CBAS2
MCID: BLC008
MIFTS: 27

Bile Acid Synthesis Defect, Congenital, 2 (CBAS2)

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, 2

MalaCards integrated aliases for Bile Acid Synthesis Defect, Congenital, 2:

Name: Bile Acid Synthesis Defect, Congenital, 2 57 29 13 13 6 44 73
Cholestasis with Delta(4)-3-Oxosteroid 5-Beta-Reductase Deficiency 57 12 53 25 59 75
Cbas2 57 12 53 25 75
Congenital Bile Acid Synthesis Defect 2 12 75 15
Congenital Bile Acid Synthesis Defect Type 2 25 59
Bile Acid Synthesis Defect, Congenital, Type 2 40
Congenital Bile Acid Synthesis Defect, Type 2 53
Basd2 59

Characteristics:

Orphanet epidemiological data:

59
congenital bile acid synthesis defect type 2
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: infantile;

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
bile acid synthesis defect, congenital, 2:
Onset and clinical course neonatal onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 235555
Disease Ontology 12 DOID:0111069
Orphanet 59 ORPHA79303
MESH via Orphanet 45 C535443
UMLS via Orphanet 74 C1856127
ICD10 via Orphanet 34 K76.8
MedGen 42 C1856127
UMLS 73 C1856127

Summaries for Bile Acid Synthesis Defect, Congenital, 2

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 79303Disease definitionCongenital bile acid synthesis defect type 2 (BAS defect type 2) is an anomaly of bile acid synthesis (see this term) characterized by severe and rapidly progressive cholestatic liver disease, and malabsorption of fat and fat-soluble vitamins.EpidemiologyPrevalence is unknown. This condition is clearly rare but is the second most common anomaly of BAS on screening infants with cholestasis.Clinical descriptionPatients present with neonatal cholestasis and rapid progression to cirrhosis and death in infancy without intervention. The clinical presentation resembles that of congenital BAS defect type 1 (see this term) with hepatosplenomegaly, jaundice, fat-soluble vitamin malabsorption, and steatorrhea. However, the average age at diagnosis is lower, in infancy, and disease progression is more rapid and severe. Liver function tests present elevated serum transaminases (AST, ALT) and gamma-GT, markedly elevated conjugated bilirubinemia and coagulopathy.EtiologyBAS defect type 2 is caused by a mutation in the delta(4)-3-oxosteroid 5-beta-reductase gene (AKR1D1, 7q32-q33). Transmission is autosomal recessive. Liver injury is thought to be caused by diminished primary bile acid synthesis and hepatotoxicity of accumulated atypical bile acids (delta(4)-3-oxo bile acids).Diagnostic methodsDiagnosis is based on urine analysis using liquid secondary ionization mass spectrometry (LSIMS) and gas chromatography - mass spectrometry (GC-MS). LSIMS urine analysis reveals elevated amounts of delta(4)-3-oxo bile acids including 3-oxo-7alpha-hydroxy-4-cholenoic and 3-oxo-7alpha, 12alpha-dihydroxy-4-cholenoic acids. Increased production of delta4-3-oxo bile acids occurs in infants during the first few weeks of life and in patients with end-stage liver disease of other causes. It is important to perform repeat LSIMS urine analysis as, on rare occasions, a resolution of the liver disease occurs with disappearance of atypical bile acids.Differential diagnosisDifferential diagnoses include progressive familial intrahepatic cholestasis, diseases that present with neonatal cholestasis, which includes alpha-1-antitrypsin deficiency (ZZ phenotype), tyrosinemia type 1, biliary atresia, choledochal cyst, cystic fibrosis, Alagille syndrome, galactosemia and hereditary fructose intolerance or diseases that present with growth failure (panhypopituitarism) (see these terms).Antenatal diagnosisAntenatal diagnosis can be established by analysis of embryonic tissue when there has been a previously identified sibling. Urine LSIMS on siblings of affected patients may be performed in the first neonatal days and therapy begun before serious morbidity develops.Management and treatmentTreatment is based on oral bile acid therapy, which leads to gradual resolution of biochemical and histologic abnormalities and prevents progression of the disease. Cholic acid therapy creates a pool of bile acids which stimulates bile flow and facilitates fat soluble vitamin absorption and suppresses atypical bile acid synthesis thereby reducing the production of toxic bile acid metabolic intermediates. Ursodeoxycholic acid (UDCA) may be used but is not the therapy of choice because UDCA does not suppress atypical bile acid synthesis and the toxic metabolites that may injure the liver continue to be produced.PrognosisWith early treatment, the long-term prognosis is excellent. If a patient is identified with advanced liver disease, cholic acid therapy may not be effective and liver transplantation may be required. Without treatment, the condition is generally fatal.Visit the Orphanet disease page for more resources.

