biliary acid synthetic diseases
Bile acid synthetic defects are uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants.
Diagnosis
analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS)
Etiology
Four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids.
In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild.
Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome.
Pathological findings
intralobular cholestasis with giant cell transformation
necrotic hepatocytes including giant cell forms
hepatitic injury confined to the portal limiting plate
smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bile ducts are usually spared.
Ultrastructure
nonspecific changes with the possible exception of unusual canalicular morphology
References
Bove KE, Heubi JE, Balistreri WF, Setchell KD. Bile acid synthetic defects and liver disease: a comprehensive review.
Pediatr Dev Pathol. 2004 Jul-Aug;7(4):315-34. PMID: 15383928