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

Table 2 Inherited defects of bile acids biosynthesis in humans

Disorder	OMIM#	Frequency	Enzyme (urine biomarkers)1	Primary site of expression	Treatable	Ref.
CTX	213700	1:50000	Sterol 27-hydroxylase (tetrahydroxy-, pentahydroxy- and hexahydroxy-bile alcohols)2	Eye, central and peripheral nervous systems	Yes	[26,30,35]
CBAS1	607765	73 cases	3β-hydroxy-∆5-C27-steroid oxidoreductase (3β-hydroxy-∆5 bile acids)	Liver	Yes	[26,35,57,58]
CBAS2	235555	41 cases	∆4-3-oxosteroid 5β-reductase (∆4-3-oxo bile acids)	Liver	Yes	[35,59-65]
SPG5A	270800	31 cases	Oxysterol 7α-hydroxylase (27-hydroxycholesterol)3	Central and peripheral nervous systems	No	[66-69]
FHCA	607748	15 cases	BAAT4 (unconjugated cholic acid)3	Liver and intestine	Yes	[35,70,71]
CBAS4	214950	6 cases	α-methylacyl-CoA racemase (THCA)5	Liver, intestine and peripheral nervous systems	Yes	[35,72,73]
CBAS3	613812	3 cases	oxysterol 7α-hydroxylase (3β-hydroxy-5-cholenoic and 3β-hydroxy-5-cholestenoic acids)	Liver	No	[35,74,75]
BACL deficiency	NR	8 cases	Bile acid-CoA ligase (unconjugated cholic acid)3	Liver and intestine	No	[76]
CYP7A1 deficiency	NR	< 1:1000000	CYP7A1 (3β-hydroxy-5-cholenoic and 3β-hydroxy-5-cholestenoic acids, 27-hydroxycholesterol)6	Cardiovascular system	No	[35,77]

¹Conjugated form unless otherwise noted;

²Plasma and tissue accumulation of cholestanol and cholesterol precursors;

³Presence also in serum;

⁴FHCA can be due also to mutations in Tight junction protein-2 and Microsomal epoxide hydrolase-1 genes;

⁵Plasma and tissue accumulation of phytanic and pristanic acids;

⁶High plasma levels of total and LDL-cholesterol, and 27-hydroxycholesterol. BAAT: Bile acids-CoA aminoacid N-acyltransferase; CTX: Cerebrotendinous xanthomatosis; CYP7A1: Cholesterol 7α-hydroxylase; FHCA: Familial hypercholanemia; NR: Not reported; SPG5A: Spastic paraplegia-5A; THCA: 3α,7α,12α-trihydroxy-5β-cholestan-26-oic acid.