chondroitin and Mucopolysaccharidosis-I

Topics: Chondroitin; Chromatography, Ion Exchange; Electrophoresis; Ethanol; Female; Glycosaminoglycans; Humans; Male; Mucopolysaccharidosis I

Topics: Acetates; Amino Acids; Child; Child, Preschool; Chondroitin; Connective Tissue; Culture Techniques; Fibroblasts; Galactosidases; Glucuronidase; Glycosaminoglycans; Glycoside Hydrolases; Hexosamines; Humans; Infant; Liver; Mucopolysaccharidosis I; Polysaccharides; Skin; Spleen; Sulfates; Sulfur Isotopes; Sulfuric Acids; Time Factors; Tritium; Uronic Acids

Topics: Arachnodactyly; Arteriosclerosis; Arthritis; Arthritis, Rheumatoid; Biochemical Phenomena; Biochemistry; Carbohydrate Metabolism; Chondroitin; Connective Tissue; Eye Diseases; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Marfan Syndrome; Mucopolysaccharidosis I; Myxedema; Osteochondrodysplasias; Pathology

alpha-L-Iduronidase activity was assayed by incubation of a radiolabelled disaccharide, O-(alpha-L-idopyranosyluronic acid)-(1----3)-2,5 anhydro-D-[1,3H]-talitol 4-sulfate (IdoA-anT4S) derived from dermatan sulfate, with homogenates of leucocytes, cultured amniotic cells and skin fibroblasts from normal individuals and patients affected with an alpha-L-iduronidase-deficiency disorder (mucopolysaccharidosis type I, MPS I), parents of such patients and patients affected with other mucopolysaccharidoses. The assay clearly distinguished affected homozygotes from normal controls, heterozygotes and other mucopolysaccharidosis types. Preliminary results show that fibroblast homogenates from patients with the MPS I Hurler phenotype were virtually unable to hydrolyse IdoA-anT4S, whereas fibroblast homogenates from a patient with a relatively mild (Scheie) phenotype exhibited a residual activity with Vmax value of 2.5 pmol/min/mg protein and an apparent Km of 21 mumol/l compared to a range of 1020-2105 pmol/min/mg for Vmax and 12-35 mumol/l for Km for fibroblasts from normal controls.

Topics: Amniotic Fluid; Cells, Cultured; Chondroitin; Dermatan Sulfate; Disaccharides; Glycoside Hydrolases; Humans; Iduronidase; Kinetics; Leukocytes; Mucopolysaccharidosis I; Prenatal Diagnosis; Skin; Structure-Activity Relationship; Substrate Specificity

Contamination of amniotic fluid cell cultures by maternal cells can be expected to lead to misdiagnosis of fetal genotype in 0.1 to 0.5/100 cultures, when assays are carried out directly on cultured cells. Chemical analysis of the cell-free amniotic fluid supernatant may overcome this source of error and has the added advantages of speed and independence from amniotic cell culture failure. We describe a pregnancy at risk for Hurler's disease where amniotic cells cultured at amniocentesis had a female karyotype and an alpha-iduronidase activity towards both phenyl and 4-methylumbelliferyl substrates at the lower end of the normal range, suggesting a heterozygous fetus. An affected fetus was predicted, however, because of a high concentration of dermatan sulphate in the amniotic fluid. The discrepancy between these findings was shown to be due to maternal cell contamination of amniotic fluid cell cultures by the birth of a male infant with Hurler's disease.

Topics: Amniotic Fluid; Cells, Cultured; Chondroitin; Dermatan Sulfate; Electrophoresis; Female; Glycoside Hydrolases; Humans; Iduronidase; Infant, Newborn; Male; Mucopolysaccharidosis I; Pregnancy; Prenatal Diagnosis

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

Topics: Chondroitin; Diagnosis, Differential; Female; Galactosidases; Glycoside Hydrolases; Heterozygote; Hexosaminidases; Humans; Iduronidase; Leukocytes; Male; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis III; Syndrome

Topics: Acid Phosphatase; Adult; Biopsy; Chondroitin; Elastic Tissue; Electroretinography; Female; Fibroblasts; Galactosidases; Glucuronidase; Glycoproteins; Glycoside Hydrolases; Hexosaminidases; Humans; Male; Mucopolysaccharidoses; Mucopolysaccharidosis I; Visual Acuity

Topics: Blood Transfusion; Chondroitin; Corneal Opacity; Glycosaminoglycans; Humans; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis IV; Retinitis Pigmentosa; Sulfates; Syndrome

Lymphoid suspension lines have been established from three patients with the Hurler syndrome and four normals. The Hurler lines can be distinguished from normals by (a) staining characteristics, (b) increase in total cellular mucopolysaccharide content, and (c) increase in dermatan sulfate. Hyaluronic acid is absent in cultured lymphoid cells from normal persons and patients with the Hurler syndrome. The availability of biochemically marked suspension cultures should prove useful for enzymatic studies as well as for further elucidation of this clinical syndrome.

