Liver and the defects of cholesterol and bile acids biosynthesis: Rare disorders many diagnostic pitfalls

Table 3 Clinical and laboratory findings shared by some treatable defects of cholesterol and bile acid biosynthesis

Clinical features	SLOS1	LATHO	SC4MOL	CTX	CBAS1	CBAS2	CBAS4	Shared findings
Microcephaly	Yes	Yes	Yes	No	No	No	No	3/7
Congenital cataracts	Yes	Yes	Yes	Yes	No	No	No	4/7
Intellectual disability	Yes	Yes	Yes	Yes	No	No	No	4/7
Neurological disease	No	No	No	Yes	No	No	Yes	2/7
Developmental delay	Yes	Yes	Yes	No	No	No	No	3/7
Cholestasis	No	Yes	No	Yes	Yes	Yes	Yes	5/7
Steatosis	No	Yes	No	No	No	Yes	No	2/7
AST	Normal	High	Normal	High	High	High	Normal	4/7
ALT	Normal	High	Normal	High	High	High	Normal	4/7
γGT	Normal	High	Normal	Normal	Normal	High	Normal	2/7
Conjugated bilirubin	Normal	High	Normal	High	High	High	Normal	4/7
Total cholesterol	Very low to normal	Low to normal	Low to normal	Normal to high	Normal	Normal	Normal	n.a.
Fat-soluble vitamin	Normal	Low	Normal	Normal	Low	Low	Low	4/7
Diagnostic method
GC-MS	Sterols (p)	Sterols (p)	Sterols (p)	Sterols (p)
LC-MS/MS				HBA (u)	BA (u)	BA (u, p)	BA (u, p)
Treatment	Cholesterol plus statins	Statins or LT	Cholesterol plus statins and bile acids	CDCA plus statins	Cholic acid	UDCA or cholic acid	Cholic acid2

¹Mild phenotypes;

²Associated with a phytanic/pristanic acid-restricted diet. BA: Bile acids; CDCA: Chenodeoxycholic acid; HBA: Hydroxy bile alcohols; LATHO: Lathosterolosis; LT: Liver transplant; n.a.: Not applicable; (p): Plasma; (u): Urine; UDCA: Ursodeoxycholic acid. GC-MS: Gas chromatography coupled to mass spectrometry; LC-MS/MS: Liquid chromatography coupled to tandem mass spectrometry.