Comprehensive Urinary Bile Acid Profiling in Patients Investigated for Inborn Errors of Bile Acid Synthesis Using...

This study examined urinary cholanoid profiles in a descriptive case series evaluated for suspected inborn errors of bile acid synthesis (IEBAS) or unexplained cholestasis.

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).

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.

Urinary cholanoid profiling may provide complementary biochemical information alongside the available clinical and genetic findings in the evaluation of suspected IEBAS.