MalaCards based summary : Bile Acid Synthesis Defect, Congenital, 2, also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency, is related to congenital bile acid synthesis defect, and has symptoms including diarrhea and icterus. An important gene associated with Bile Acid Synthesis Defect, Congenital, 2 is AKR1D1 (Aldo-Keto Reductase Family 1 Member D1). The drugs Medroxyprogesterone acetate and Antineoplastic Agents, Hormonal have been mentioned in the context of this disorder. Affiliated tissues include liver and testes, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A congenital bile acid synthesis defect characterized by rapid progession of severe cholestatic liver disease, decreased levels of chenodeoxycholic acid and cholic acid in the serum and urine, and malabsorption of fat and fat-soluble vitamins that has material basis in homozygous or compound heterozygous mutation in the AKR1D1 gene on chromosome 7q33.

Genetics Home Reference : 25 Congenital bile acid synthesis defect type 2 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 2 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.

UniProtKB/Swiss-Prot : 75 Congenital bile acid synthesis defect 2: A condition characterized by jaundice, intrahepatic cholestasis and hepatic failure. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.

Description from OMIM: 235555

Related Diseases for Bile Acid Synthesis Defect, Congenital, 2

Diseases in the Congenital Bile Acid Synthesis Defect 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

Diseases related to Bile Acid Synthesis Defect, Congenital, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 congenital bile acid synthesis defect 10.1

Symptoms & Phenotypes for Bile Acid Synthesis Defect, Congenital, 2

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Abdomen Liver:
hepatomegaly
jaundice
intrahepatic cholestasis
giant cell transformation on biopsy
canalicular cholestasis
more
Abdomen Gastrointestinal:
diarrhea
steatorrhea
malabsorption of fat and fat-soluble vitamins

Hematology:
coagulopathy secondary to liver disease

Abdomen Spleen:
splenomegaly

Skin Nails Hair Skin:
jaundice

Laboratory Abnormalities:
hyperbilirubinemia
increased serum alkaline phosphatase
abnormal liver function tests
normal serum levels of gamma-ggt
decreased or absent serum and urinary chenodeoxycholic acid and cholic acid


Clinical features from OMIM:

235555

Human phenotypes related to Bile Acid Synthesis Defect, Congenital, 2:

59 32 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 splenomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001744
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 osteoporosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000939
5 abnormal bleeding 59 32 frequent (33%) Frequent (79-30%) HP:0001892
6 cirrhosis 59 32 frequent (33%) Frequent (79-30%) HP:0001394
7 jaundice 59 32 hallmark (90%) Very frequent (99-80%) HP:0000952
8 biliary tract abnormality 59 32 hallmark (90%) Very frequent (99-80%) HP:0001080
9 neonatal cholestatic liver disease 59 32 hallmark (90%) Very frequent (99-80%) HP:0006566
10 chronic hepatic failure 59 32 frequent (33%) Frequent (79-30%) HP:0100626
11 failure to thrive 32 HP:0001508
12 elevated hepatic transaminases 59 Very frequent (99-80%)
13 diarrhea 32 HP:0002014
14 hepatic failure 32 HP:0001399
15 hyperbilirubinemia 32 HP:0002904
16 abnormality of the coagulation cascade 32 HP:0003256
17 intrahepatic cholestasis 32 HP:0001406
18 elevated alkaline phosphatase 32 HP:0003155
19 steatorrhea 32 HP:0002570
20 elevated hepatic transaminase 32 hallmark (90%) HP:0002910

UMLS symptoms related to Bile Acid Synthesis Defect, Congenital, 2:


diarrhea, icterus

Drugs & Therapeutics for Bile Acid Synthesis Defect, Congenital, 2

Drugs for Bile Acid Synthesis Defect, Congenital, 2 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Medroxyprogesterone acetate Approved, Investigational Early Phase 1 71-58-9
2 Antineoplastic Agents, Hormonal Early Phase 1
3 Contraceptive Agents Early Phase 1
4
Medroxyprogesterone Early Phase 1 520-85-4 10631
5 Contraceptives, Oral Early Phase 1
6 Contraceptive Agents, Male Early Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Clinical Study of Depo Provera Comparing Lay Health Workers and Clinically-trained Health Workers Recruiting NCT03255941 Early Phase 1 DMPA;Sayana Press

Search NIH Clinical Center for Bile Acid Synthesis Defect, Congenital, 2

Cochrane evidence based reviews: bile acid synthesis defect, congenital, 2

Genetic Tests for Bile Acid Synthesis Defect, Congenital, 2

Genetic tests related to Bile Acid Synthesis Defect, Congenital, 2:

