CBAS1
MCID: BLC007
MIFTS: 45

Bile Acid Synthesis Defect, Congenital, 1 (CBAS1)

Categories: Gastrointestinal diseases, Genetic diseases, Liver diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Oral diseases, Rare 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 58 30 13 6 45 74
Cbas1 58 12 54 26 76
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 58 54 60 76
Congenital Bile Acid Synthesis Defect Type 1 54 26 60
Congenital Bile Acid Synthesis Defect 1 12 76 15
Basd1 54 60
3-Alpha Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase, Deficiency of 54
3beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 26
3beta-Hydroxy-Delta-5-C27-Steroid Dehydrogenase Deficiency 26
Progressive Familial Intrahepatic Cholestasis Type 4 76
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase 13
Cholestasis, Progressive Familial Intrahepatic 4 74
Bile Acid Synthesis Defect, Congenital, Type 1 41
Congenital Bile Acid Synthesis Defect, Type 1 54
Neonatal Progressive Intrahepatic Cholestasis 76
3beta-Hsdh Deficiency 26
Pfic4 76

Characteristics:

Orphanet epidemiological data:

60
congenital bile acid synthesis defect type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

58
Inheritance:
autosomal recessive

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


HPO:

33
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 : 54 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.

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 diarrhea and icterus. 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), and among its related pathways/superpathways are Neuroscience and Dopamine-DARPP32 Feedback onto cAMP Pathway. Affiliated tissues include liver and testes, and related phenotypes are failure to thrive and hepatomegaly

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 : 26 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 : 58 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 : 76 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

Graphical network of the top 20 diseases related to Bile Acid Synthesis Defect, Congenital, 1:



Diseases related to Bile Acid Synthesis Defect, Congenital, 1

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

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

60 33 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 60 33 hallmark (90%) Very frequent (99-80%) HP:0001508
2 hepatomegaly 60 33 hallmark (90%) Very frequent (99-80%) HP:0002240
3 malabsorption 60 33 hallmark (90%) Very frequent (99-80%) HP:0002024
4 elevated hepatic transaminase 60 33 hallmark (90%) Very frequent (99-80%) HP:0002910
5 jaundice 60 33 hallmark (90%) Very frequent (99-80%) HP:0000952
6 biliary tract abnormality 60 33 hallmark (90%) Very frequent (99-80%) HP:0001080
7 neonatal cholestatic liver disease 60 33 hallmark (90%) Very frequent (99-80%) HP:0006566
8 splenomegaly 60 33 frequent (33%) Frequent (79-30%) HP:0001744
9 gastrointestinal hemorrhage 60 33 frequent (33%) Frequent (79-30%) HP:0002239
10 abnormality of coagulation 60 33 frequent (33%) Frequent (79-30%) HP:0001928
11 osteoporosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0000939
12 pruritus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000989
13 peripheral neuropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0009830
14 cirrhosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0001394
15 nyctalopia 60 33 occasional (7.5%) Occasional (29-5%) HP:0000662
16 abnormal bleeding 60 Occasional (29-5%)
17 hepatic failure 33 HP:0001399
18 diarrhea 33 HP:0002014
19 hyperbilirubinemia 33 HP:0002904
20 acholic stools 33 HP:0011985
21 abnormality of the coagulation cascade 33 HP:0003256
22 intrahepatic cholestasis 33 HP:0001406
23 steatorrhea 33 HP:0002570
24 hypocholesterolemia 33 HP:0003146
25 giant cell hepatitis 33 HP:0200084

Symptoms via clinical synopsis from OMIM:

58
Growth Other:
failure to thrive

Abdomen External Features:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
progressive liver failure
more
Skin Nails Hair Skin:
jaundice

Laboratory Abnormalities:
abnormal liver function tests
decreased serum cholesterol
increased serum bilirubin
normal serum levels of gamma-ggt

Abdomen Spleen:
splenomegaly

Skeletal:
rickets

Abdomen Gastrointestinal:
diarrhea
steatorrhea
malabsorption of fat and fat-soluble vitamins
discolored, acholic stools

Hematology:
coagulopathy secondary to liver disease

Clinical features from OMIM:

607765

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


diarrhea, icterus

GenomeRNAi Phenotypes related to Bile Acid Synthesis Defect, Congenital, 1 according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased caspase 3/7 activity GR00318-A 8.62 GRIN2A GRIN2B

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

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Acute Gastrointestinal Tolerability Following a Single Serving of a Novel Dietary Fiber Completed NCT02530762 Not Applicable
2 Gastrointestinal Tolerability Following Multiple Servings of a Novel Dietary Fiber Completed NCT02532985 Not Applicable

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 30 HSD3B7

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 1

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

42
Liver, Testes

Publications for Bile Acid Synthesis Defect, Congenital, 1

Articles related to Bile Acid Synthesis Defect, Congenital, 1:

# Title Authors Year
1
Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease. ( 12679481 )
2003
2
The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis. ( 11067870 )
2000
3
[3 beta-hydroxy-delta 5-C27-steroid-oxidoreductase/isomerase deficiency]. ( 9645061 )
1998
4
Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids. ( 3470305 )
1987

