RARE DISEASE
Congenital bile acid synthesis defect type 1
Congenital bile acid synthesis defect type 1
Congenital bile acid synthesis defect type 1
Synonyms: 3-beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency, BASD1
Synonyms: 3-beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency, BASD1
Synonyms: 3-beta-hydroxy-delta-5-C27-steroid oxidoreductase deficiency, BASD1
Drug discovery
0
drugs
With orphan designations
Overview
Congenital bile acid synthesis defect type 1 (CBAS1) is an autosomal recessive disorder caused by mutations in HSD3B7, disrupting bile acid production from cholesterol. It manifests with neonatal cholestasis, hepatomegaly, jaundice, and fat-soluble vitamin malabsorption, often progressing to cirrhosis without treatment. Diagnosis involves urinary mass spectrometry to detect atypical 3β-hydroxy-Δ5 bile acids. Early oral cholic acid therapy suppresses toxic intermediates, restores bile flow, and halts disease progression [1][2][6][8].
Categories: rare genetic diseases, rare hepatic diseases, rare inborn errors of metabolism, rare transplant-related disorders
Research Papers
17 drug discovery papers about Congenital bile acid synthesis defect type 1, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
17 drug discovery papers about Congenital bile acid synthesis defect type 1, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2025-12-19 | The Diagnostic Odyssey of Congenital Bile Acid Synthesis Defect Type 1: A Case Report
Congenital Bile Acid Synthesis Defects (BASDs) are rare, autosomal recessive metabolic conditions defined by defects in primary bile acid synthesis, leading to the accumulation of toxic intermediate sterols, a deficiency of normal primary bile acids (cholic and chenodeoxycholic acid), and subsequent cholestasis and fat-soluble vitamin malabsorption. Early diagnosis and targeted replacement therapy are vital to prevent progressive liver damage and fatal outcomes. This report describes a 6-year and 5-monthold male from a consanguineous marriage in Chennai, presenting late with right arm swelling, gum bleeding, and progressive pallor for one week. He had a significant history of neurodevelopmental delay and a sibling’s death from jaundice. Physical examination revealed severe malnutrition, icterus, widespread ecchymoses, ichthyosis, and spastic quadriparesis. Blood investigations confirmed severe microcytic hypochromic anaemia (Hb 1.6 g/dL) and severe coagulopathy {Prothrombin Time (PT)> 100, International Normalised Ratio (INR)>8}. A diagnosis of congenital BASD type 1 was established through abnormal urinary bile acid profiling Fast Atom Bombardment–Mass Spectrometry (FAB-MS) and was confirmed by genetic testing showing biallelic pathogenic variants in the HSD3B7 gene. The child was managed with aggressive supportive care, including blood and Fresh Frozen Plasma (FFP) transfusions and high-dose Vitamin K, alongside targeted therapy with oral cholic acid and fat-soluble vitamins. The child showed dramatic clinical improvement within six days, reinforcing the therapeutic benefit of even delayed intervention, although liver transplantation was advised for the advanced liver disease. This case underscores the challenges of late diagnosis and the lifethreatening coagulopathy associated with severe BASD type 1.
2023-04-18 | Bile Acid Synthesis Disorder, the First Reported Case from Iran, (Proven by Genetic Study), How the Unavailability of Drug Affected the Course of Treatment
Introduction: Bile acid synthesis disorder is a very rare autosomal recessive disorder, which is mainly diagnosed by detecting mutations in the genes encoding enzymes that are involved in bile metabolism, including Δ4-3-oxosteroid-5β-reductase and 3β-Δ5-hydroxy-C27-steroid oxidoreductase. The enzymatic impairments can result in the accumulation of atypical and hepatotoxic bile acid intermediates, which clinically lead to cholestasis and progress to cirrhosis and hepatic failure. Herein, we describe a case of bile acid synthesis disorder diagnosed using molecular genetic assessment. Case Presentation: A 7-year-old girl is presented with failure to thrive since early in life. She had a history of urinary tract infection at four years of age. The sonography was performed at that time and revealed renal microcalculi. She also had a history of abdominal pain, nausea, and vomiting. She underwent upper endoscopies three times to rule out celiac disease; nevertheless, duodenal biopsies were all reported as normal. Muscle weakness was detected at five years of age and electromyography and muscle biopsy findings were non-specific. She underwent a whole-genome study and was diagnosed with bile acid synthesis disorder (BASD). After six months, she was treated with ursodeoxycholic acid, 250 mg, which led to growth compensation and liver enzyme reduction. No adverse effect was reported during the treatment. Conclusions: Bile acid synthesis disorder is a rare disorder with non-specific features and several organ involvements. It may take several years to achieve the correct diagnosis. To our knowledge, this is the first genetically confirmed case of bile acid synthesis disorder reported in Iran.
2019-11-20 | Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives
Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.
2019-05-31 | Bile acid synthesis defect (5B-reductase deficiency) a rare cause of cholestasis in an infant
Bile acid synthesis disorders (BASD) are rare inborn errors of metabolism and its presentation includes- neonatal cholestasis, neurologic disease or deficiency of fat-soluble-vitamins. 1The trait features of these diseases are failure to produce normal bile acids, which leads to accumulation of unusual bile acids and bile acid intermediaries in liver and blood. Pathophysiological manifestations are due to deficiency of bile acids in gastrointestinal tract and accumulation of bile acid intermediates. Delay in initiating treatment can result in progressive chronic liver disease and liver failure. Bile acid therapy can lead to remarkable clinical response, if disorder is recognized earlier and liver transplant can be averted. Here we present an infant with cholestatic jaundice with chronic liver disease and subdural hematoma who was diagnosed to have 5 beta reductase deficiency.
2018-09-19 | Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature.
