Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/17333
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Prediction of neuropathology in mucopolysaccharidosis I patients |
Author: | Fuller, M. Brooks, D. Evangelista, M. Hein, L. Hopwood, J. Meikle, P. |
Citation: | Molecular Genetics and Metabolism, 2005; 84(1):18-24 |
Publisher: | Academic Press Inc Elsevier Science |
Issue Date: | 2005 |
ISSN: | 1096-7192 1096-7206 |
Abstract: | Mucopolysaccharidosis I is a lysosomal storage disorder caused by a deficiency of the lysosomal hydrolase alpha-l-iduronidase, which is required for the degradation of heparan sulphate and dermatan sulphate. Given the wide spectrum of disease severity in mucopolysaccharidosis I patients, one of the challenges for managing the disorder is to accurately predict clinical phenotype. Enzyme replacement therapy by intravenous infusion is unlikely to make a significant impact on central nervous system pathology and patients displaying this clinical manifestation may respond better to bone marrow transplantation. In order to predict whether mucopolysaccharidosis I patients are going to develop central nervous system pathology, we investigated a number of biochemical parameters in cultured skin fibroblasts from patients of different genotype/phenotype. Residual levels of alpha-l-iduronidase activity and protein were determined using sensitive immune-quantification assays and fibroblast cell extracts from patients with central nervous system pathology generally had lower levels of alpha-l-iduronidase than patients with no evidence of central nervous system disease. A total of 15 oligosaccharides, derived from heparan sulphate and dermatan sulphate, was measured in fibroblast extracts using electrospray-ionisation tandem mass spectrometry and all were shown to discriminate mucopolysaccharidosis I from controls. Of these, two trisaccharides were able to group patients based on the presence/absence of central nervous system disease. Moreover, a ratio of alpha-l-iduronidase activity to these trisaccharides provided clear discrimination between mucopolysaccharidosis I patients with and without central nervous system pathology. We suggest that this type of analysis may be very useful for predicting disease severity in mucopolysaccharidosis I patients. |
Keywords: | Central Nervous System Cells, Cultured Fibroblasts Skin Humans Mucopolysaccharidosis I Iduronidase Dermatan Sulfate Heparitin Sulfate Oligosaccharides Genotype Phenotype Forecasting Adolescent Adult Child Child, Preschool Infant Mass Spectrometry |
DOI: | 10.1016/j.ymgme.2004.09.004 |
Published version: | http://dx.doi.org/10.1016/j.ymgme.2004.09.004 |
Appears in Collections: | Aurora harvest 2 Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.