CBAS1
MCID: BLC007
MIFTS: 45

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 56 13 43 71
Congenital Bile Acid Synthesis Defect 1 12 73 29 6 15
Cbas1 56 12 52 25 73
3-Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 56 52 58 73
Congenital Bile Acid Synthesis Defect Type 1 52 25 58
Basd1 52 58
3-Alpha Beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase, Deficiency of 52
3beta-Hydroxy-Delta-5-C27-Steroid Oxidoreductase Deficiency 25
3beta-Hydroxy-Delta-5-C27-Steroid Dehydrogenase Deficiency 25
Progressive Familial Intrahepatic Cholestasis Type 4 73
Cholestasis, Progressive Familial Intrahepatic 4 71
Bile Acid Synthesis Defect, Congenital, Type 1 39
Congenital Bile Acid Synthesis Defect, Type 1 52
Neonatal Progressive Intrahepatic Cholestasis 73
3beta-Hsdh Deficiency 25
Pfic4 73

Characteristics:

Orphanet epidemiological data:

58
congenital bile acid synthesis defect type 1
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

56
Miscellaneous:
neonatal onset
favorable response to oral bile acid therapy
caused by inborn error in bile acid synthesis

Inheritance:
autosomal recessive


HPO:

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


Classifications:

Orphanet: 58  
Rare hepatic diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0111071
OMIM 56 607765
OMIM Phenotypic Series 56 PS607765
MESH via Orphanet 44 C535442
ICD10 via Orphanet 33 K76.8
UMLS via Orphanet 72 C1843116
Orphanet 58 ORPHA79301
MedGen 41 C1843116
UMLS 71 C1843116 C2931067

Summaries for Bile Acid Synthesis Defect, Congenital, 1

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 79301 Definition Congenital 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. Epidemiology Prevalence is unknown but may be around 1-9/1,000,000 for overall BAS defects, excluding cerebrotendinous xanthomatosis. Clinical description The 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. Etiology The 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 methods Diagnosis 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 diagnosis Differential 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 diagnosis Antenatal 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 treatment Treatment 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. Prognosis With 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 congenital bile acid synthesis defect 1, is related to cholestasis and cholestasis, progressive familial intrahepatic, 4, 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 Reelin signaling pathway and nNOS Signaling at Neuronal Synapses. Affiliated tissues include liver, testes and eye, and related phenotypes are hepatomegaly and malabsorption

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 : 56 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 : 73 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 in the Disorder of Bile Acid Synthesis family:

Bile Acid Synthesis Defect, Congenital, 4 Bile Acid Synthesis Defect, Congenital, 2
Bile Acid Synthesis Defect, Congenital, 1 Bile Acid Synthesis Defect, Congenital, 3
Bile Acid Synthesis Defect, Congenital, 5 Bile Acid Synthesis Defect, Congenital, 6
Congenital Bile Acid Synthesis Defect

