chondroitin and Mucopolysaccharidosis-II

Glycosaminoglycan isolated from the urine of a patient with the Hunter syndrome was composed of heparan sulfate (59.9%), dermatan sulfate (30.6%) and chondroitin sulfate (9.5%), and was heterogeneous in molecular weight (1,500-10,000) and in sulfate content (0.35-2.05 moles/mole of hexosamine). About 60% of dermatan sulfate and 10% of heparan sulfate had molecular weight of 7,000 to 10,000, while about 10% of the former and 60% of the latter had those of 1,500 to 3,500. Sulfate contents of dermatan sulfate and heparan sulfate were inversely related to their molecular weights. Higher total- and N-sulfate contents were measured in smaller molecular-weight heparan sulfate, and higher acetyl content was in larger molecular-weight heparan sulfate. On the basis of the chemical properties of dermatan sulfate and heparan sulfate isolated in this experiment, their catabolic processes in the Hunter syndrome were discussed.

Topics: Amino Acids; Child, Preschool; Chondroitin; Dermatan Sulfate; Electrophoresis; Glycosaminoglycans; Heparitin Sulfate; Humans; Male; Molecular Weight; Mucopolysaccharidosis II

The chemical structure of dermatan sulfate (DS) in the urine of a patient the Hunter syndrome was studied through the analysis of disaccharide units which were derived from the urinary DS by digestion with chondroitinase ABC and separated on a Dowex 1 column. The DS was basically composed of repeating disaccharide units of iduronyl N-acetylgalactosamine 4-sulfate. About 90% of the excess sulfate were linked to the iduronate residues as an additional sulfate group in the unit. N-Acetylgalactosamine 6-sulfate and N-acetylgalactosamine 4,6-disulfate residues were minor components. No non-sulfated disaccharide unit was detected in the digestion products. Only sulfoiduronate residue was found as the non-reducing terminal sugar of the DS molecule, consistent with the lack of iduronosulfate sulfatase in this disease.

Topics: Acetylgalactosamine; Animals; Chemical Phenomena; Chemistry; Child, Preschool; Chondroitin; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Dermatan Sulfate; Disaccharides; Humans; Male; Mucopolysaccharidosis II; Skin; Swine

The separation and quantitative analysis of enzymatic degradation products of isomeric chondroitin sulfates by high-performance liquid chromatography (HPLC) are described. The substituted unsaturated disaccharides which result from digestion of chondroitin sulfates with chondroitinase are quickly separated on polar absorbents such as silica gel. The UV absorption properties of these unsaturated disaccharides permit UV measurement with detection limits of approximately 100 ng. Their separation by HPLC facilitates the use of enzymatic methods for the determination of chondroitin sulfates A, B and C. The potential of this method in clinical application is demonstrated by quantitative assays of glycosaminoglycans from a normal urine and urine from a patient with Hunter syndrome. The results are consistent with amount of isomeric chondroitin sulfates found in comparable urines by others.

Topics: Autoanalysis; Biodegradation, Environmental; Chondroitin; Chondroitin Sulfates; Chondroitinases and Chondroitin Lyases; Chromatography, High Pressure Liquid; Disaccharides; Glycosaminoglycans; Humans; Isomerism; Mucopolysaccharidosis II

Glycosaminoglycans were isolated from the urines of 46 patients with mucopolysaccharidosis; 11 with Type I (Hurler), 8 with Type II (Hunter), 16 with Type III (Sanfilippo A and B), 9 with Type V (Scheie), one with Type VI (Marateaux-Lamy), and one unclassified. All 46 patients excreted in their urine excessive amounts of dermatan sulfate, heparan sulfate or both. In addition, patients of certain types excreted excessive amounts of chondroitin sulfates A and/or C. There is a trend in each type of the disease towards the same carbazole/orcinol ratio, glucosamine/galactosamine ratio and glycosaminoglycan composition. Molecular weight distribution of the urinary glycosaminoglycans by gel filtration from Sephadex G-200 is characteristic for each different type of mucopolysaccharidosis and is distinguished from normal controls and patients without mucopolysaccharidosis. Preparation of elution diagrams from Sephadex G-200 allows an estimation of the composition of the glycosamino-glycans. Practically all heparan sulfate and a sizable part of dermatan sulfate from the urinary glycosaminoglycans of all these patients have been highly degraded. In all the patients in which the specific enzyme defect was demonstrated, the assignment of the type of mucopolysaccharidosis, on the basis of the elution diagrams, was correct. Patients with mucopolysaccharidosis Type V displayed two conspicuously different types of elution patterns, suggesting heterogeneity. Indeed, only a portion of these patients showed alpha-L- iduronidase deficiency. Carriers had normal urinary glycosaminoglycan output and composition and exhibited normal elution diagrams.