Variations for Bile Acid Synthesis Defect, Congenital, 1

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

76
# 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
# Gene Variation Type Significance SNP ID Assembly Location
1 HSD3B7 NM_025193.3(HSD3B7): c.1039_1040delCT (p.Leu347Valfs) deletion Pathogenic rs397514442 GRCh37 Chromosome 16, 30999433: 30999434
2 HSD3B7 NM_025193.3(HSD3B7): c.1039_1040delCT (p.Leu347Valfs) deletion Pathogenic rs397514442 GRCh38 Chromosome 16, 30988112: 30988113
3 HSD3B7 NM_025193.3(HSD3B7): c.294dup (p.Lys99Glnfs) duplication Pathogenic rs397514443 GRCh37 Chromosome 16, 30997497: 30997497
4 HSD3B7 NM_025193.3(HSD3B7): c.294dup (p.Lys99Glnfs) duplication Pathogenic rs397514443 GRCh38 Chromosome 16, 30986176: 30986176
5 HSD3B7 NM_025193.3(HSD3B7): c.322+1G> T single nucleotide variant Pathogenic rs387906288 GRCh37 Chromosome 16, 30997526: 30997526
6 HSD3B7 NM_025193.3(HSD3B7): c.322+1G> T single nucleotide variant Pathogenic rs387906288 GRCh38 Chromosome 16, 30986205: 30986205
7 HSD3B7 NM_025193.3(HSD3B7): c.439G> A (p.Glu147Lys) single nucleotide variant Pathogenic rs104894518 GRCh37 Chromosome 16, 30997933: 30997933
8 HSD3B7 NM_025193.3(HSD3B7): c.439G> A (p.Glu147Lys) single nucleotide variant Pathogenic rs104894518 GRCh38 Chromosome 16, 30986612: 30986612
9 HSD3B7 NM_025193.3(HSD3B7): c.45_46delAG (p.Gly17Leufs) deletion Pathogenic rs786200876 GRCh37 Chromosome 16, 30997024: 30997025
10 HSD3B7 NM_025193.3(HSD3B7): c.45_46delAG (p.Gly17Leufs) deletion Pathogenic rs786200876 GRCh38 Chromosome 16, 30985703: 30985704

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

Pathways related to Bile Acid Synthesis Defect, Congenital, 1 according to GeneCards Suite gene sharing:

(show all 14)
# Super pathways Score Top Affiliating Genes
1 12.07 GRIN2A GRIN2B
2 11.88 GRIN2A GRIN2B
3 11.84 GRIN2A GRIN2B
4
Show member pathways
11.76 GRIN2A GRIN2B
5
Show member pathways
11.7 GRIN2A GRIN2B
6
Show member pathways
11.57 GRIN2A GRIN2B
7
Show member pathways
11.5 GRIN2A GRIN2B
8
Show member pathways
11.46 GRIN2A GRIN2B
9
Show member pathways
11.33 GRIN2A GRIN2B
10 11.19 GRIN2A GRIN2B
11 10.86 GRIN2A GRIN2B
12 10.62 GRIN2A GRIN2B
13 10.42 GRIN2A GRIN2B
14 9.95 GRIN2A GRIN2B

GO Terms for Bile Acid Synthesis Defect, Congenital, 1

Cellular components related to Bile Acid Synthesis Defect, Congenital, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynaptic density GO:0014069 9.32 GRIN2A GRIN2B
2 postsynaptic membrane GO:0045211 9.26 GRIN2A GRIN2B
3 synaptic membrane GO:0097060 9.16 GRIN2A GRIN2B
4 postsynaptic density membrane GO:0098839 8.96 GRIN2A GRIN2B
5 NMDA selective glutamate receptor complex GO:0017146 8.62 GRIN2A GRIN2B

Biological processes related to Bile Acid Synthesis Defect, Congenital, 1 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.52 GRIN2A GRIN2B
2 brain development GO:0007420 9.51 GRIN2A GRIN2B
3 response to ethanol GO:0045471 9.48 GRIN2A GRIN2B
4 calcium-mediated signaling GO:0019722 9.46 GRIN2A GRIN2B
5 excitatory postsynaptic potential GO:0060079 9.43 GRIN2A GRIN2B
6 learning or memory GO:0007611 9.4 GRIN2A GRIN2B
7 regulation of synaptic plasticity GO:0048167 9.37 GRIN2A GRIN2B
8 long-term synaptic potentiation GO:0060291 9.32 GRIN2A GRIN2B
9 ionotropic glutamate receptor signaling pathway GO:0035235 9.26 GRIN2A GRIN2B
10 MAPK cascade GO:0000165 9.19 GRIN2B
11 glutamate receptor signaling pathway GO:0007215 9.16 GRIN2A GRIN2B
12 excitatory chemical synaptic transmission GO:0098976 8.96 GRIN2A GRIN2B
13 calcium ion transmembrane import into cytosol GO:0097553 8.62 GRIN2A GRIN2B

Molecular functions related to Bile Acid Synthesis Defect, Congenital, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor activity GO:0038023 9.32 GRIN2A GRIN2B
2 ion channel activity GO:0005216 9.26 GRIN2A GRIN2B
3 ionotropic glutamate receptor activity GO:0004970 9.16 GRIN2A GRIN2B
4 NMDA glutamate receptor activity GO:0004972 8.96 GRIN2A GRIN2B
5 glutamate-gated calcium ion channel activity GO:0022849 8.62 GRIN2A GRIN2B

Sources for Bile Acid Synthesis Defect, Congenital, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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