Comprehensive Urinary Bile Acid Profiling in Patients Investigated for Inborn Errors of Bile Acid Synthesis Using LC–MS/MS

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Abstract
Background/Objectives: This study examined urinary cholanoid profiles in a descriptive case series evaluated for suspected inborn errors of bile acid synthesis (IEBAS) or unexplained cholestasis. Methods: Urinary excretion of 66 bile acid metabolites was measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS), and concentrations were interpreted as semi-quantitative estimates. In addition, cholesterol, cholestanol, and 7-dehydrocholesterol were analyzed by gas chromatography–mass spectrometry (GC-MS). Results: Five patients had genetically confirmed IEBAS: 3β-hydroxy-Δ5-C27-steroid dehydrogenase (HSD3B7) deficiency in 2 patients and cerebrotendinous xanthomatosis (CTX) in 3 patients. Two patients were subsequently diagnosed with biliary atresia and progressive familial intrahepatic cholestasis type 1. Other patients remained without a definitive etiological diagnosis. Of the two patients with genetically confirmed HSD3B7 deficiency, patient 1 showed a predominance of 3β-hydroxy-Δ5 bile acids (63.9% of total urinary bile acids), including sulfated dihydroxy-, glycine-conjugated dihydroxy-, and trihydroxy-Δ5 species. Patient 2 had an atypical urinary bile acid profile, with the 3β-hydroxy-Δ5 fraction dominated by a monohydroxy species. CTX patients had profiles with a different bile acid group composition; hydroxylated bile acids were reported in 2 patients, whereas no numerical result was reported for 1 patient. The 3β-hydroxy-Δ5 bile acid levels in 1 CTX patient were within the observed control range. Two patients also had differential profiles for hydroxylated and 3β-hydroxy-Δ5 bile acids, which provided biochemical findings for further etiological evaluation. The species assigned to glycoursodeoxycholic acid predominated in the urinary profiles of the five patients receiving ursodeoxycholic acid. Conclusions: Urinary cholanoid profiling may provide complementary biochemical information alongside the available clinical and genetic findings in the evaluation of suspected IEBAS.
Funding Information
  • Hacettepe Üniversitesi (THD-2018-16921)

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