• Title/Summary/Keyword: Mucopolysaccharidosis

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Mucopolysaccharidosis Type III: review and recent therapies under investigation

  • Lee, Jun Hwa
    • Journal of Interdisciplinary Genomics
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    • v.2 no.2
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    • pp.20-25
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    • 2020

  • Mucopolysaccharidosis type III (MPS III or Sanfilippo syndrome) is a multisystem lysosomal storage disease that is inherited in an autosomal recessive manner. It consists of four subtypes (MPS IIIA, B, C, and D), each characterized by the deficiency of different enzymes that catalyze the metabolism of the glycosaminoglycan heparan sulfate at the lysosomal level. The typical clinical manifestation of MPS III includes progressive central nervous system (CNS) degeneration with accompanying systemic manifestations. Disease onset is typically before the age of ten years and death usually occurs in the second or third decade due to neurological regression or respiratory tract infections. However, there is currently no treatment for CNS symptoms in patients with MPS III. Invasive and non-invasive techniques that allow drugs to pass through the blood brain barrier and reach the CNS are being tested and have proven effective. In addition, the application of genistein treatment as a substrate reduction therapy is in progress.

  • https://doi.org/10.22742/JIG.2020.2.2.20 인용 PDF KSCI

Keratanase II Digestion Accompanied with a Liquid Chromatography/Tandem Mass Spectrometry for Urinary Keratan Sulfate Quantitative Analysis

  • Chuang, Chih-Kuang;Lin, Hsiang-Yu;Wang, Tuen-Jen;Huang, Sung-Fa;Lin, Shuan-Pei
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.3 no.1
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    • pp.20-27
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    • 2017

  • Purpose: Mucopolysaccharidosis IV (MPS IV) is a disease characterized by deficient activity of N-acetylgalactosamine-6-sulfatase (GALNS) causing excessive lysosomal storage of keratan sulfate (KS). The identification of the relevant disaccharide units of KS after keratanase II digestion followed by liquid chromatography/tandem mass spectrometry detection (LC-MS/MS) is validated and applicable for the preliminary diagnosis of MPS IV. Methods: A total of 67 urine samples were collected and analyzed from 11 MPS IV patients comprising 10 MPS IVA and one MPS IVB patients, and 56 normal controls. Urinary glycosaminoglycan was first precipitated by the Alcian blue method followed by a digestion of keratanase II. The protonated species of the digested disaccharide products were detected by using multiple reaction monitoring experiment. Results: One particular disaccharide of KS was selected. The transition mass-to-charge (m/z) of the parent ion and its daughter ion after collision was $462.0{\rightarrow}97.0$, whereas the chondrosine used as an internal standard in this assay was m/z $353.9{\rightarrow}73.0$. The results corresponded well with the two-dimensional electrophoresis method. The quantities of urinary KS were significantly raised in confirmed MPS IV patients when comparing with those of normal controls ($170.2{\pm}81.1$ vs. $4.06{\pm}1.92{\mu}g/mL$). Conclusion: The LC-MS/MS method for MPS IVA determination is specific, sensitive, validated, and applicable for urinary KS quantification. This method can be used not only as a first-line biochemistry examination of MPS IVA, but also as an outcome survey after enzyme replacement therapy.

  • https://doi.org/10.19125/jmrd.2017.3.1.20 인용 PDF KSCI