Screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios
AssigneeAcademisch Medisch Centrum
InventorFrederic Maxime Vaz
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Abstract
The invention relates to a method of diagnosing or screening for 27-hydroxylase (CYP27A1) deficiency in an animal comprising: determining in a biological sample the intensity signal by mass analysis of at least a bile alcohol glucuronide and a C24- or C27-bile acid or a conjugate thereof, comparing the intensity signals to a control sample or control value, and determining 27-hydroxylase (CYP27A1) deficiency based on said comparison.
Claims11
A method of identifying 27-hydroxylase (CYP27A1) deficiency in an animal, the method comprising:
- receiving a dried blood spot comprising a blood sample from said animal;
- enriching the blood sample by liquid chromatography, protein precipitation, liquid-liquid extraction, solid-liquid extraction, or ultrafiltration;
- detecting, by mass analysis of the enriched blood sample, an intensity signal of at least a bile alcohol glucuronide and a C27- or C24-bile acid or a conjugate thereof, wherein the C27- or C24-bile acid or conjugate thereof is selected from the group consisting of:
- cholic acid (CA), tauro-cholic acid (t-CA);
- glyco-cholic acid (g-CA);
- chenodeoxycholic acid (CDCA);
- tauro-chenodeoxycholic acid (t-CDCA);
- glyco-chenodeoxycholic acid (g-CDCA);
- trihydroxycholestanoic acid (THCA);
- tauro-trihydroxycholestanoic acid (t-THCA);
- glyco-trihydroxycholestanoic acid (g-THCA);
- dihydroxycholestanoic acid (DHCA);
- tauro-dihydroxycholestanoic acid (t-DHCA);
- and glyco-dihydroxycholestanoic acid (g-DHCA);
- calculating a ratio between the intensity signals of said bile alcohol glucuronide and said C24- or C27-bile acid or conjugate thereof;
- comparing said ratio between the intensity signals of said bile alcohol glucuronide and said C24- or C27-bile acid or conjugate thereof with a ratio of a control sample or control value from a control animal of the same species as the animal but without CYP27A1 deficiency;
- and
- identifying the animal as having hydroxylase (CYP27A1) deficiency, based on said comparison of said ratios.
A kit comprising a stable isotope labeled C24- or C27-bile acid or a conjugate thereof selected from the group consisting of:
- cholic acid (CA), tauro-cholic acid (t-CA), glyco-cholic acid (g-CA), chenodeoxycholic acid (CDCA), tauro-chenodeoxycholic acid (t-CDCA), glyco-chenodeoxycholic acid (g-CDCA), trihydroxycholestanoic acid (THCA), tau ro-trihydroxycholestanoic acid (t-THCA), glyco-trihydroxycholestanoic acid (g-THCA), dihydroxycholestanoic acid (DHCA), tauro-dihydroxycholestanoic acid (t-DHCA), and glyco-dihydroxycholestanoic acid (g-DHCA);
- and
- further comprising a positive control sample, wherein the positive control sample is a dried blood spot comprising a blood sample from a control animal of the same species as the animal but with cerebrotendinous xanthomatosis (CTX).
Dependencies are inferred from the claim text.