scholarly journals Genetic spectrum and clinical characteristics of 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency in China

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jing Zhao ◽  
Kenneth D. R. Setchell ◽  
Ying Gong ◽  
Yinghua Sun ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Bile Acid ◽  
Renal Cysts ◽  
Renal Stones ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Calcium Deposition ◽  
Clinical Feature ◽  
Acid Therapy ◽  
Renal Lesions

Abstract Background Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. The goal of this study was to obtain detailed information on the correlation between the genotype and phenotype of HSD3B7 deficiency and to report on responses to primary bile acid therapy. Methods The medical records of a cohort of 39 unrelated patients with genetically and biochemically confirmed HSD3B7 deficiency were examined to determine whether there exist genotype-phenotype relationships in this bile acid synthesis disorder. Results In all, 34 of the 44 variants identified in HSD3B7 were novel. A total of 32 patients presented early with neonatal cholestasis, and 7 presented after 1-year of age with liver failure (n = 1), liver cirrhosis (n = 3), cholestasis (n = 1), renal cysts and abnormal liver biochemistries (n = 1), and coagulopathy from vitamin K1 deficiency and abnormal liver biochemistries (n = 1). Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 of 35 patients. Thirty-three patients were treated with oral chenodeoxycholic acid (CDCA) resulting in normalization of liver biochemistries in 24, while 2 showed a significant clinical improvement, and 7 underwent liver transplantation or died. Remarkably, renal lesions in 6 patients resolved after CDCA treatment, or liver transplantation. There were no significant correlations between genotype and clinical outcomes. Conclusions In what is the largest cohort of patients with HSD3B7 deficiency thus far studied, renal lesions were a notable clinical feature of HSD3B7 deficiency and these were resolved with suppression of atypical bile acids by oral CDCA administration.

Genetic Spectrum and Clinical Characteristics of 3β-hydroxy-Δ5-C27-steroid Oxidoreductase (HSD3B7) Deficiency in China

2021 ◽  
Author(s):  
Jing Zhao ◽  
Kenneth DR Setchell ◽  
Ying Gong ◽  
Yinghua Sun ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Renal Cysts ◽  
Clinical Information ◽  
Renal Stones ◽  
Calcium Deposition ◽  
Clinical Feature ◽  
Renal Lesions ◽  
Significant Clinical Improvement ◽  
Renal Enlargement ◽  
One Year

Abstract Background Biallelic variants in HSD3B7 cause 3β-hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a life-threatening but treatable liver disease. Genetic and correlated clinical information is limited. We retrospectively reviewed the records of 39 unrelated patients with genetically confirmed HSD3B7 deficiency. Results In this cohort, 44 variants (34 novel) of HSD3B7 were detected. 31 patients were referred before one year old for neonatal cholestasis. eight patients were referred after one year old for liver failure (n=2), liver cirhosis (n=3), cholestasis (n=1), renal cysts and abnormal liver biochemistries (n=1), coagulopathy of vitamin K1 deficiency and abnormal liver biochemistries (n=1) respectively. Renal lesions, including renal cysts, renal stones, calcium deposition and renal enlargement were observed in 10 out of 35 patients with available data. 33 patients received oral chenodeoxycholic acid (CDCA) administration, 22 achieved normalization of liver biochemistries, five showed significant clinical improvement, six underwent liver transplantation or died. Renal lesions in six patients resolved after CDCA administration or liver transplantation. There is no significant correlation between genotype and clinical outcome. Conclusions This is so far the largest cohort of HSD3B7 deficiency, and reveals thatrenal lesion is a notable clinical feature of HSD3B7 deficiency and can be resolved with suppression of atypical bile acids.

scholarly journals Tandem Mass Spectrometric Determination of Atypical 3β-Hydroxy-Δ5-Bile Acids in Patients with 3β-Hydroxy-Δ5-C27-Steroid Oxidoreductase Deficiency: Application to Diagnosis and Monitoring of Bile Acid Therapeutic Response

2015 ◽  
Vol 61 (7) ◽  
pp. 955-963 ◽  
Author(s):  
Wujuan Zhang ◽  
Pinky Jha ◽  
Brian Wolfe ◽  
Antimo Gioiello ◽  
Roberto Pellicciari ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Tandem Mass ◽  
Acid Therapy ◽  
Bile Acid Therapy ◽  
Primary Bile Acid

