Pathology
A. anomalies of bile acid synthesis (congenital bile acid synthesis diseases) (HPID:157)
A-1. anomalies of the modification of the sterol nucleus of bile acids
The synthesis of primary bile acids from cholesterol occurs via 2 pathways: the classic neutral pathway involving cholesterol 7-alpha-hydroxylase (CYP7A1; MIM.118455), and the acidic pathway involving a distinct microsomal oxysterol 7-alpha-hydroxylase (CYP7B1, MIM.603711).
defect in cholesterol 7α-hydroxylase (CYP7A1 - MIM.118455)
- Cholesterol 7-alpha-hydroxylase is a microsomal cytochrome P450 that catalyzes the first step in bile acid synthesis.
defect in oxysterol 7α-hydroxylase (CYP7B1 - MIM.603711).
- The acidic pathway of synthesis of primary bile acids from cholesterol involves a distinct microsomal oxysterol 7-alpha-hydroxylase (CYP7B1, MIM.603711).
defect in 3β-hydroxy-C27-steroid dehydrogenase/isomerase
defect in δ-4-3-oxosteroid 5β-reductase
A-2. defects in the modification of the side-chain of bile acids
Several inborn errors affecting single enzymes involved in the modification of the cholesterol side-chain to produce C24 bile acids have been identified. Additionally, because β-oxidation of the side-chain occurs in peroxisomes, peroxisomal disorders can also affect bile acid synthesis, accompanying other manifestations typical of each syndrome.
defect in sterol 27-hydroxylase
defect in 25-hydroxylase
defect in alpha methylacyl-CoA racemase
peroxisomal diseases
Apart from AMACR, other peroxisomal enzymes involved in the beta-oxidation of the bile acid side-chain are branched-chain acyl-CoA oxidase, D-bifunctional protein and sterol carrier protein X (SCPx).
A-3. Defects in bile acid amidation (Defective bile acid conjugation) (HPID:15088)
Defective bile acid conjugation, which is characterized by a complete absence of glycine and taurine conjugates of bile acids in biological fluids and a predominance of unconjugated CA, with small proportions of sulfate and glucuronide conjugates, has been reported. (HPID:15088)
B. Anomalies of bile acid transport (HPID:15089)
Anomalies of bile acid transport joins the group of progressive familial intrahepatic cholestasis (PFICs): PFIC1, PFIC2, PFIC3
C. Secondary alterations in bile acid homeostasis
References
Bile acids: chemistry, physiology, and pathophysiology. Monte MJ, Marin JJ, Antelo A, Vazquez-Tato J. World J Gastroenterol. 2009 Feb 21;15(7):804-16. PMID: 19230041