# Genetic test Affiliating Genes
1 Bile Acid Synthesis Defect, Congenital, 2 29 AKR1D1

Anatomical Context for Bile Acid Synthesis Defect, Congenital, 2

MalaCards organs/tissues related to Bile Acid Synthesis Defect, Congenital, 2:

41
Liver, Testes

Publications for Bile Acid Synthesis Defect, Congenital, 2

Articles related to Bile Acid Synthesis Defect, Congenital, 2:

# Title Authors Year
1
[Clinical feature and genetic analysis of a family affected by congenital bile acid synthesis defect type 2: identification of 2 novel mutations in AKR1D1 gene]. ( 28697823 )
2017

Variations for Bile Acid Synthesis Defect, Congenital, 2

UniProtKB/Swiss-Prot genetic disease variations for Bile Acid Synthesis Defect, Congenital, 2:

75
# Symbol AA change Variation ID SNP ID
1 AKR1D1 p.Leu106Phe VAR_033007 rs121918343
2 AKR1D1 p.Pro198Leu VAR_033008 rs121918342
3 AKR1D1 p.Pro133Arg VAR_044430 rs267606649
4 AKR1D1 p.Arg261Cys VAR_044431 rs267606650

ClinVar genetic disease variations for Bile Acid Synthesis Defect, Congenital, 2:

6 (show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 AKR1D1 NM_005989.3(AKR1D1): c.593C> T (p.Pro198Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs121918342 GRCh37 Chromosome 7, 137791367: 137791367
2 AKR1D1 NM_005989.3(AKR1D1): c.593C> T (p.Pro198Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs121918342 GRCh38 Chromosome 7, 138106621: 138106621
3 AKR1D1 AKR1D1, 1-BP DEL, 511T deletion Pathogenic
4 AKR1D1 NM_005989.3(AKR1D1): c.316C> T (p.Leu106Phe) single nucleotide variant Pathogenic rs121918343 GRCh37 Chromosome 7, 137776568: 137776568
5 AKR1D1 NM_005989.3(AKR1D1): c.316C> T (p.Leu106Phe) single nucleotide variant Pathogenic rs121918343 GRCh38 Chromosome 7, 138091822: 138091822
6 AKR1D1 NM_005989.3(AKR1D1): c.398C> G (p.Pro133Arg) single nucleotide variant Pathogenic rs267606649 GRCh37 Chromosome 7, 137782631: 137782631
7 AKR1D1 NM_005989.3(AKR1D1): c.398C> G (p.Pro133Arg) single nucleotide variant Pathogenic rs267606649 GRCh38 Chromosome 7, 138097885: 138097885
8 AKR1D1 NM_005989.3(AKR1D1): c.781C> T (p.Arg261Cys) single nucleotide variant Pathogenic rs267606650 GRCh37 Chromosome 7, 137792252: 137792252
9 AKR1D1 NM_005989.3(AKR1D1): c.781C> T (p.Arg261Cys) single nucleotide variant Pathogenic rs267606650 GRCh38 Chromosome 7, 138107506: 138107506
10 AKR1D1 NM_005989.3(AKR1D1): c.261+1G> T single nucleotide variant Likely pathogenic rs201988060 GRCh37 Chromosome 7, 137773515: 137773515
11 AKR1D1 NM_005989.3(AKR1D1): c.261+1G> T single nucleotide variant Likely pathogenic rs201988060 GRCh38 Chromosome 7, 138088769: 138088769
12 AKR1D1 NM_005989.3(AKR1D1): c.93+1G> T single nucleotide variant Likely pathogenic rs916587979 GRCh38 Chromosome 7, 138076612: 138076612
13 AKR1D1 NM_005989.3(AKR1D1): c.93+1G> T single nucleotide variant Likely pathogenic rs916587979 GRCh37 Chromosome 7, 137761358: 137761358
14 AKR1D1 NM_005989.3(AKR1D1): c.580-1G> A single nucleotide variant Likely pathogenic rs749744865 GRCh38 Chromosome 7, 138106607: 138106607
15 AKR1D1 NM_005989.3(AKR1D1): c.580-1G> A single nucleotide variant Likely pathogenic rs749744865 GRCh37 Chromosome 7, 137791353: 137791353

Expression for Bile Acid Synthesis Defect, Congenital, 2

Search GEO for disease gene expression data for Bile Acid Synthesis Defect, Congenital, 2.

Pathways for Bile Acid Synthesis Defect, Congenital, 2

GO Terms for Bile Acid Synthesis Defect, Congenital, 2

Sources for Bile Acid Synthesis Defect, Congenital, 2

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69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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