Abstract
In this case series, we demonstrate that Ursodeoxycholic acid (UDCA) improves liver dysfunction in Niemann-Pick type C (NPC) and may restore a suppressed cytochrome p450 system. NPC disease is a progressive neurodegenerative lysosomal storage disease caused by mutations in either the NPC1 or NPC2 genes. Liver disease is a common feature presenting either acutely as cholestatic jaundice in the neonatal period, or in later life as elevated liver enzymes indicative of liver dysfunction. Recently, an imbalance in bile acid synthesis in a mouse model of NPC disease was linked to suppression of the P450 detoxification system and was corrected by UDCA treatment. UDCA (3α, 7β-dihydroxy-5β-cholanic acid), a hydrophilic bile acid, is used to treat various cholestatic disorders. In this report we summarise the findings from four independent cases of NPC, three with abnormal liver enzyme levels at baseline, that were subsequently treated with UDCA. The patients differed in age and clinical features, they all tolerated the drug well, and in those with abnormal liver function, there were significant improvements in their liver enzyme parameters.
Funder
Wellcome Trust
Niemann-Pick Research Foundation
Action Medical Research
Brian and Caris Chan Family Foundation
Royal Society
Subject
General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference27 articles.
1. Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update.;M Patterson;Mol Genet Metab.,2012
2. Observational, retrospective study of a large cohort of patients with Niemann-Pick disease type C in the Czech Republic: a surprisingly stable diagnostic rate spanning almost 40 years.;H Jahnova;Orphanet J Rare Dis.,2014
3. High incidence of unrecognized visceral/neurological late-onset Niemann-Pick disease, type C1, predicted by analysis of massively parallel sequencing data sets.;C Wassif;Genet Med.,2016
4. Linear clinical progression, independent of age of onset, in Niemann-Pick disease, type C.;N Yanjanin;Am J Med Genet B Neuropsychiatr Genet.,2010
5. Lipids on trial: the search for the offending metabolite in Niemann-Pick type C disease.;E Lloyd-Evans;Traffic.,2010
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