| Defect / type | Gene | OMIM in evidence | Typical presentation notes | Key diagnostic test | Typical treatment | Key quantitative outcomes / doses |
|---|---|---|---|---|---|---|
| Aggregate concept: inborn disorders of bile acid synthesis/metabolism; synonyms include IEBAM, IEBAS, BASD (pqac-00000018, pqac-00000019, pqac-00000023) | Multiple: HSD3B7, SRD5B1/AKR1D1, CYP7B1, CYP27A1, BAAT, SLC27A5, AMACR, CYP7A1 (pqac-00000018, pqac-00000016) | HSD3B7 607765; SRD5B1 235555; CYP27A1 213700; CYP7B1 603711; BAAT/BACD1 619232; AMACR 604489; additional gene OMIMs in evidence include AKR1D1 604741, CYP7A1 118455, SLC27A5 603314 (pqac-00000018, pqac-00000016, pqac-00000017) | Usually neonatal/infantile cholestasis with normal or low GGT and normal/low serum total bile acids; often absent pruritus; fat-soluble vitamin deficiency/bleeding; some defects later show neurologic disease (pqac-00000000, pqac-00000005, pqac-00000010) | Urinary bile acid profiling by LC-MS or GC-MS plus confirmatory genetic testing; STBA and GGT help distinguish from biliary atresia; newborn dried-blood-spot metabolite screening is emerging (pqac-00000000, pqac-00000004, pqac-00000007) | Primary bile acid replacement, mainly cholic acid or chenodeoxycholic acid; defect-specific exceptions apply; liver transplantation for severe failure (pqac-00000000, pqac-00000001, pqac-00000010) | IEBAM may account for ~2% of cholestasis of unknown cause; open-label cholic acid trials used 10–15 mg/kg/day; Japanese BASD prevalence among 1010 unexplained cholestasis cases was 0.7% (pqac-00000006, pqac-00000001, pqac-00000008) |
| 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase deficiency (3β-HSD deficiency) (pqac-00000018, pqac-00000019) | HSD3B7 (pqac-00000018, pqac-00000021) | 607765 in evidence (pqac-00000018, pqac-00000019) | Cholestatic jaundice, acholic/fatty stools, failure to thrive, fat-soluble vitamin deficiency; often low/normal GGT and low/normal STBA (pqac-00000007, pqac-00000000, pqac-00000010) | Urine/serum bile acid profiling showing high atypical 3β-hydroxy-Δ5 bile acids; sequencing of HSD3B7 (pqac-00000007, pqac-00000000) | Cholic acid standard; alternative bile acid approaches reported when needed, including glycodeoxycholic acid case use (pqac-00000001, pqac-00000002, pqac-00000010) | In long-term CA cohort including 13 HSD3B7 patients, mean daily CA dose 6.9 mg/kg/day and fibrosis improved/disappeared after 10–24 years; gDCA case restored normal bile acid levels and improved weight without liver toxicity (pqac-00000010, pqac-00000009) |
| Δ4-3-oxosteroid 5β-reductase deficiency (5β-reductase deficiency; Δ4-3-oxo-R) (pqac-00000010, pqac-00000019) | SRD5B1 / AKR1D1 (pqac-00000018, pqac-00000019, pqac-00000021) | 235555 for disorder; AKR1D1 gene OMIM 604741 in evidence set (pqac-00000018, pqac-00000016) | Usually severe neonatal cholestasis, sometimes severe bleeding and liver failure; can be variable, including minimally symptomatic mutation carriers; pruritus often absent; GGT/TBA often normal or slightly raised (pqac-00000005, pqac-00000010) | Urinary bile acid LC-MS/GC-MS showing 3-oxo-Δ4 derivatives and allo-bile acids; AKR1D1/SRD5B1 sequencing (pqac-00000005, pqac-00000010) | Cholic acid preferred; UDCA may partially improve before diagnosis; some Japanese patients treated long-term with CDCA where CA unavailable (pqac-00000010, pqac-00000008) | In 16 CA-treated patients: median onset 2 months, CA started median 8.1 months, liver tests normalized in all within 6–12 months, median last dose 8.3 mg/kg/day, 12-fold urinary metabolite decrease, all alive with native liver after median 4.5 years; 15/16 had prior UDCA with partial improvement in 8 (pqac-00000010) |
