Differential diagnosis in patients with suspected bile acid synthesis defects

Table 1 Reference ranges of bile acid metabolites which accumulate in different bile acid biosynthesis defects

Defect	Metabolite	m/z	Median	Range
3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency	Glyco-dihydroxy-5-cholenoic acid	526	0.05	0.0-0.9
HSD3B7	Glyco-trihydroxy-5-cholenoic acid	542	0.07	0.0-0.4
16p11.2-12	Dihydroxy-5-cholenoic acid sulphate	469	0.71	0.15-8.1
OMIM: 23110	Trihydroxy-5-cholenoic acid sulphate	485	0.08	0.0-2.0
Δ4-3-oxosteroid 5-β-reductase deficiency	Glyco-hydroxy-oxo-cholenoic acid	444	0.03	0.0-0.4
AKR1D1	Glyco-dihydroxy-oxo-cholenoic acid	460	0.04	0.0-2.4
7q31	Tauro-hydroxy-oxo-cholenoic acid	494	0.02	0.0-0.5
OMIM: 235555	Tauro-dihydroxy-oxo-cholenoic acid	510	0.04	0.0-5.0
Defects of peroxisomal biogenesis	Tauro-tri-hydroxycholestanoic acid	556	0.02	0.0-0.3
Multiple	Tauro-tetra-hydroxycholestanoic acid	572	0.02	0.0-0.2
OMIM: 214100
Sterol 27-hydroxylase deficiency	Glucuronide-5β-cholestane-tetrol	611	0.24	0.0-1.6
(cerebrotendinous xanthomatosis)	Glucuronide-5β-cholestane-pentol	627	0.37	0.1-4.3
CYP27A1
2q33-qter
OMIM: 213700
Cholestatic liver disease	Glyco-chenodeoxy-cholic acid	448	0.49	0.0-5.2
Multiple	Glyco-cholic acid	464	0.64	0.1-14.6
	Tauro-chenodeoxy-cholic acid	498	0.05	0.0-0.8
	Tauro-cholic acid	514	0.08	0.0-8.4

The disorders are listed with their Online Mendelian Inheritance in Man^TM (OMIM) and their genetic defect, respectively. Reference ranges for bile acid metabolites which are increased in different bile acid synthesis defects were established in 100 healthy children, adolescents and young adults of age 10 d to 20 years. The metabolites are arranged to their appearance in different pathological conditions. Data are peak area ratios obtained for conjugates versus internal standard normalized to mol creatinine. The characteristic fragment ions used for detection of the metabolites are given as the mass-to-charge ratio (m/z).