DIAGNOSIS METHOD FOR MUCOPOLYSACCHARIDOSES

Date
2018-05
Journal Title
Journal ISSN
Volume Title
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
Citation