BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an inherited lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme required for stepwise degradation of keratan sulfate (KS). We have developed a selective, sensitive, accurate and precise LC-MS/MS assay for the KS-derived disaccharides Galβ1-4GlcNAc(6S) and Gal(6S)β1-4GlcNAc(6S) in human urine and plasma using keratanase II digestion. RESULTS: Mean accuracy was 96-106% in urine and 97-108% in plasma. Precision was high, with relative standard deviations of 1-2% (intra-day) and 2-5% (inter-day) in urine and 1-2% (intra-day) and 4-7% (inter-day) in plasma. The lower limit of quantitation was 0.026 µg/ml (plasma) and 0.104 µg/ml (urine), with a quantitation range of 0.026-5 µg/ml (plasma) and 0.104-20 µg/ml (urine). CONCLUSION: Clinical sample analysis in 168 MPS IVA patients and 225 healthy controls demonstrates the clinical utility of this method.
BACKGROUND:Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an inherited lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS), an enzyme required for stepwise degradation of keratan sulfate (KS). We have developed a selective, sensitive, accurate and precise LC-MS/MS assay for the KS-derived disaccharidesGalβ1-4GlcNAc(6S) and Gal(6S)β1-4GlcNAc(6S) in human urine and plasma using keratanase II digestion. RESULTS: Mean accuracy was 96-106% in urine and 97-108% in plasma. Precision was high, with relative standard deviations of 1-2% (intra-day) and 2-5% (inter-day) in urine and 1-2% (intra-day) and 4-7% (inter-day) in plasma. The lower limit of quantitation was 0.026 µg/ml (plasma) and 0.104 µg/ml (urine), with a quantitation range of 0.026-5 µg/ml (plasma) and 0.104-20 µg/ml (urine). CONCLUSION: Clinical sample analysis in 168 MPS IVApatients and 225 healthy controls demonstrates the clinical utility of this method.
Authors: Shaukat Khan; Carlos J Alméciga-Díaz; Kazuki Sawamoto; William G Mackenzie; Mary C Theroux; Christian Pizarro; Robert W Mason; Tadao Orii; Shunji Tomatsu Journal: Mol Genet Metab Date: 2016-11-29 Impact factor: 4.797
Authors: Shunji Tomatsu; Eriko Yasuda; Pravin Patel; Kristen Ruhnke; Tsutomu Shimada; William G Mackenzie; Robert Mason; Mihir M Thacker; Mary Theroux; Adriana M Montaño; Carlos J Alméciga-Díaz; Luis A Barrera; Yasutsugu Chinen; William S Sly; Daniel Rowan; Yasuyuki Suzuki; Tado Orii Journal: Pediatr Endocrinol Rev Date: 2014-09
Authors: Roger Lawrence; Jillian R Brown; Fred Lorey; Patricia I Dickson; Brett E Crawford; Jeffrey D Esko Journal: Mol Genet Metab Date: 2013-07-29 Impact factor: 4.797
Authors: A Morrone; K L Tylee; M Al-Sayed; A C Brusius-Facchin; A Caciotti; H J Church; M J Coll; K Davidson; M J Fietz; L Gort; M Hegde; F Kubaski; L Lacerda; F Laranjeira; S Leistner-Segal; S Mooney; S Pajares; L Pollard; I Ribeiro; R Y Wang; N Miller Journal: Mol Genet Metab Date: 2014-03-20 Impact factor: 4.797