-80%) HP:0002910
9 cirrhosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001394
10 jaundice 55 31 hallmark (90%) Very frequent (99-80%) HP:0000952
11 nyctalopia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000662
12 biliary tract abnormality 55 31 hallmark (90%) Very frequent (99-80%) HP:0001080
13 gastrointestinal hemorrhage 55 31 frequent (33%) Frequent (79-30%) HP:0002239
14 abnormality of coagulation 55 31 frequent (33%) Frequent (79-30%) HP:0001928
15 neonatal cholestatic liver disease 55 31 hallmark (90%) Very frequent (99-80%) HP:0006566
16 diarrhea 31 HP:0002014
17 abnormal bleeding 55 Occasional (29-5%)
18 hepatic failure 31 HP:0001399
19 hyperbilirubinemia 31 HP:0002904
20 acholic stools 31 HP:0011985
21 intrahepatic cholestasis 31 HP:0001406
22 steatorrhea 31 HP:0002570
23 hypocholesterolemia 31 HP:0003146
24 abnormality of the coagulation cascade 31 HP:0003256
25 giant cell hepatitis 31 HP:0200084

UMLS symptoms related to Bile Acid Synthesis Defect, Congenital, 1:


icterus, diarrhea

Drugs & Therapeutics for Bile Acid Synthesis Defect, Congenital, 1

Drugs for Bile Acid Synthesis Defect, Congenital, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Doxorubicin Approved, Investigational Phase 1 23214-92-8 31703
2
Doxil Approved June 1999 Phase 1 31703
3 Topoisomerase Inhibitors Phase 1
4 Anti-Bacterial Agents Phase 1
5 Antibiotics, Antitubercular Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin Not yet recruiting NCT03002805 Phase 1 CBT-1®
2 Acute Gastrointestinal Tolerability Following a Single Serving of a Novel Dietary Fiber Completed NCT02530762
3 Gastrointestinal Tolerability Following Multiple Servings of a Novel Dietary Fiber Completed NCT02532985

Search NIH Clinical Center for Bile Acid Synthesis Defect, Congenital, 1

Cochrane evidence based reviews: bile acid synthesis defect, congenital, 1

Genetic Tests for Bile Acid Synthesis Defect, Congenital, 1

Genetic tests related to Bile Acid Synthesis Defect, Congenital, 1:

# Genetic test Affiliating Genes
1 Bile Acid Synthesis Defect, Congenital, 1 28 HSD3B7

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 1

MalaCards organs/tissues related to Bile Acid Synthesis Defect, Congenital, 1:

38
Liver, Testes

Publications for Bile Acid Synthesis Defect, Congenital, 1

Variations for Bile Acid Synthesis Defect, Congenital, 1

UniProtKB/Swiss-Prot genetic disease variations for Bile Acid Synthesis Defect, Congenital, 1:

71
# Symbol AA change Variation ID SNP ID
1 HSD3B7 p.Gly19Ser VAR_054775
2 HSD3B7 p.Glu147Lys VAR_054776 rs104894518

ClinVar genetic disease variations for Bile Acid Synthesis Defect, Congenital, 1:

6 (show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 TJP2 NM_004817.3(TJP2): c.766_769delGCCT (p.Ala256Thrfs) deletion Pathogenic rs587777518 GRCh37 Chromosome 9, 71836226: 71836229
2 TJP2 NM_004817.3(TJP2): c.885delC (p.Ser296Alafs) deletion Pathogenic rs587777519 GRCh37 Chromosome 9, 71836345: 71836345
3 TJP2 NM_004817.3(TJP2): c.1361delC (p.Ala454Glyfs) deletion Pathogenic rs587777520 GRCh37 Chromosome 9, 71842938: 71842938
4 TJP2 NM_004817.3(TJP2): c.1992-2A> G single nucleotide variant Pathogenic rs587777521 GRCh37 Chromosome 9, 71851863: 71851863
5 HSD3B7 NM_025193.3(HSD3B7): c.1039_1040delCT (p.Leu347Valfs) deletion Pathogenic rs397514442 GRCh37 Chromosome 16, 30999433: 30999434
6 HSD3B7 NM_025193.3(HSD3B7): c.294dupC (p.Lys99Glnfs) duplication Pathogenic rs397514443 GRCh37 Chromosome 16, 30997497: 30997497
7 HSD3B7 NM_025193.3(HSD3B7): c.322+1G> T single nucleotide variant Pathogenic rs387906288 GRCh37 Chromosome 16, 30997526: 30997526
8 HSD3B7 NM_025193.3(HSD3B7): c.439G> A (p.Glu147Lys) single nucleotide variant Pathogenic rs104894518 GRCh37 Chromosome 16, 30997933: 30997933
9 HSD3B7 NM_025193.3(HSD3B7): c.45_46delAG (p.Gly17Leufs) deletion Pathogenic rs786200876 GRCh37 Chromosome 16, 30997024: 30997025
10 TJP2 NM_004817.3(TJP2): c.3408_3573del166 (p.Ser1136Argfs) deletion Pathogenic GRCh37 Chromosome 9, 71869125: 71869290
11 TJP2 NM_004817.3(TJP2): c.2668-1G> T single nucleotide variant Pathogenic rs864321695 GRCh37 Chromosome 9, 71862927: 71862927
12 TJP2 NM_004817.3(TJP2): c.2438dupT (p.Asn814Glnfs) duplication Pathogenic rs864321696 GRCh37 Chromosome 9, 71854935: 71854935
13 TJP2 NM_004817.3(TJP2): c.817delG (p.Ala273Profs) deletion Pathogenic rs864321697 GRCh37 Chromosome 9, 71836277: 71836277
14 TJP2 NM_004817.3(TJP2): c.1697T> A (p.Leu566Ter) single nucleotide variant Pathogenic rs886042381 GRCh37 Chromosome 9, 71849380: 71849380
15 HSD3B7 NM_025193.3(HSD3B7): c.890delT (p.Phe297Serfs) deletion Pathogenic rs886043511 GRCh37 Chromosome 16, 30999284: 30999284
16 TJP2 NM_004817.3(TJP2): c.498dupG (p.Arg167Alafs) duplication Pathogenic rs886044313 GRCh37 Chromosome 9, 71835958: 71835958
17 TJP2 NM_004817.3(TJP2): c.1243delT (p.Ser415Leufs) deletion Pathogenic rs1057518679 GRCh38 Chromosome 9, 69227797: 69227797
18 TJP2 NG_016342.1: g.(102053_104579)_(123841_130382)dup duplication Pathogenic GRCh38 Chromosome 9, 69218360: 69246689
19 TJP2 NM_004817.3(TJP2): c.813_814delCG (p.Ala273Profs) deletion Pathogenic GRCh38 Chromosome 9, 69221357: 69221358

Expression for Bile Acid Synthesis Defect, Congenital, 1

Search GEO for disease gene expression data for Bile Acid Synthesis Defect, Congenital, 1.

Pathways for Bile Acid Synthesis Defect, Congenital, 1

GO Terms for Bile Acid Synthesis Defect, Congenital, 1

Sources for Bile Acid Synthesis Defect, Congenital, 1

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
Content
Loading form....