TY - JOUR
T1 - N-Acetylgalactosamine-6-sulfatase protein detection in MPS IVA patient and unaffected control samples
AU - Parkinson-Lawrence, Emma J.
AU - Muller, Viv J.
AU - Hopwood, John J.
AU - Brooks, Doug A.
N1 - Funding Information:
This study was supported by National Health and Medical Research Council of Australia Fellowship and Program Grant funding. The authors thank Shire Human Genetic Therapies for the kind gift of monoclonal antibodies and purified recombinant GALNS protein, Chris Boulter for assistance with tissue culture and Debbie Lang for europium labelling the monoclonal antibody.
PY - 2007/2/2
Y1 - 2007/2/2
N2 - Background: Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome) is a lysosomal storage disorder caused by a deficiency in the activity of the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS). MPS IVA patients can present with severe myelopathy, hearing loss, heart valve involvement, short trunk/dwarfism and corneal clouding. Early diagnosis of MPS IVA will allow potential treatments to be implemented before the onset of irreversible pathology. Methods: We have developed a sensitive immune-quantification assay for the accurate detection of GALNS protein in skin fibroblasts, blood and plasma from unaffected control and MPS IVA patients. Results: MPS IVA patient fibroblast extracts (n = 11) had non-detectable (ND)-10 ng/mg of 6-sulfatase protein compared to 3-82 ng/mg for normal controls (n = 19). Dried blood-spots from MPS IVA patients (n = 4) contained ND-1.3 ng/L of 6-sulfatase protein compared to 18-145 ng/L for normal controls (n = 49). Plasma from MPS IVA patients (n = 7) contained ND 6-sulfatase protein compared to 1-9 ng/L for normal controls (n = 49). Conclusions: The immune assay described here had the capacity to accurately measure the amount of GALNS protein in various biological samples, providing the basis of an assay that could be further developed to enable newborn and high-risk population screening for MPS IVA patients.
AB - Background: Mucopolysaccharidosis type IVA (MPS IVA; Morquio syndrome) is a lysosomal storage disorder caused by a deficiency in the activity of the lysosomal hydrolase N-acetylgalactosamine-6-sulfatase (GALNS). MPS IVA patients can present with severe myelopathy, hearing loss, heart valve involvement, short trunk/dwarfism and corneal clouding. Early diagnosis of MPS IVA will allow potential treatments to be implemented before the onset of irreversible pathology. Methods: We have developed a sensitive immune-quantification assay for the accurate detection of GALNS protein in skin fibroblasts, blood and plasma from unaffected control and MPS IVA patients. Results: MPS IVA patient fibroblast extracts (n = 11) had non-detectable (ND)-10 ng/mg of 6-sulfatase protein compared to 3-82 ng/mg for normal controls (n = 19). Dried blood-spots from MPS IVA patients (n = 4) contained ND-1.3 ng/L of 6-sulfatase protein compared to 18-145 ng/L for normal controls (n = 49). Plasma from MPS IVA patients (n = 7) contained ND 6-sulfatase protein compared to 1-9 ng/L for normal controls (n = 49). Conclusions: The immune assay described here had the capacity to accurately measure the amount of GALNS protein in various biological samples, providing the basis of an assay that could be further developed to enable newborn and high-risk population screening for MPS IVA patients.
KW - Immune-quantification
KW - Lysosomal storage disorder
KW - Morquio syndrome
KW - Mucopolysaccharidosis type IVA
KW - N-Acetylgalactosamine-6-sulfatase
KW - Variant protein
UR - http://www.scopus.com/inward/record.url?scp=33845468343&partnerID=8YFLogxK
U2 - 10.1016/j.cca.2006.08.030
DO - 10.1016/j.cca.2006.08.030
M3 - Article
C2 - 17027703
AN - SCOPUS:33845468343
SN - 0009-8981
VL - 377
SP - 88
EP - 91
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
IS - 1-2
ER -