Steroid 5β-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
small molecules
2025-12-19 | The Diagnostic Odyssey of Congenital Bile Acid Synthesis Defect Type 1: A Case Report
Congenital Bile Acid Synthesis Defects (BASDs) are rare, autosomal recessive metabolic conditions defined by defects in primary bile acid synthesis, leading to the accumulation of toxic intermediate sterols, a deficiency of normal primary bile acids (cholic and chenodeoxycholic acid), and subsequent cholestasis and fat-soluble vitamin malabsorption. Early diagnosis and targeted replacement therapy are vital to prevent progressive liver damage and fatal outcomes. This report describes a 6-year and 5-monthold male from a consanguineous marriage in Chennai, presenting late with right arm swelling, gum bleeding, and progressive pallor for one week. He had a significant history of neurodevelopmental delay and a sibling’s death from jaundice. Physical examination revealed severe malnutrition, icterus, widespread ecchymoses, ichthyosis, and spastic quadriparesis. Blood investigations confirmed severe microcytic hypochromic anaemia (Hb 1.6 g/dL) and severe coagulopathy {Prothrombin Time (PT)> 100, International Normalised Ratio (INR)>8}. A diagnosis of congenital BASD type 1 was established through abnormal urinary bile acid profiling Fast Atom Bombardment–Mass Spectrometry (FAB-MS) and was confirmed by genetic testing showing biallelic pathogenic variants in the HSD3B7 gene. The child was managed with aggressive supportive care, including blood and Fresh Frozen Plasma (FFP) transfusions and high-dose Vitamin K, alongside targeted therapy with oral cholic acid and fat-soluble vitamins. The child showed dramatic clinical improvement within six days, reinforcing the therapeutic benefit of even delayed intervention, although liver transplantation was advised for the advanced liver disease. This case underscores the challenges of late diagnosis and the lifethreatening coagulopathy associated with severe BASD type 1.
2023-04-18 | Bile Acid Synthesis Disorder, the First Reported Case from Iran, (Proven by Genetic Study), How the Unavailability of Drug Affected the Course of Treatment
Introduction: Bile acid synthesis disorder is a very rare autosomal recessive disorder, which is mainly diagnosed by detecting mutations in the genes encoding enzymes that are involved in bile metabolism, including Δ4-3-oxosteroid-5β-reductase and 3β-Δ5-hydroxy-C27-steroid oxidoreductase. The enzymatic impairments can result in the accumulation of atypical and hepatotoxic bile acid intermediates, which clinically lead to cholestasis and progress to cirrhosis and hepatic failure. Herein, we describe a case of bile acid synthesis disorder diagnosed using molecular genetic assessment. Case Presentation: A 7-year-old girl is presented with failure to thrive since early in life. She had a history of urinary tract infection at four years of age. The sonography was performed at that time and revealed renal microcalculi. She also had a history of abdominal pain, nausea, and vomiting. She underwent upper endoscopies three times to rule out celiac disease; nevertheless, duodenal biopsies were all reported as normal. Muscle weakness was detected at five years of age and electromyography and muscle biopsy findings were non-specific. She underwent a whole-genome study and was diagnosed with bile acid synthesis disorder (BASD). After six months, she was treated with ursodeoxycholic acid, 250 mg, which led to growth compensation and liver enzyme reduction. No adverse effect was reported during the treatment. Conclusions: Bile acid synthesis disorder is a rare disorder with non-specific features and several organ involvements. It may take several years to achieve the correct diagnosis. To our knowledge, this is the first genetically confirmed case of bile acid synthesis disorder reported in Iran.
2019-11-20 | Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives
Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.
2019-05-31 | Bile acid synthesis defect (5B-reductase deficiency) a rare cause of cholestasis in an infant
Bile acid synthesis disorders (BASD) are rare inborn errors of metabolism and its presentation includes- neonatal cholestasis, neurologic disease or deficiency of fat-soluble-vitamins. 1The trait features of these diseases are failure to produce normal bile acids, which leads to accumulation of unusual bile acids and bile acid intermediaries in liver and blood. Pathophysiological manifestations are due to deficiency of bile acids in gastrointestinal tract and accumulation of bile acid intermediates. Delay in initiating treatment can result in progressive chronic liver disease and liver failure. Bile acid therapy can lead to remarkable clinical response, if disorder is recognized earlier and liver transplant can be averted. Here we present an infant with cholestatic jaundice with chronic liver disease and subdural hematoma who was diagnosed to have 5 beta reductase deficiency.
2018-09-19 | Infant cholestasis patient with a novel missense mutation in the AKR1D1 gene successfully treated by early adequate supplementation with chenodeoxycholic acid: A case report and review of the literature.
Steroid 5β-reductase [aldo-keto reductase family 1 member D1 (AKR1D1)] is essential for bile acid biosynthesis. Bile acid deficiency caused by genetic defects in AKR1D1 leads to life-threatening neonatal hepatitis and cholestasis. There is still limited experience regarding the treatment of this disease. We describe an infant who presented with hyperbilirubinemia and coagulopathy but normal bile acid and γ-glutamyltransferase. Gene analysis was performed using genomic DNA from peripheral lymphocytes from the patient, his parents, and his elder brother. The patient was compound heterozygous for c.919C>T in exon 8 and exhibited a loss of heterozygosity of the AKR1D1 gene, which led to an amino acid substitution of arginine by cysteine at amino acid position 307 (p.R307C). Based on these mutations, the patient was confirmed to have primary 5β-reductase deficiency. Ursodeoxycholic acid (UDCA) treatment did not have any effect on the patient. However, when we changed to chenodeoxycholic acid (CDCA) treatment, his symptoms and laboratory tests gradually improved. It is therefore crucial to supplement with an adequate dose of CDCA early to improve clinical symptoms and to normalize laboratory tests.
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