Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morquio syndrome (mucopolysaccharidosis IV) presents with multiple bone dysplasia and is characterized by the inability to degrade keratan sulfate due to deficient N-acetylgalactosamine-6-sulfate sulfatase in Morquio A syndrome and deficient beta-D-galactosidase in Morquio B syndrome. The aim of our study was to investigate into the pathogenetic mechanism as it is not clear whether the accumulation of keratan sulfate is toxic for osteoblasts or inhibits osteoblast activity as e.g. bone resorption. The glycosaminoglycans keratan sulfate, heparan sulfate, dermatan sulfate, chondroitin-4,6-sulfate and hyaluronic acid were tested in rat neonatal calvarian cultures for their effects on bone resorption, osteoblast activity and toxicity. Bone resorption was evaluated by calcium release into the medium, osteoblast activity by the determination of alkaline phosphatase and toxicity by measuring lactate dehydrogenase in the culture media. Keratan sulfate had no effect on bone resorption but inhibited osteoblast activity at the low, nontoxic concentration of 10 ng per ml organ culture supernatant significantly (p<0.05). At a concentration of 100 ng per ml keratan sulfate revealed toxic effects as reflected by significantly (p<0.05) elevated lactate dehydrogenase activity. None of the other glycosaminoglycans inhibited osteoblast activities. Heparan sulfate showed at toxic levels (10 microg per ml supernatant) significantly increased bone resorption (p<0.05) accompanied by increased alkaline phosphatase activity. The specific keratan sulfate effects of inhibiting osteoblast activity and toxicity towards bone, which were never tested before, suggest a role for this glycosaminoglycan in the pathogenesis of bone dysplasia in Morquio syndrome.
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PMID:The effects of acid glycosaminoglycans on neonatal calvarian cultures--a role of keratan sulfate in Morquio syndrome? 927 6

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.
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PMID:Diagnosing mucopolysaccharidosis IVA. 2337 50