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

(show top 50) (show all 140)
# Related Disease Score Top Affiliating Genes
1 cholestasis 29.7 SLC25A13 HSD3B7 GGT1 ALB
2 cholestasis, progressive familial intrahepatic, 4 11.7
3 congenital bile acid synthesis defect 11.7
4 epilepsy, focal, with speech disorder and with or without mental retardation 10.4 GRIN2B GRIN2A
5 bile acid synthesis defect, congenital, 2 10.3 HSD3B7 HSD3B1
6 landau-kleffner syndrome 10.3 GRIN2B GRIN2A
7 ocular dominance 10.3 GRIN2B GRIN2A
8 heart aneurysm 10.2 SCRN3 ALB
9 coronary aneurysm 10.2 SCRN3 ALB
10 lingual-facial-buccal dyskinesia 10.2 GRIN2B GRIN2A
11 ascending cholangitis 10.2 GGTLC3 ALB
12 hepatocellular carcinoma 10.1
13 autosomal recessive disease 10.1
14 progressive familial intrahepatic cholestasis 10.1
15 intrahepatic cholestasis of pregnancy 10.1
16 portal hypertension 10.1
17 liver cirrhosis 10.1
18 familial intrahepatic cholestasis 10.1
19 hepatic tuberculosis 10.1 GGT1 ALB
20 mediastinitis 10.0 TTR ALB
21 intracranial embolism 10.0 TTR ALB
22 marasmus 10.0 TTR ALB
23 kwashiorkor 10.0 TTR ALB
24 toxic encephalopathy 10.0 GRIN2B GRIN2A ALB
25 analbuminemia 10.0 TTR ALB
26 kagami-ogata syndrome 10.0 GRIN2B GRIN2A ALB
27 congenital intrinsic factor deficiency 10.0 SMAD9 ALB
28 specific developmental disorder 10.0 GRIN2B GRIN2A ALB
29 bile duct rhabdomyosarcoma 10.0 GGTLC3 GGT2 GGT1
30 splenic tuberculosis 9.9 GGTLC3 GGT2 GGT1
31 perforation of bile duct 9.9 GGTLC3 GGT2 GGT1
32 gallbladder papillary carcinoma 9.9 GGTLC3 GGT2 GGT1
33 immature teratoma of ovary 9.9 GGTLC3 GGT2 GGT1
34 optic nerve astrocytoma 9.9 GGTLC3 GGT2 GGT1
35 myasthenic syndrome, congenital, 3b, fast-channel 9.9 GGTLC3 GGT2 GGT1
36 suppurative cholangitis 9.9 GGTLC3 GGT2 GGT1
37 dientamoebiasis 9.9 GGTLC3 GGT2 GGT1
38 algoneurodystrophy 9.9 GGTLC3 GGT2 GGT1
39 bile duct cysts 9.9 GGTLC3 GGT2 GGT1
40 glutathionuria 9.9 GGTLC3 GGT2 GGT1
41 noonan syndrome 8 9.9 GGTLC3 GGT2 GGT1
42 amelogenesis imperfecta, type if 9.9 GGTLC3 GGT2 GGT1
43 familial adenomatous polyposis 2 9.9 GGTLC3 GGT2 GGT1
44 giant axonal neuropathy 1, autosomal recessive 9.9 GGTLC3 GGT2 GGT1
45 cataract 34, multiple types 9.9 GGTLC3 GGT2 GGT1
46 loeys-dietz syndrome 2 9.9 GGTLC3 GGT2 GGT1
47 loeys-dietz syndrome 9.9 GGTLC3 GGT2 GGT1
48 cataract 4, multiple types 9.9 GGTLC3 GGT2 GGT1
49 contractural arachnodactyly, congenital 9.9 GGTLC3 GGT2 GGT1
50 cholestasis, progressive familial intrahepatic, 1 9.9 GGTLC3 GGT2 GGT1

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:

58 31 (show all 26)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
2 malabsorption 58 31 hallmark (90%) Very frequent (99-80%) HP:0002024
3 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
4 elevated hepatic transaminase 58 31 hallmark (90%) Very frequent (99-80%) HP:0002910
5 jaundice 58 31 hallmark (90%) Very frequent (99-80%) HP:0000952
6 biliary tract abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0001080
7 neonatal cholestatic liver disease 58 31 hallmark (90%) Very frequent (99-80%) HP:0006566
8 splenomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0001744
9 gastrointestinal hemorrhage 58 31 frequent (33%) Frequent (79-30%) HP:0002239
10 abnormality of coagulation 58 31 frequent (33%) Frequent (79-30%) HP:0001928
11 peripheral neuropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0009830
12 pruritus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000989
13 cirrhosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001394
14 osteoporosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000939
15 nyctalopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000662
16 rickets 31 HP:0002748
17 hepatic failure 31 HP:0001399
18 abnormal bleeding 58 Occasional (29-5%)
19 steatorrhea 31 HP:0002570
20 hyperbilirubinemia 31 HP:0002904
21 hypocholesterolemia 31 HP:0003146
22 acholic stools 31 HP:0011985
23 diarrhea 31 HP:0002014
24 intrahepatic cholestasis 31 HP:0001406
25 abnormality of the coagulation cascade 31 HP:0003256
26 giant cell hepatitis 31 HP:0200084