Topics: Carbohydrate Metabolism, Inborn Errors; Cell Line; Cells, Cultured; Chemical Precipitation; Chondroitin; Electrophoresis; Fibroblasts; Glycosaminoglycans; Histocytochemistry; Humans; Hyaluronic Acid; In Vitro Techniques; Lymphoid Tissue; Mucopolysaccharidosis I; Pyridinium Compounds; Skin; Staining and Labeling; Uronic Acids

Topics: Adult; Carbohydrate Metabolism, Inborn Errors; Chondroitin; Eczema; Female; Fibroma; Glycosaminoglycans; Hip Dislocation, Congenital; Humans; Mucopolysaccharidosis I; Muscle Spasticity; Nevus, Pigmented; Psoriasis; Quadriplegia; Retinitis Pigmentosa; Skin Neoplasms; Syndrome

Topics: Blood Chemical Analysis; Bone and Bones; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chondroitin; Corneal Opacity; Deafness; Diagnosis, Differential; Dwarfism; Facial Expression; Female; Glycosaminoglycans; Heart Diseases; Humans; Infant; Intellectual Disability; Male; Mucopolysaccharidosis I; Mucopolysaccharidosis IV; Radiography; Retinitis Pigmentosa

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: Animals; Carbazoles; Carbohydrate Metabolism, Inborn Errors; Chondroitin; Chromatography, Gel; Circular Dichroism; Glycosaminoglycans; Heparin; Humans; Indoles; Intellectual Disability; Molecular Weight; Mucopolysaccharidosis I; Optical Rotatory Dispersion; Rats; Resorcinols; Sulfuric Acids; Ultraviolet Rays

Topics: Amino Acids; Aspartic Acid; Bone and Bones; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chondroitin; Chromatography, Ion Exchange; Female; Galactosamine; Glucosamine; Glutamates; Glycine; Glycosaminoglycans; Humans; Hypertrichosis; Joint Diseases; Male; Mucopolysaccharidosis I; Retinitis Pigmentosa; Serine; Uronic 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; Humans; Mucopolysaccharidosis I; Sulfates

Topics: Child, Preschool; Chondroitin; Female; Glycosaminoglycans; Humans; Metabolism, Inborn Errors; Mucopolysaccharidosis I; Sulfates

Topics: Adolescent; Child; Child, Preschool; Chondroitin; Female; Humans; Intellectual Disability; Male; Mucopolysaccharidosis I; Radiography

Topics: Brain Chemistry; Chondroitin; Glycolipids; Glycosaminoglycans; Histocytochemistry; Humans; Mucopolysaccharidosis I; Neurons

Topics: Adolescent; Adult; Child; Child, Preschool; Chondroitin; Electrophoresis; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Male; Mucopolysaccharidosis I

Topics: Biopsy; Child, Preschool; Chondroitin; Glycosaminoglycans; Heparinoids; Hepatomegaly; Humans; Intellectual Disability; Lysosomes; Male; Microscopy, Electron; Mucopolysaccharidosis I

Topics: Adolescent; Child; Chondroitin; Chromatography, Paper; Female; Glycosaminoglycans; Humans; Male; Mucopolysaccharidosis I

Topics: Body Height; Child; Chondroitin; Fingers; Humans; Intelligence; Male; Metacarpus; Mucopolysaccharidosis I; Phenotype; Radiography; Spine

Topics: Adolescent; Biochemical Phenomena; Biochemistry; Biomedical Research; Child; Chondroitin; Electrophoresis; Fluids and Secretions; Genetics, Medical; Glycosaminoglycans; Humans; Mucopolysaccharidosis I; Urine

Topics: Biochemical Phenomena; Biochemistry; Child; Chondroitin; Chromatography; Electrophoresis; Glycolipids; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Metabolism, Inborn Errors; Mucopolysaccharidoses; Mucopolysaccharidosis I; Osteochondrodysplasias; Urine; Urticaria Pigmentosa

The biosynthesis of the acid mucopolysaccharides, hyaluronic acid and chondroitin sulfuric acid, occurs by way of uridine nucleotides which contain the monosaccharide units of the respective polysaccharides. The mechanism of alternation of groups is as yet unknown. Certain of the acid mucopolysaccharides are covalently bound to protein by way of serine. In the case of the protein-polysaccharide complex of cartilage, there is evidence to suggest that the polysaccharide may be linked to the serine by way of galactose. Chondroitin sulfuric acid B may be isolated almost free of amino acids from the tissues and urine of patients with the Hurler syndrome without the use of proteolytic enzymes, acid, or alkali. This contrasts markedly with the tight binding of this compound to protein in normal tissue. It is suggested that the metabolic defect in this disease may reside in a defect of the peptide or linkage of the peptide to polysaccharide resulting in failure of the acid mucopolysaccharide to be fixed normally in connective tissue. Such a defect may result in interference with normal regulation of polysaccharide synthesis with a resultant increased synthesis. It is proposed that such a mechanism may obtain in other heritable connective tissue diseases as well as other storage diseases.

Topics: Carbohydrate Metabolism; Cartilage; Chondroitin; Connective Tissue; Glycosaminoglycans; Humans; Hyaluronic Acid; Metabolism; Mucopolysaccharidosis I; Nucleotides; Proteins; Research

Topics: Child; Chondroitin; Chromosome Aberrations; Chromosome Disorders; Corneal Dystrophies, Hereditary; Glycosaminoglycans; Hearing Disorders; Mucopolysaccharidosis I; Sex

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Aminohydrolases; Brain; Carotenoids; Child; Chondroitin; Diffuse Cerebral Sclerosis of Schilder; Gangliosides; Glucosyltransferases; Histocytochemistry; Humans; Infant; Kidney; Lipid Metabolism; Liver; Metabolic Diseases; Mucopolysaccharidosis I; Phosphotransferases; Rats; Research; Sulfatases; Sulfates; Sulfur Isotopes; Tuberous Sclerosis

Topics: Arachnodactyly; Bone and Bones; Brain; Cartilage; Child; Chondroitin; Glycosaminoglycans; Humans; Kidney; Liver; Marfan Syndrome; Metabolism; Mucopolysaccharidosis I; Spleen; Syndrome