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

Table 1 Inherited defects of cholesterol biosynthesis in humans

Disorder	OMIM#	Frequency	Enzyme (blood biomarkers)	Primary site of expression	Treatable	Ref.
SLOS	270400	1:20000/1:50000	7-dehydrocholesterol reductase (7-dehydrocholesterol, 8-dehydrocholesterol)	Multisystemic	Yes	[28,36]
					Mild cases
Desmosterolosis	602398	9 cases	3β-hydroxysterol-∆24-reductase (desmosterol)	Multisystemic	No	[25,37]
CDPX21	302960	≤ 1:400000	3β-hydroxysteroid-∆8,∆7-sterol isomerase [8-dehydrocholesterol, cholesta-8(9)-en-3β-ol]	Skin and skeletal systems	No	[25,38]
CHILD syndrome	308050	< 1:1000000	3β-hydroxysteroid dehydrogenase [4α-carboxymethylcholest-8(9)-en-3β-ol, 4α-monomethyl-and 4,4’-dimethylsterols]2	Skin and skeletal systems	No	[25,39]
Lathosterolosis	607330	4 cases	3β-hydroxysteroid-∆5-desaturase (lathosterol)	Multisystemic	Yes	[40-43]
					Two cases
Antley-Bixler syndrome3	201750	> 100 cases	Lanosterol 14α-demethylase (lanosterol, dihydrolanosterol)2	Skin and genital systems	No	[44,45]
Greenberg dysplasia	215140	11 cases	Sterol-∆14-reductase (cholesta-8,14-dien-3β-ol, cholesta-8,14,24-trien-3β-ol)2	Skeletal system	No	[25,46]
CK syndrome	300831	13 cases	3β-hydroxysteroid dehydrogenase (4α-monomethyl- and 4,4’-dimethylsterols)2	Nervous system	No	[25,47,48]
SC4MOL deficiency	616834	5 cases	Sterol-C4-methyl oxidase (4α-monomethyl- and 4,4’-dimethylsterols)	Skin and eye	Yes	[49,50,88]
				Systems	One case

¹An hypomorphic variant (#300960) has been reported in 10 male patients[25,51];

²Presence of biomarkers in tissue and/or cultured cells only;

³A variant form (#613571) due to deficiency of cytochrome P450 oxidoreductase has been reported 9 subjects[45,52]. CDPX2: X-linked dominant disorder chondrodysplasia punctata-2; CHILD: Congenital hemidysplasia with ichthyosiformerythroderma and limb defects; CK: Eponym derived from the first case; SC4MOL: Sterol-C4-methyl oxidase; SLOS: Smith-Lemli-Opitz syndrome.