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Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders

Zellweger spectrum disorders (ZSDs), a subgroup of peroxisomal biogenesis disorders, have a generalized defect in peroxisome function. Liver disease in ZSDs has been linked to accumulation of C(27)-bile acid intermediates due to the lack of peroxisomal β-oxidation of these intermediates to form prim...

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Autores principales: Heubi, James E., Setchell, Kenneth D.R., Bove, Kevin E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062720/
https://www.ncbi.nlm.nih.gov/pubmed/30057520
http://dx.doi.org/10.1159/000490095
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author Heubi, James E.
Setchell, Kenneth D.R.
Bove, Kevin E.
author_facet Heubi, James E.
Setchell, Kenneth D.R.
Bove, Kevin E.
author_sort Heubi, James E.
collection PubMed
description Zellweger spectrum disorders (ZSDs), a subgroup of peroxisomal biogenesis disorders, have a generalized defect in peroxisome function. Liver disease in ZSDs has been linked to accumulation of C(27)-bile acid intermediates due to the lack of peroxisomal β-oxidation of these intermediates to form primary C(24)-bile acids. Oral treatment with primary bile acid, cholic acid (CA), inhibits formation of hepatotoxic C(27)-bile acids by restoring normal physiologic feedback inhibition on bile acid synthesis. We present the long-term CA treatment and liver-related outcomes for 3 pediatric patients with ZSDs who have received CA treatment for ≥15 years. Ongoing CA treatment was associated with stabilized liver function, as shown by serum biochemistries and liver histopathology, and no treatment-related adverse effects were observed. All 3 patients have attended regular school with classroom accommodations and attained a good quality of life. Our patient outcomes suggest that early and ongoing CA therapy may sustain liver function in patients with ZSDs.
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spelling pubmed-60627202018-07-27 Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders Heubi, James E. Setchell, Kenneth D.R. Bove, Kevin E. Case Rep Gastroenterol Case Series Zellweger spectrum disorders (ZSDs), a subgroup of peroxisomal biogenesis disorders, have a generalized defect in peroxisome function. Liver disease in ZSDs has been linked to accumulation of C(27)-bile acid intermediates due to the lack of peroxisomal β-oxidation of these intermediates to form primary C(24)-bile acids. Oral treatment with primary bile acid, cholic acid (CA), inhibits formation of hepatotoxic C(27)-bile acids by restoring normal physiologic feedback inhibition on bile acid synthesis. We present the long-term CA treatment and liver-related outcomes for 3 pediatric patients with ZSDs who have received CA treatment for ≥15 years. Ongoing CA treatment was associated with stabilized liver function, as shown by serum biochemistries and liver histopathology, and no treatment-related adverse effects were observed. All 3 patients have attended regular school with classroom accommodations and attained a good quality of life. Our patient outcomes suggest that early and ongoing CA therapy may sustain liver function in patients with ZSDs. S. Karger AG 2018-06-28 /pmc/articles/PMC6062720/ /pubmed/30057520 http://dx.doi.org/10.1159/000490095 Text en Copyright © 2018 by S. Karger AG, Basel http://creativecommons.org/licenses/by-nc/4.0/ This article is licensed under the Creative Commons Attribution-NonCommercial-4.0 International License (CC BY-NC) (http://www.karger.com/Services/OpenAccessLicense). Usage and distribution for commercial purposes requires written permission.
spellingShingle Case Series
Heubi, James E.
Setchell, Kenneth D.R.
Bove, Kevin E.
Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title_full Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title_fullStr Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title_full_unstemmed Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title_short Long-Term Cholic Acid Therapy in Zellweger Spectrum Disorders
title_sort long-term cholic acid therapy in zellweger spectrum disorders
topic Case Series
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062720/
https://www.ncbi.nlm.nih.gov/pubmed/30057520
http://dx.doi.org/10.1159/000490095
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