Topics: Adolescent; Adult; Bone and Bones; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chondroitin; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hypertrichosis; Infant; Intellectual Disability; Joint Diseases; Male; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Retinitis Pigmentosa

Arylsulfatase B deficiency was demonstrated in peripheral leukocytes, cultured skin fibroblasts, and a lymphoid line derived from a patient with MLS. The patient's parents demonstrated levels of arylsulfatase B that were intermediate between those found in patient and those in control subjects. The activity (mean plus or minus SD) in leukocytes from normal subjects, the patient's parents, and the patient was 113.7 plus or minus 36.2, 31.0, and 5.2 nmol 4-nitrocatechol/mg protein/hr, respectively. In skin fibroblasts of the same subjects the activity was 145.2 plus or minus 41.6, 58.5, and 7.0, respectively. Nine other lysosomal enzymes were normal in skin fibroblasts of the patient. No arylsulfatase B activity was detected in a lymphoid line established from the patient with MLS. The arylsulfatase B activity in cultured amniotic fluid cells from 10 normal pregnancies was 203.2 plus or minus 49.9.

Topics: Amniotic Fluid; Arylsulfatases; Cell Line; Cells, Cultured; Child, Preschool; Chondroitin; Cystic Fibrosis; Female; Fibroblasts; Galactosemias; Gaucher Disease; Glycogen Storage Disease Type II; Heterozygote; Homozygote; Humans; Leukocytes; Leukodystrophy, Metachromatic; Lymphoid Tissue; Lysosomes; Male; Metabolism, Inborn Errors; Mucopolysaccharidoses; Mucopolysaccharidosis II; Mucopolysaccharidosis VI; Pregnancy; Skin; Sulfatases

Topics: Animals; Cattle; Chondroitin; Chromatography, Ion Exchange; Deoxyribonucleases; Electrophoresis, Paper; Fibroblasts; Glycosaminoglycans; Humans; Hydrolysis; Lyases; Mucopolysaccharidosis II; Pancreas; Papain; Peptide Hydrolases; Proteus vulgaris; Retinitis Pigmentosa; Ribonucleases; Skin; Sulfatases

Topics: Ammonium Sulfate; Cells, Cultured; Chemical Precipitation; Chondroitin; Chromatography, Affinity; Chromatography, Gel; Electrophoresis; Fibroblasts; Glucosamine; Humans; Isoelectric Focusing; Macromolecular Substances; Molecular Weight; Mucopolysaccharidosis II; Proteins; Proteinuria; Retinitis Pigmentosa; Skin; Sulfates; Sulfur Isotopes; Tritium

Glycosaminoglycans were isolated from the urine of three patients with Hurler's, Hunter's and Morquio's syndromes and also from the liver and spleen of the case of Hurler's syndrome by a procedure avoiding further degradation. A method of determining the proportions of dermatan sulphate, heparan sulphate and chondroitin sulphate in each preparation is described. The relative proportions of these glycosaminoglycans in the urine and organs of the case of Hurler's syndrome were very similar. Glycosaminoglycans from the organs were of much lower molecular weight than normal, consisting of single chains of molecular weight about 5000 together with multiples of up to four such chains attached to peptide moieties. The linkage region normally attaching glycosaminoglycan chains to protein in whole protein-polysaccharides of connective tissue was degraded progressively towards serine. The total output and relative proportions of abnormal glycosaminoglycans in the urine were compared in two brothers with Hunter's syndrome examined on two occasions 4 years apart. At comparable ages they excreted about the same amount, and the relative proportions of each glycosaminoglycan remained essentially constant. The composition and chromatographic behaviour of the glycosaminoglycan in the urine from the case of Morquio's syndrome indicated that it consisted of material containing about one-third keratan sulphate and two-thirds chondroitin sulphate as part of the same molecule, as in proteoglycans of cartilage. The total output of glycosaminoglycans, although higher than normal, was considerably less than in other types of Mucopolysaccharidoses.

Topics: Amino Acids; Carbohydrates; Child; Child, Preschool; Chondroitin; Chromatography; Detergents; Glycoproteins; Glycosaminoglycans; Humans; Hyaluronoglucosaminidase; Infant; Liver; Male; Molecular Weight; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis IV; Pentoses; Pyridinium Compounds; Retinitis Pigmentosa; Solubility; Sulfates

Topics: Adult; Bone and Bones; Bronchi; Cartilage; Chondroitin; Collagen; Connective Tissue; Femur; Glycosaminoglycans; Humans; Male; Microscopy, Polarization; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Retinitis Pigmentosa; Ribs; Trachea

Topics: Child, Preschool; Chondroitin; Glycosaminoglycans; Heparin; Humans; Keratins; Male; Mucopolysaccharidosis II; Retinitis Pigmentosa

Topics: Adolescent; Child; Child, Preschool; Chondroitin; Chromatography, Ion Exchange; Electrophoresis; Humans; Mucopolysaccharidosis II; Retinitis Pigmentosa; Sulfuric Acids

Topics: Adrenal Cortex Hormones; Chondroitin; Chromosome Aberrations; Chromosome Disorders; Culture Techniques; Genes, Recessive; Heparin; Humans; Hydroxychloroquine; Lymphocytes; Mucopolysaccharidosis I; Mucopolysaccharidosis II; Sex Chromosomes; Staining and Labeling; Vitamin A

Topics: Child; Chondroitin; Female; Glycosaminoglycans; Heparin; Humans; Male; Mucopolysaccharidosis II; Radiography; Retinitis Pigmentosa