Cholic acid therapy in Zellweger spectrum disorders
| Autor: | Martin Lenicek, Femke C. C. Klouwer, Frank G. Schaap, Kiran V. K. Koelfat, Frédéric M. Vaz, E. M. Kemper, Bwee Tien Poll-The, Marc Engelen, Bart G. P. Koot, Sacha Ferdinandusse, Kevin Berendse, Peter L.M. Jansen, Hans R. Waterham, Ronald J.A. Wanders |
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| Přispěvatelé: | Other departments, Laboratory Genetic Metabolic Diseases, Paediatric Gastroenterology, Pharmacy, Paediatric Metabolic Diseases, ANS - Cellular & Molecular Mechanisms, Paediatric Neurology, Neurology, Promovendi NTM, RS: NUTRIM - R2 - Gut-liver homeostasis, Surgery |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent Bilirubin medicine.drug_class Zellweger Spectrum Cholic Acid Biology Bile Acids and Salts 03 medical and health sciences chemistry.chemical_compound Young Adult 0302 clinical medicine Internal medicine medicine Genetics Humans Genetics(clinical) Longitudinal Studies Child Zellweger Syndrome Genetics (clinical) Transaminases Zellweger syndrome Bile acid Liver Diseases Cholic acid Peroxisome medicine.disease PHEX Phosphate Regulating Neutral Endopeptidase 030104 developmental biology Endocrinology chemistry Liver Child Preschool 030211 gastroenterology & hepatology Female Original Article Liver function Liver dysfunction |
| Zdroj: | Journal of Inherited Metabolic Disease Journal of inherited metabolic disease, 39(6), 859-868. Springer Netherlands Journal of Inherited Metabolic Disease, 39(6), 859-868. Wiley |
| ISSN: | 1573-2665 0141-8955 |
| Popis: | Introduction Zellweger spectrum disorders (ZSDs) are characterized by a failure in peroxisome formation, caused by autosomal recessive mutations in different PEX genes. At least some of the progressive and irreversible clinical abnormalities in patients with a ZSD, particularly liver dysfunction, are likely caused by the accumulation of toxic bile acid intermediates. We investigated whether cholic acid supplementation can suppress bile acid synthesis, reduce accumulation of toxic bile acid intermediates and improve liver function in these patients. Methods An open label, pretest-posttest design study was conducted including 19 patients with a ZSD. Participants were followed longitudinally during a period of 2.5 years prior to the start of the intervention. Subsequently, all patients received oral cholic acid and were followed during 9 months of treatment. Bile acids, peroxisomal metabolites, liver function and liver stiffness were measured at baseline and 4, 12 and 36 weeks after start of cholic acid treatment. Results During cholic acid treatment, bile acid synthesis decreased in the majority of patients. Reduced levels of bile acid intermediates were found in plasma and excretion of bile acid intermediates in urine was diminished. In patients with advanced liver disease (n = 4), cholic acid treatment resulted in increased levels of plasma transaminases, bilirubin and cholic acid with only a minor reduction in bile acid intermediates. Conclusions Oral cholic acid therapy can be used in the majority of patients with a ZSD, leading to at least partial suppression of bile acid synthesis. However, caution is needed in patients with advanced liver disease due to possible hepatotoxic effects. Electronic supplementary material The online version of this article (doi:10.1007/s10545-016-9962-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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