Journal of Inherited Metabolic Disease

, Volume 33, Issue 2, pp 141–150

Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I

  • Shunji Tomatsu
  • Adriana M. Montaño
  • Toshihiro Oguma
  • Vu Chi Dung
  • Hirotaka Oikawa
  • Talita Giacomet de Carvalho
  • María L. Gutiérrez
  • Seiji Yamaguchi
  • Yasuyuki Suzuki
  • Masaru Fukushi
  • Nobuo Sakura
  • Luis Barrera
  • Kazuhiro Kida
  • Mitsuru Kubota
  • Tadao Orii
Original Article

DOI: 10.1007/s10545-009-9036-3

Cite this article as:
Tomatsu, S., Montaño, A.M., Oguma, T. et al. J Inherit Metab Dis (2010) 33: 141. doi:10.1007/s10545-009-9036-3

Abstract

Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by deficiency of α-L-iduronidase leading to accumulation of its catabolic substrates, dermatan sulfate (DS) and heparan sulfate (HS), in lysosomes. This results in progressive multiorgan dysfunction and death in early childhood. The recent success of enzyme replacement therapy (ERT) for MPS I highlights the need for biomarkers that reflect response to such therapy. To determine which biochemical markers are better, we determined serum and urine DS and HS levels by liquid chromatography tandem mass spectrometry in ERT-treated MPS I patients. The group included one Hurler, 11 Hurler/Scheie, and two Scheie patients. Seven patients were treated from week 1, whereas the other seven were treated from week 26. Serum and urine DS (ΔDi-4S/6S) and HS (ΔDiHS-0S, ΔDiHS-NS) were measured at baseline, week 26, and week 72. Serum ΔDi-4S/6S, ΔDiHS-0S, and ΔDiHS-NS levels decreased by 72%, 56%, and 56%, respectively, from baseline at week 72. Urinary glycosaminoglycan level decreased by 61.2%, whereas urine ΔDi-4S/6S, ΔDiHS-0S, and ΔDiHS-NS decreased by 66.8%, 71.8%, and 71%, respectively. Regardless of age and clinical severity, all patients showed marked decrease of DS and HS in blood and urine samples. We also evaluated serum DS and HS from dried blood-spot samples of three MPS I newborn patients, showing marked elevation of DS and HS levels compared with those in control newborns. In conclusion, blood and urine levels of DS and HS provide an intrinsic monitoring and screening tool for MPS I patients.

Abbreviations

DS

Dermatan sulfate

HS

Heparan sulfate

LSD

Lysosomal storage disease

MPS

Mucopolysaccharidoses

GAG

Glycosaminoglycan

DMB

Dimethylmethylene blue

∆DiHS

Unsaturated disaccharide unit from heparan sulfate

∆DiHS-0S (∆HexUAα1–4GlcNAc)

2-acetamido-2-deoxy-4-O-(4-deoxy-a-L-threo-hex-4-enopyranosyluronic acid) -D-glucose

∆DiHS-NS [∆HexUAα1-4GlcN(2-N-sulfate)]

2-deoxy-2-sulfamino-4-O-(4-deoxy-a-L-threo-hex-4-enopyranosyluronic acid)-D-glucose

∆Di-4S/6S [∆HexUAα1–4GlcNAc(4/6-O-sulfate)]

2-acetamido-2-deoxy-4-O-(4-deoxy-a-L-threohex-4-enopyranosyluronic acid)-4/6-O-sulfo-D-glucose

HPLC

High-performance liquid chromatography

LC/MS/MS

Liquid chromatography tandem mass spectrometry

NBS

Newborn screening

HCII-T

Complex heparin cofactor II–thrombin

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Shunji Tomatsu
    • 1
    • 9
  • Adriana M. Montaño
    • 1
  • Toshihiro Oguma
    • 2
  • Vu Chi Dung
    • 1
  • Hirotaka Oikawa
    • 1
  • Talita Giacomet de Carvalho
    • 1
  • María L. Gutiérrez
    • 1
  • Seiji Yamaguchi
    • 3
  • Yasuyuki Suzuki
    • 4
  • Masaru Fukushi
    • 5
  • Nobuo Sakura
    • 6
  • Luis Barrera
    • 7
  • Kazuhiro Kida
    • 8
  • Mitsuru Kubota
    • 8
  • Tadao Orii
    • 4
  1. 1.Department of PediatricsSaint Louis UniversitySt. LouisUSA
  2. 2.Daiichi-Sankyo Co., LtdTokyoJapan
  3. 3.Department of PediatricsShimane UniversityShimaneJapan
  4. 4.Department of PediatricsGifu UniversityGifuJapan
  5. 5.Sapporo City Institute of Public HealthSapporoJapan
  6. 6.Suzugamine HospitalHiroshimaJapan
  7. 7.Instituto de Errores Innatos del MetabolismoPontificia Universidad JaverianaBogotaColombia
  8. 8.Department of PediatricsHokkaido UniversitySapporoJapan
  9. 9.Department of PediatricsSaint Louis University Doisy Research CenterSt. LouisUSA

Personalised recommendations