Congenital bile acid synthesis defect type 2

General Information (adopted from Orphanet):

Synonyms, Signs: CHOLESTASIS WITH DELTA(4)-3-OXOSTEROID 5-BETA-REDUCTASE DEFICIENCY
CBAS2
Cholestasis, with delta(4)-3-oxosteroid 5-beta-reductase deficiency
Number of Symptoms 31
OrphanetNr: 79303
OMIM Id: 235555
ICD-10: K76.8
UMLs: C1856127
MeSH: C535443
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Bile acid synthesis defect with cholestasis and malabsorption
 -Rare genetic disease
 -Rare hepatic disease

Symptom Information: Sort by abundance 

1
 (HPO:0004349) Reduced bone mineral density Occasional [Orphanet] 165 / 7739
2
 (HPO:0100626) Chronic hepatic failure Frequent [Orphanet] 7 / 7739
3
 (HPO:0000952) Jaundice 105 / 7739
4
 (HPO:0001406) Intrahepatic cholestasis 16 / 7739
5
 (HPO:0001744) Splenomegaly Very frequent [Orphanet] 337 / 7739
6
 (HPO:0002570) Steatorrhea 31 / 7739
7
 (HPO:0001410) Decreased liver function Very frequent [Orphanet] 59 / 7739
8
 (HPO:0001399) Hepatic failure 80 / 7739
9
 (HPO:0002014) Diarrhea 225 / 7739
10
 (HPO:0001394) Cirrhosis Frequent [Orphanet] 102 / 7739
11
 (HPO:0001396) Cholestasis Very frequent [Orphanet] 136 / 7739
12
 (HPO:0002024) Malabsorption Very frequent [Orphanet] 142 / 7739
13
 (HPO:0002910) Elevated hepatic transaminases Very frequent [Orphanet] 158 / 7739
14
 (HPO:0002240) Hepatomegaly Very frequent [Orphanet] 467 / 7739
15
 (HPO:0001508) Failure to thrive 454 / 7739
16
 (HPO:0003256) Abnormality of the coagulation cascade 19 / 7739
17
 (HPO:0003010) Prolonged bleeding time Frequent [Orphanet] 88 / 7739
18
 (HPO:0003155) Elevated alkaline phosphatase 52 / 7739
19
 (HPO:0002904) Hyperbilirubinemia 32 / 7739
20
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
21
 (OMIM) Septal fibrosis 2 / 7739
22
 (OMIM) Malabsorption of fat and fat-soluble vitamins 7 / 7739
23
 (OMIM) Coagulopathy secondary to liver disease 4 / 7739
24
 (HPO:0001522) Death in infancy Occasional [Orphanet] 275 / 7739
25
 (OMIM) Decreased or absent serum and urinary chenodeoxycholic acid and cholic acid 1 / 7739
26
 (OMIM) Hepatocyte necrosis 1 / 7739
27
 (HPO:0003623) Neonatal onset 22 / 7739
28
 (OMIM) Giant cell transformation on biopsy 1 / 7739
29
 (OMIM) Liver failure before adulthood 1 / 7739
30
 (OMIM) Normal serum levels of gamma-GGT (231950) 2 / 7739
31
 (OMIM) Canalicular cholestasis 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Setchell et al. (1988) reported monozygotic male twins who presented at birth with cholestatic jaundice due to severe intrahepatic cholestasis. A previously born sib had died at the age of 4 months of hepatic failure following an identical ...
Genotype-Phenotype Correlations OMIM Drury et al. (2010) noted that a patient with a homozygous truncating mutation in the ARK1D1 gene (604741.0002; Lemonde et al., 2003) had a more severe phenotype necessitating liver transplantation compared to 2 sibs with compound heterozygous missense ...
Molecular genetics OMIM In an infant with clinical and biochemical features of 5-beta-reductase deficiency, including urinary bile salts with a 3-oxo-delta(4) content greater than 94%, Sumazaki et al. (1997) excluded a pathogenic mutation in the AKR1D1 gene.

In 3 ...