AbstractBACKGROUND3β-Hydroxy-Δ5-C27-steroid oxidoreductase (HSD3B7) deficiency, a progressive cholestatic liver disease, is the most common genetic defect in bile acid synthesis. Early diagnosis is important because patients respond to oral primary bile acid therapy, which targets the negative feedback regulation for bile acid synthesis to reduce the production of hepatotoxic 3β-hydroxy-Δ5-bile acids. These atypical bile acids are highly labile and difficult to accurately measure, yet a method for accurate determination of 3β-hydroxy-Δ5-bile acid sulfates is critical for dose titration and monitoring response to therapy.METHODSWe describe a electrospray ionization LC-MS/MS method for the direct measurement of atypical 3β-hydroxy-Δ5-bile acid sulfates in urine from patients with HSD3B7 deficiency that overcomes the deficiencies of previously used GC-MS methods.RESULTSSeparation of sulfated 3β-hydroxy-Δ5-bile acids was achieved by reversed-phase HPLC in a 12-min analytical run. The mean (SE) urinary concentration of the total 3β-sulfated-Δ5-cholenoic acids in patients with HSD3B7 deficiency was 4650 (1711) μmol/L, approximately 1000-fold higher than in noncholestatic and cholestatic patients with intact primary bile acid synthesis. GC-MS was not reliable for measuring 3β-hydroxy-Δ5-bile acid sulfates; however, direct analysis of urine by fast atom bombardment mass spectrometry yielded meaningful semiquantitative assessment of urinary excretion.CONCLUSIONSThe tandem mass spectrometry method described here for the measurement of 3β-hydroxy-Δ5-bile acid sulfates in urine can be applied to the diagnosis and accurate monitoring of responses to primary bile acid therapy in HSD3B7 patients.

scholarly journals Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women

2012 ◽  
Vol 32 (3) ◽  
pp. 810-814 ◽  
Author(s):  
Lena Persson ◽  
Peter Henriksson ◽  
Eli Westerlund ◽  
Outi Hovatta ◽  
Bo Angelin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Lower Plasma

scholarly journals Bile Acid Synthesis Disorders in Japan: Long-Term Outcome and Chenodeoxycholic Acid Treatment

2021 ◽  
Author(s):  
Akihiko Kimura ◽  
Tatsuki Mizuochi ◽  
Hajime Takei ◽  
Akira Ohtake ◽  
Jun Mori ◽  
...  
Keyword(s):  
Bile Acid ◽  
Chenodeoxycholic Acid ◽  
Acid Treatment ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Manipulating the Microbiome: An Alternative Treatment for Bile Acid Diarrhoea

2021 ◽  
Vol 12 (2) ◽  
pp. 335-353
Author(s):  
Evette B. M. Hillman ◽  
Sjoerd Rijpkema ◽  
Danielle Carson ◽  
Ramesh P. Arasaradnam ◽  
Elizabeth M. H. Wellington ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Gastrointestinal Disease ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
The United Kingdom ◽  
The 1960S ◽  
Irritable Bowel ◽  
The Uk

Bile acid diarrhoea (BAD) is a widespread gastrointestinal disease that is often misdiagnosed as irritable bowel syndrome and is estimated to affect 1% of the United Kingdom (UK) population alone. BAD is associated with excessive bile acid synthesis secondary to a gastrointestinal or idiopathic disorder (also known as primary BAD). Current licensed treatment in the UK has undesirable effects and has been the same since BAD was first discovered in the 1960s. Bacteria are essential in transforming primary bile acids into secondary bile acids. The profile of an individual’s bile acid pool is central in bile acid homeostasis as bile acids regulate their own synthesis. Therefore, microbiome dysbiosis incurred through changes in diet, stress levels and the introduction of antibiotics may contribute to or be the cause of primary BAD. This literature review focuses on primary BAD, providing an overview of bile acid metabolism, the role of the human gut microbiome in BAD and the potential options for therapeutic intervention in primary BAD through manipulation of the microbiome.

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