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Congenital bile acid synthesis defect type 3
Congenital bile acid synthesis defect type 3 (BAS defect type 3) is a severe anomaly of bile acid synthesis (see this term) characterized by severe neonatal cholestatic liver disease.
ORPHA:79302Classification level: Disorder
- Oxysterol 7-alpha-hydroxylase deficiency
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Neonatal, Infancy
- ICD-10: K76.8
- OMIM: 613812
- UMLS: C3151147
- MeSH: C566340
- GARD: -
- MedDRA: -
To date, only 2 cases of this disorder have been reported.
The index case was a 10-week-old infant with severe progressive cholestasis, hepatosplenomegaly, coagulopathy, cirrhosis and liver synthetic failure from early infancy. Serum transaminases (AST, ALT) were markedly elevated and gamma-GT was normal. Liver histology showed cholestasis, extensive portal fibrosis, inflammation and giant cell transformation, as well as bile duct proliferation.
BAS defect type 3 is caused by mutations in the 7-alpha hydroxylase gene (CYP7B1, 8q21.3). The deficiency in oxysterol 7alpha-hydroxylation leads to the accumulation of hepatotoxic unsaturated monohydroxy bile acids. The mode of transmission is presumed to be autosomal recessive.
Diagnosis, based on analysis of urine using liquid secondary ionization mass spectrometry (LSIMS) shows sulfate and glycosulfate conjugates of unsaturated monohydroxy-cholenoic acids (3beta-hydroxy-5-cholenoic and 3beta-hydroxy-5-cholestenoic acids) and an absence of primary bile acids.
Management and treatment
This anomaly of bile acid synthesis is particularly severe and is not treatable by primary bile acid therapy.