bromochloroacetic-acid and Mucopolysaccharidoses

This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA.. Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance.. Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P.. Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.

Topics: Adult; Aged; alpha 1-Antitrypsin; Biomarkers; Chondroitinsulfatases; Disease Progression; Dose-Response Relationship, Drug; Enzyme Replacement Therapy; Female; Humans; Keratins; Lipoprotein(a); Male; Middle Aged; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Serum Amyloid P-Component; Treatment Outcome; Young Adult

A method is proposed for the measurement of glycosaminoglycans (GAG) on 5-10 ml of plasma. It is based on the adsorption of GAG on small ECTEOLA columns followed by measurement of the hexuronic acid in the NaCl eluates. Routine use of the method has indicated the presence of a GAG fraction that adsorbs readily on ECTEOLA ("free" GAG) and of another that adsorbs on it only after treatment with papain ("bound" GAG). "Free" and "bound" GAG have been measured in normal adults, normal children, and children affected by mucopolysaccharidosis type I; the results obtained are in good agreement with those previously reported in the literature.Various analyses performed on purified "free" and "bound" GAG have confirmed that chondroitin-4-sulfate is the main glycosaminoglycan of normal human plasma where it occurs both free and bound to protein and at various levels of sulfation. The presence of small amounts of heparan sulfate and keratan sulfate has also been demonstrated. Metabolic experiments performed in rabbits have indicated that plasma GAG derive from peripheral tissues and increase sharply after papain injection. In young animals the "free" GAG have a faster turnover than the "bound," possibly a reflection of active processes of remodeling and calcification. The synthesis of the "free" and "bound" GAG, as measured with (85)S-sulfate incorporation, seems to proceed at the same rate, and the hypothesis has been advanced that as a result of the action of tissue proteases, part of the "bound" GAG may be transformed into "free" GAG, the latter being immediately extruded from the tissues into the circulatory system.

Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Chondroitin; Chromatography; Collagen Diseases; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronoglucosaminidase; In Vitro Techniques; Keratins; Male; Methods; Mucopolysaccharidoses; Papain; Rabbits; Spectrophotometry; Sulfur Isotopes

Topics: Adolescent; Bone Diseases; Child; Chondroitin; Cleidocranial Dysplasia; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Intellectual Disability; Keratins; Male; Mucopolysaccharidoses; Osteitis Deformans; Osteogenesis Imperfecta; Scoliosis

Topics: Child; Child, Preschool; Cytoplasmic Granules; Female; Histocytochemistry; Humans; Keratins; Liver; Macrophages; Male; Membranes; Microscopy, Electron; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Sulfates