DIAGNOSIS METHOD FOR MUCOPOLYSACCHARIDOSES
Date
2018-05
Authors
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Journal ISSN
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Publisher
University of Delaware
Abstract
Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases
caused by the deficiency of lysosomal enzyme that is required to degrade various
glycosaminoglycans (GAGs). GAGs are long unbranched polysaccharides consisting
of repeating disaccharides that include chondroitin sulfate, dermatan sulfate, heparan
sulfate, keratan sulfate, and hyaluronan. Each type of MPS is characterized by the
accumulation of specific GAG(s). In MPS, the undegraded GAGs are stored in
lysosomes and extracellular matrix (ECM) of a variety of tissues, secreted into the
bloodstream, and then excreted in the urine. Accumulated GAGs lead to cell
dysfunction and abnormal structure of ECM, causing progressive damage of multiple
tissues including CNS, lung, heart, liver, spleen, kidney, joint, and bone. There are 11
known enzyme deficiencies, resulting in seven distinct forms of MPS.
The first aim of this study was to obtain data about the epidemiology of the
different types of MPS in Japan and Switzerland and to compare with similar data
from other countries.
Overall, the frequency of MPS varies for each population due to differences in
ethnic backgrounds and/or founder effects that affect the birth prevalence of each type
of MPS, as seen for other rare genetic diseases.
The second aim was to explore clinical, radiographic, biochemical, and
molecular diagnosis and clinical assessment tests for Mucopolysaccharidosis IVA
(MPS IVA, Morquio A syndrome).
MPS IVA is one of MPS disorders inherited as an autosomal recessive trait
and caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency
of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs),
chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in
the cartilage., leading to a direct impact on bone development and successive systemic
skeletal spondylepiphyseal dysplasia. Diagnosis of MPS IVA needs clinical,
radiographic, and laboratory testing to make a complete conclusion. After
investigation, urinary and blood KS and C6S, the enzyme activity of GALNS, and
GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype
in MPS IVA.
The third aim was to determine the appropriate biomarker for screening MPS
and monitoring therapeutic efficacy.We identified significant increase of proinflammatory
factors such as cytokines and chemokines and GAGs in MPS IVB, MPS
IVA, and MPS II patients.
Overall accurate and rapid diagnosis for MPS is required to manage and treat
the patients with MPS.
Description
Keywords
Biological Sciences, diagosis, MUCOPOLYSACCHARIDOSES