CBAS1
MCID: BLC007
MIFTS: 43

Bile Acid Synthesis Defect, Congenital, 1 (CBAS1)

Categories: Blood diseases, 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 57 29 13 6 44 72
Cbas1 57 12 53 25 74
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 57 53 59 74
Congenital Bile Acid Synthesis Defect Type 1 53 25 59
Congenital Bile Acid Synthesis Defect 1 12 74 15
Basd1 53 59
3-Alpha Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase, Deficiency of 53
3beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 25
3beta-Hydroxy-Delta-5-C27-Steroid Dehydrogenase Deficiency 25
Progressive Familial Intrahepatic Cholestasis Type 4 74
Cholestasis, Progressive Familial Intrahepatic 4 72
Bile Acid Synthesis Defect, Congenital, Type 1 40
Congenital Bile Acid Synthesis Defect, Type 1 53
Neonatal Progressive Intrahepatic Cholestasis 74
3beta-Hsdh Deficiency 25
Pfic4 74

Characteristics:

Orphanet epidemiological data:

59
congenital bile acid synthesis defect type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

57
Miscellaneous:
neonatal onset
favorable response to oral bile acid therapy
caused by inborn error in bile acid synthesis

Inheritance:
autosomal recessive


HPO:

32
bile acid synthesis defect, congenital, 1:
Inheritance autosomal recessive inheritance
Onset and clinical course neonatal onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0111071
MESH via Orphanet 45 C535442
ICD10 via Orphanet 34 K76.8
UMLS via Orphanet 73 C1843116
Orphanet 59 ORPHA79301
MedGen 42 C1843116
UMLS 72 C1843116 C2931067

Summaries for Bile Acid Synthesis Defect, Congenital, 1

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79301DefinitionCongenital 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 Cytokine Signaling in Immune system and Dopamine-DARPP32 Feedback onto cAMP Pathway. Affiliated tissues include liver, testes and skin, 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 : 25 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. The signs and symptoms of congenital bile acid synthesis defect type 1 often develop during the first weeks of life, but they can begin anytime from infancy into adulthood. Affected infants often have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile. Excess fat in the feces (steatorrhea) is an additional feature of congenital bile acid synthesis defect type 1. As the condition progresses, affected individuals can develop liver abnormalities including an enlarged liver (hepatomegaly), inflammation, or chronic liver disease (cirrhosis). The spleen may also become enlarged (splenomegaly). The inability to absorb certain fat-soluble vitamins (vitamin D in particular) can result in softening and weakening of the bones (rickets) in some individuals. If left untreated, congenital bile acid synthesis defect type 1 often leads to cirrhosis and death in childhood.

OMIM : 57 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 : 74 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:

59 32 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
2 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
3 malabsorption 59 32 hallmark (90%) Very frequent (99-80%) HP:0002024
4 elevated hepatic transaminase 59 32 hallmark (90%) Very frequent (99-80%) HP:0002910
5 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
6 biliary tract abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0001080
7 neonatal cholestatic liver disease 59 32 hallmark (90%) Very frequent (99-80%) HP:0006566
8 splenomegaly 59 32 frequent (33%) Frequent (79-30%) HP:0001744
9 gastrointestinal hemorrhage 59 32 frequent (33%) Frequent (79-30%) HP:0002239
10 abnormality of coagulation 59 32 frequent (33%) Frequent (79-30%) HP:0001928
11 osteoporosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000939
12 pruritus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000989
13 peripheral neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0009830
14 cirrhosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001394
15 nyctalopia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000662
16 rickets 32 HP:0002748
17 abnormal bleeding 59 Occasional (29-5%)
18 hepatic failure 32 HP:0001399
19 diarrhea 32 HP:0002014
20 hyperbilirubinemia 32 HP:0002904
21 acholic stools 32 HP:0011985
22 abnormality of the coagulation cascade 32 HP:0003256
23 intrahepatic cholestasis 32 HP:0001406
24 steatorrhea 32 HP:0002570
25 hypocholesterolemia 32 HP:0003146
26 giant cell hepatitis 32 HP:0200084

Symptoms via clinical synopsis from OMIM:

57
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:

26
# 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

Search Clinical Trials , 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 29 HSD3B7

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 1

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

41
Liver, Testes, Skin, Bone, Spleen, Eye

Publications for Bile Acid Synthesis Defect, Congenital, 1

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

# Title Authors PMID Year
1
Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease. 8 71
12679481 2003
2
The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis. 8 71
11067870 2000
3
Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy-and 3 beta,7 alpha, 12 alpha-trihydroxy-5-cholenoic acids. 8 71
3470305 1987
4
A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency. 8
7915305 1994
5
Bile acids and bile alcohols in a child with hepatic 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency: effects of chenodeoxycholic acid treatment. 8
2072042 1991
6
Lack of 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase in fibroblasts from a child with urinary excretion of 3 beta-hydroxy-delta 5-bile acids. A new inborn error of metabolism. 8
1979336 1990
7
A new syndrome of bile acid deficiency-a possible synthetic defect. 8
4795443 1973
8
[Progressive familial intrahepatic cholestasis related to mutation of the TJP2 gene: recent advances]. 38
26983395 2016

Variations for Bile Acid Synthesis Defect, Congenital, 1

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 HSD3B7 NM_025193.4(HSD3B7): c.1039_1040del (p.Leu347fs) deletion Pathogenic rs397514442 16:30999433-30999434 16:30988112-30988113
2 HSD3B7 NM_025193.4(HSD3B7): c.294dup (p.Lys99fs) duplication Pathogenic rs397514443 16:30997497-30997497 16:30986176-30986176
3 HSD3B7 NM_025193.4(HSD3B7): c.322+1G> T single nucleotide variant Pathogenic rs387906288 16:30997526-30997526 16:30986205-30986205
4 HSD3B7 NM_025193.4(HSD3B7): c.439G> A (p.Glu147Lys) single nucleotide variant Pathogenic rs104894518 16:30997933-30997933 16:30986612-30986612
5 HSD3B7 NM_025193.4(HSD3B7): c.45_46del (p.Gly17fs) deletion Pathogenic rs786200876 16:30997024-30997025 16:30985703-30985704

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

74
# Symbol AA change Variation ID SNP ID
1 HSD3B7 p.Gly19Ser VAR_054775
2 HSD3B7 p.Glu147Lys VAR_054776 rs104894518

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
Show member pathways
12.82 GRIN2B GRIN2A CD40LG
2 11.88 GRIN2B GRIN2A
3 11.84 GRIN2B GRIN2A
4
Show member pathways
11.76 GRIN2B GRIN2A
5
Show member pathways
11.7 GRIN2B GRIN2A
6
Show member pathways
11.57 GRIN2B GRIN2A
7
Show member pathways
11.5 GRIN2B GRIN2A
8
Show member pathways
11.46 GRIN2B GRIN2A
9
Show member pathways
11.33 GRIN2B GRIN2A
10 11.19 GRIN2B GRIN2A
11 10.86 GRIN2B GRIN2A
12 10.62 GRIN2B GRIN2A
13 10.42 GRIN2B GRIN2A
14 9.95 GRIN2B GRIN2A

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 cell surface GO:0009986 9.43 GRIN2B GRIN2A CD40LG
2 synaptic membrane GO:0097060 9.16 GRIN2B GRIN2A
3 postsynaptic density membrane GO:0098839 8.96 GRIN2B GRIN2A
4 NMDA selective glutamate receptor complex GO:0017146 8.62 GRIN2B GRIN2A

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

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

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

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

Sources for Bile Acid Synthesis Defect, Congenital, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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