title: Validation of keratan sulfate level in mucopolysaccharidosis type IVA by liquid chromatography-tandem mass spectrometry.
abstract: 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.
authors.affiliation: Department of Pediatrics, Saint Louis University Doisy Research Center, 1100 South Grand Blvd, St Louis, MO 63104, USA. tomatsus@slu.edu
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Oguma
authors.forename: Vu Chi
authors.initials: VC
authors.lastname: Dung
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Oikawa
authors.forename: Talita Giacomet
authors.initials: TG
authors.lastname: de Carvalho
authors.forename: María L
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masaru
authors.initials: M
authors.lastname: Fukushi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kida
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kubota
authors.forename: Luis
authors.initials: L
authors.lastname: Barrera
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D042241:Early Diagnosis; D006801:Humans; D007223:Infant; D007632:Keratan Sulfate / Q000097:blood*; D008875:Middle Aged; D009085:Mucopolysaccharidosis IV / Q000097:blood* / Q000175:diagnosis*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007632:Keratan Sulfate