Tandem Mass Spectrometric Determination of Atypical 3-Hydroxy-Δ5-Bile Acids in Patients with 3-Hydroxy-Δ5-C27-Steroid Oxidoreductase Deficiency: Application to Diagnosis and Monitoring of Bile Acid Therapeutic Response

3Beta-hydroxy-5-C27-steroid oxidoreductase (HSD3B7) deficiency, a progressive cholestatic liver disease, is the most common genetic defect in bile acid synthesis. Early diagnosis is important because patients respond to oral primary bile acid therapy, which targets the negative feedback regulation for bile acid synthesis to reduce the production of hepatotoxic 3beta-hydroxy-5-bile acids. These atypical bile acids are highly labile and difficult to accurately measure, yet a method for accurate determination of 3-hydroxy-5-bile acid sulfates is critical for dose titration and monitoring response to therapy.