| Oxysterol 7α-hydroxylase deficiency / congenital bile acid synthesis defect type 3 (pqac-00000018, pqac-00000019) | CYP7B1 (pqac-00000018, pqac-00000021) | 603711 in evidence (pqac-00000018, pqac-00000019) | Severe infantile progressive cholestasis/liver failure in infancy; can also present later with hereditary spastic paraplegia phenotype, even within the same family (pqac-00000011) | Urinary bile acid analysis showing atypical hepatotoxic 3β-hydroxy-Δ5 bile acids; CYP7B1 genetic testing (pqac-00000011, pqac-00000007) | Chenodeoxycholic acid; liver transplantation when progressive failure is advanced (pqac-00000011, pqac-00000015) | Case evidence: CDCA begun while awaiting transplant led to rapid liver improvement and normalized urine atypical bile acids by follow-up at 23 months; in Japanese cohort 1 patient required liver transplantation and later recovered (pqac-00000011, pqac-00000015) |
| α-Methylacyl-CoA racemase deficiency / BASD type 4 (pqac-00000022) | AMACR (pqac-00000022) | 604489 in evidence (pqac-00000017) | Neonatal cholestasis or later slowly progressive adult neurologic disease with retinitis pigmentosa, neuropathy, ataxia, cognitive decline; risk of liver fibrosis/cirrhosis/HCC (pqac-00000022, pqac-00000014) | Urine metabolite testing and/or serum C27 bile acid intermediates with genetic confirmation; MRI may support adult diagnosis (pqac-00000022, pqac-00000014) | Oral cholic acid plus diet modification reported; CA also represented in systematic review data (pqac-00000022, pqac-00000014) | Fewer than 20 cases in prior literature; 2024 cohort described 12 genetically confirmed patients, median diagnosis age 56 years, mean follow-up 6 years, retinitis pigmentosa in 5/9 adults, neurologic symptoms in all adults after age 40 (pqac-00000014) |
| Sterol 27-hydroxylase deficiency / cerebrotendinous xanthomatosis (CTX) (pqac-00000018, pqac-00000016) | CYP27A1 (pqac-00000018) | 213700 in evidence (pqac-00000018) | Systemic disease with bile acid deficiency and cholestanol/bile alcohol accumulation; neurologic sequelae dominate, rather than neonatal cholestasis in most cases (pqac-00000018, pqac-00000014) | Biochemical profiling of cholestanol/bile alcohols and genetic testing (pqac-00000014) | Chenodeoxycholic acid standard in CTX; CA represented in systematic review but defect-specific standard remains CDCA (pqac-00000014) | CA systematic review included 22 CTX patients; separate cohort evidence for CDCA shows long-term biochemical and clinical improvement in many patients (pqac-00000014) |
| Bile acid amidation / conjugation defects (bile acid conjugation defect-1) (pqac-00000017, pqac-00000016) | BAAT; related ligase defect SLC27A5 (pqac-00000017, pqac-00000016) | BACD1/BAAT 619232; SLC27A5 gene OMIM 603314 in evidence (pqac-00000017, pqac-00000016) | Neonatal cholestasis with fat-soluble vitamin malabsorption; unconjugated bile acids and compensatory urinary sulfate/glucuronide conjugates; GGT may remain normal (pqac-00000003, pqac-00000017) | Specialized bile acid profiling showing unamidated bile acids; confirmatory sequencing (pqac-00000016, pqac-00000017) | Glycocholic acid/conjugated cholic acid; UDCA may be considered in some related defects (pqac-00000002, pqac-00000000) | Phase 3 glycocholic acid study enrolled 5 patients and used 10–15 mg/kg/day, with outcomes including liver tests, bile acid profiles, vitamin absorption, growth, and histology (pqac-00000002) |


*Table: This table summarizes the main inborn bile acid synthesis/metabolism defects represented in the retrieved evidence, including genes, OMIM identifiers, presentations, diagnostics, treatments, and key quantitative outcomes. It is useful as a compact reference for comparing subtype-specific clinical and management features.*