title: Development and testing of new screening method for keratan sulfate in mucopolysaccharidosis IVA.
abstract: Mucopolysaccharidosis IVA (MPS IVA), a progressive lysosomal storage disease, causes skeletal dysplasia through excessive storage of keratan sulfate (KS). We developed an ELISA-sandwich assay that used a MAb specific to KS. Forty-five blood and 59 urine specimens from MPS IVA patients (ages 1-65 y) were analyzed to determine whether KS concentration is a suitable marker for early diagnosis and longitudinal assessment of disease severity. Blood specimens were obtained from patients categorized as phenotypically severe (n = 36) and milder (n = 9). Urine specimens were also analyzed from patients categorized as severe (n = 56) and milder (n = 12), respectively. Blood KS levels (101-1525 ng/mL) in MPS IVA patients were two to eight times higher than those in age-matched controls (15-323 ng/mL). It was found that blood KS level varied with age and clinical severity. Blood KS levels in both MPS IVA and controls peaked between 5 and 10 y of age (mean, 776 versus 234 ng/mL, respectively). Blood levels in severe MPS IVA were 1.5 times higher than in the milder form. In contrast to blood, urine KS levels in both MPS IVA and controls peaked between 1 and 5 y (15.3 versus 0.26 mg/g creatinine), and thereafter declined with age. Urine KS level also varied with age and clinical severity, and the severe MPS IVA phenotype was associated with 6.7 times greater urine KS excretion than the milder one. These findings indicate that the new assay for blood or urine KS may be suitable for early diagnosis and longitudinal assessment of disease severity in MPS IVA.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. tomatsus@slu.edu
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Koji O
authors.initials: KO
authors.lastname: Orii
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nishioka
authors.forename: Monica A
authors.initials: MA
authors.lastname: Gutierrez
authors.forename: Susana
authors.initials: S
authors.lastname: Velez-Castrillon
authors.forename: Abgela A
authors.initials: AA
authors.lastname: Fachel
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Grubb
authors.forename: Alan
authors.initials: A
authors.lastname: Cooper
authors.forename: Margaret
authors.initials: M
authors.lastname: Thornley
authors.forename: Ed
authors.initials: E
authors.lastname: Wraith
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ida V
authors.initials: IV
authors.lastname: Schwartz
authors.forename: Gudrun Schulze
authors.initials: GS
authors.lastname: Frenking
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Kircher
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Kurt
authors.initials: K
authors.lastname: Ullrich
authors.forename: Koji
authors.initials: K
authors.lastname: Isogai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.forename: Michael
authors.initials: M
authors.lastname: Creer
authors.forename: Akihiko
authors.initials: A
authors.lastname: Noguchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005820:Genetic Testing / Q000379:methods*; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007223:Infant; D007632:Keratan Sulfate / Q000097:blood* / Q000652:urine*; D008875:Middle Aged; D009085:Mucopolysaccharidosis IV / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology / Q000652:urine*; D015203:Reproducibility of Results; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D007632:Keratan Sulfate