TY - JOUR
T1 - Determination of monosaccharides and disaccharides in mucopolysaccharidoses patients by electrospray ionisation mass spectrometry
AU - Ramsay, Steven L.
AU - Meikle, Peter J.
AU - Hopwood, John J.
N1 - Funding Information:
We are grateful to the MPS patients and their families for the use of their urine and blood samples used in this study. Staff members also kindly donated control urine and blood. Pharming BV (The Netherlands), TLH Research (USA) and the National Health and Medical Research Council (Australia) are gratefully acknowledged for their financial support.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - The mucopolysaccharidoses are a group of lysosomal storage disorders characterised by the storage of glycosaminoglycans. With the exception of Hunters syndrome (MPS II), which is X-linked, they are autosomal recessively inherited resulting in a defect in any one of 10 lysosomal enzymes needed to catabolise glycosaminoglycans. The type and size of the glycosaminoglycans stored in lysosomes are determined by the particular enzyme deficiency. These glycosaminoglycan elevations are subsequently observed in tissue, circulation, and urine. A method has been developed for the derivatisation and quantification of sulfated N-acetylhexosamine-containing mono- and disaccharides from patient samples by electrospray ionisation tandem mass spectrometry. Urine from most mucopolysaccharidoses types had significant increases in di- and monosulfated N-acetylhexosamines (GalNAc4,6S, GalNAc6S, GalNAc4S, or GlcNAc6S) and monosulfated N-acetylhexosamine-uronic acid disaccharides (GalNAc6S-UA, GalNAc4S-UA, or GlcNAc6S-UA). Analysis of plasma and dried blood spots on filter paper collected from mucopolysaccharidoses patients showed elevations of total monosulfated N-acetylhexosamines but less than that seen in urine. Urine samples from bone marrow transplant recipients, mucopolysaccharidosis IVA and mucopolysaccharidosis VI patients, showed decreases in HexNAcS, HexNAcS2/GalNAc4,6S, and HexNAcS-UA post-transplant. This decrease correlated with clinical improvement to levels comparable with those identified in patients with less severe phenotypes. These metabolic markers therefore have potential applications in diagnosis, phenotype prediction and monitoring of current and future therapies, particularly for the mucopolysaccharidosis IIID, IVA, VI, and multiple sulfatase deficiency. This paper reports a sensitive and simple method for the measurement of sulfated N-acetylhexosamines and sulfated disaccharides shown to be elevated in some mucopolysaccharidosis and multiple sulfatase deficient patients.
AB - The mucopolysaccharidoses are a group of lysosomal storage disorders characterised by the storage of glycosaminoglycans. With the exception of Hunters syndrome (MPS II), which is X-linked, they are autosomal recessively inherited resulting in a defect in any one of 10 lysosomal enzymes needed to catabolise glycosaminoglycans. The type and size of the glycosaminoglycans stored in lysosomes are determined by the particular enzyme deficiency. These glycosaminoglycan elevations are subsequently observed in tissue, circulation, and urine. A method has been developed for the derivatisation and quantification of sulfated N-acetylhexosamine-containing mono- and disaccharides from patient samples by electrospray ionisation tandem mass spectrometry. Urine from most mucopolysaccharidoses types had significant increases in di- and monosulfated N-acetylhexosamines (GalNAc4,6S, GalNAc6S, GalNAc4S, or GlcNAc6S) and monosulfated N-acetylhexosamine-uronic acid disaccharides (GalNAc6S-UA, GalNAc4S-UA, or GlcNAc6S-UA). Analysis of plasma and dried blood spots on filter paper collected from mucopolysaccharidoses patients showed elevations of total monosulfated N-acetylhexosamines but less than that seen in urine. Urine samples from bone marrow transplant recipients, mucopolysaccharidosis IVA and mucopolysaccharidosis VI patients, showed decreases in HexNAcS, HexNAcS2/GalNAc4,6S, and HexNAcS-UA post-transplant. This decrease correlated with clinical improvement to levels comparable with those identified in patients with less severe phenotypes. These metabolic markers therefore have potential applications in diagnosis, phenotype prediction and monitoring of current and future therapies, particularly for the mucopolysaccharidosis IIID, IVA, VI, and multiple sulfatase deficiency. This paper reports a sensitive and simple method for the measurement of sulfated N-acetylhexosamines and sulfated disaccharides shown to be elevated in some mucopolysaccharidosis and multiple sulfatase deficient patients.
KW - 1-Phenyl-3-methyl pyrazolone (PMP)
KW - Electrospray mass spectrometry (ESI-MS)
KW - Glycosaminoglycans (GAGs)
KW - Mucopolysaccharidoses (MPS)
UR - http://www.scopus.com/inward/record.url?scp=0037342766&partnerID=8YFLogxK
U2 - 10.1016/S1096-7192(03)00018-0
DO - 10.1016/S1096-7192(03)00018-0
M3 - Article
C2 - 12649064
AN - SCOPUS:0037342766
SN - 1096-7192
VL - 78
SP - 193
EP - 204
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 3
ER -