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Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography–tandem mass spectrometry
Author(s) -
Tomatsu Shunji,
Montaño Adriana M.,
Oguma Toshihiro,
Dung Vu Chi,
Oikawa Hirotaka,
Carvalho Talita Giacomet,
Gutiérrez María L.,
Yamaguchi Seiji,
Suzuki Yasuyuki,
Fukushi Masaru,
Kida Kazuhiro,
Kubota Mitsuru,
Barrera Luis,
Orii Tadao
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-009-9013-x
Subject(s) - keratan sulfate , mucopolysaccharidosis , tandem mass spectrometry , medicine , biomarker , liquid chromatography–mass spectrometry , endocrinology , gastroenterology , chemistry , chromatography , mass spectrometry , glycosaminoglycan , chondroitin sulfate , biochemistry
Mucopolysaccharidosis type IVA (MPS IVA, Morquio A disease), a progressive lysosomal storage disease, causes skeletal chondrodysplasia through excessive storage of keratan sulfate (KS). KS is synthesized mainly in cartilage and released to the circulation. The excess storage of KS disrupts cartilage, consequently releasing more KS into circulation, which is a critical biomarker for MPS IVA. Thus, assessment of KS level provides a potential screening strategy and determines clinical course and efficacy of therapies. We have recently developed a tandem mass spectrometry liquid chromatography [LC/MS/MS] method to assay KS levels in blood. Forty‐nine blood specimens from patients with MPS IVA [severe ( n = 33), attenuated ( n = 11) and undefined ( n = 5)] were analyzed for comparison of blood KS concentration with that of healthy subjects and for correlation with clinical severity. Plasma samples were digested by keratanase II to obtain disaccharides of KS. Digested samples were assayed by LC/MS/MS. We found that blood KS levels (0.4–26 µg/ml) in MPS IVA patients were significantly higher than those in age‐matched controls (0.67–4.6 µg/ml; P < 0.0001). It was found that blood KS level varied with age and clinical severity in the patients. Blood KS levels in MPS IVA peaked between 2 years and 5 years of age (mean 11.4 µg/ml). Blood KS levels in severe MPS IVA (mean 7.3 µg/ml) were higher than in the attenuated form (mean 2.1 µg/ml) ( P = 0.012). We also found elevated blood KS levels in other types of MPS. These findings indicate that the new KS assay for blood is suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.