Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/7714
Citations | ||
Scopus | Web of ScienceĀ® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Prediction of Sanfilippo phenotype severity from immunoquantification of heparan-N-sulfamidase in cultured fibroblasts from mucopolysaccharidosis type IIIA patients |
Author: | Perkins, K. Muller, V. Weber, B. Hopwood, J. |
Citation: | Molecular Genetics and Metabolism, 2001; 73(4):306-312 |
Publisher: | Academic Press Inc |
Issue Date: | 2001 |
ISSN: | 1096-7192 1096-7206 |
Statement of Responsibility: | Perkins, Kelly J. ; Muller, Vivienne ; Weber, Birgit ; Hopwood, John J. |
Abstract: | Mucopolysaccharidosis type IIIA (MPS-IIIA) is an autosomal recessive lysosomal storage disorder caused by the deficiency of heparan-N-sulfamidase (NS; EC 3.10.1.1), resulting in defective degradation and subsequent storage of heparan sulfate and leading to a clinical phenotype known as Sanfilippo syndrome. A sensitive and specific monoclonal/polyclonal-based immunoquantification assay has enabled the determination of NS protein, down to approximately 3 pg NS protein, in cultured fibroblasts from control and MPS-IIIA patients. Cultured skin fibroblasts from 15 normal controls contained 11.9 to 105 ng of NS protein/mg extracted cell protein, whereas NS protein ranged from "none detected" to 11 ng/mg in fibroblasts from 35 MPS-IIIA patients. A relationship between genotype/phenotype and amount of NS protein present in these MPS-IIIA fibroblasts was established. Immunoquantification, in combination with a specific and highly sensitive tetrasaccharide-based assay of NS activity, enabled the determination of residual specific NS activity in these fibroblasts. Specific NS activity ranged from 28 to 1289 nmol/min/mg NS protein for MPS-IIIA patients, compared to 870 nmol/min/mg of recombinant human NS. It is proposed that this immunoquantification method, in conjunction with the specific NS activity assay, may be used to predict clinical severity in MPS-IIIA patients, allowing for the selection of individuals best suited for gene- and enzyme-replacement therapy when these methods become available. Also proposed is that an enzyme-replacement therapy achieving a correction of approximately 10% of normal NS activity is required to avoid the onset of a Sanfilippo clinical phenotype. |
Keywords: | Cells, Cultured Fibroblasts Humans Mucopolysaccharidosis III Hydrolases Enzyme-Linked Immunosorbent Assay Enzyme Stability Phenotype Mutation Reference Standards Adolescent Adult Child, Preschool Infant |
DOI: | 10.1006/mgme.2001.3190 |
Published version: | http://dx.doi.org/10.1006/mgme.2001.3190 |
Appears in Collections: | Aurora harvest 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.