Comprehensive Urinary Bile Acid Profiling in Patients Investigated for Inborn Errors of Bile Acid Synthesis Using LC–MS/MS
Metabolites, cilt.16, sa.10, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16 Sayı: 10
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/metabo16100753
- Dergi Adı: Metabolites
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest)
- Anahtar Kelimeler: bile acids, cholestatic liver disease, inborn errors of bile acid synthesis, tandem mass spectrometry, targeted bile acid profiling
- Hacettepe Üniversitesi Adresli: Evet
Özet
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.