Symptoms via clinical synopsis from OMIM:

56
Abdomen Spleen:
splenomegaly

Growth Other:
failure to thrive

Skin Nails Hair Skin:
jaundice

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

Abdomen External Features:
hepatomegaly
cirrhosis
jaundice
intrahepatic cholestasis
progressive liver failure
more
Skeletal:
rickets

Abdomen Gastrointestinal:
steatorrhea
diarrhea
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

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 Congenital Bile Acid Synthesis Defect 1 29 HSD3B7

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 1

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

40
Liver, Testes, Eye, Bone, Spleen, Skin

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. 56 6
12679481 2003
2
The bile acid synthetic gene 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase is mutated in progressive intrahepatic cholestasis. 56 6
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. 56 6
3470305 1987
4
A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency. 56
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. 56
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. 56
1979336 1990
7
A new syndrome of bile acid deficiency-a possible synthetic defect. 56
4795443 1973
8
New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report. 61
32089630 2020
9
[Progressive familial intrahepatic cholestasis related to mutation of the TJP2 gene: recent advances]. 61
26983395 2016

Variations for Bile Acid Synthesis Defect, Congenital, 1

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HSD3B7 NM_025193.4(HSD3B7):c.1039_1040del (p.Leu347fs)deletion Pathogenic 2881 rs397514442 16:30999433-30999434 16:30988112-30988113
2 HSD3B7 NM_025193.4(HSD3B7):c.294dup (p.Lys99fs)duplication Pathogenic 2882 rs397514443 16:30997494-30997495 16:30986173-30986174
3 HSD3B7 NM_025193.4(HSD3B7):c.322+1G>TSNV Pathogenic 2883 rs387906288 16:30997526-30997526 16:30986205-30986205
4 HSD3B7 NM_025193.4(HSD3B7):c.439G>A (p.Glu147Lys)SNV Pathogenic 2884 rs104894518 16:30997933-30997933 16:30986612-30986612
5 HSD3B7 NM_025193.4(HSD3B7):c.45_46del (p.Gly17fs)deletion Pathogenic 2885 rs786200876 16:30997024-30997025 16:30985703-30985704

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

73
# 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:

# Super pathways Score Top Affiliating Genes
1 10.83 GRIN2B GRIN2A
2 10.78 GRIN2B GRIN2A
3 10.65 GRIN2B GRIN2A
4 10.54 GGT2 GGT1
5 10.32 GGT2 GGT1
6 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 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:

# Name GO ID Score Top Affiliating Genes
1 ionotropic glutamate receptor signaling pathway GO:0035235 9.46 GRIN2B GRIN2A
2 zymogen activation GO:0031638 9.43 GGT2 GGT1
3 glutamate receptor signaling pathway GO:0007215 9.4 GRIN2B GRIN2A
4 excitatory chemical synaptic transmission GO:0098976 9.37 GRIN2B GRIN2A
5 regulation of immune system process GO:0002682 9.32 GGT2 GGT1
6 calcium ion transmembrane import into cytosol GO:0097553 9.26 GRIN2B GRIN2A
7 peptide modification GO:0031179 9.16 GGT2 GGT1
8 glutathione catabolic process GO:0006751 9.13 GGTLC3 GGT2 GGT1
9 leukotriene D4 biosynthetic process GO:1901750 8.8 GGTLC3 GGT2 GGT1

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

# Name GO ID Score Top Affiliating Genes
1 glutamate receptor activity GO:0008066 9.4 GRIN2B GRIN2A
2 ionotropic glutamate receptor activity GO:0004970 9.37 GRIN2B GRIN2A
3 NMDA glutamate receptor activity GO:0004972 9.32 GRIN2B GRIN2A
4 3-beta-hydroxy-delta5-steroid dehydrogenase activity GO:0003854 9.26 HSD3B7 HSD3B1
5 glutamate-gated calcium ion channel activity GO:0022849 9.16 GRIN2B GRIN2A
6 peptidyltransferase activity GO:0000048 8.96 GGT2 GGT1
7 glutathione hydrolase activity GO:0036374 8.8 GGTLC3 GGT2 GGT1

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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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