chondroitin and Dwarfism

Glycosaminoglycans, including chondroitin, dermatan, and heparan sulfate, have various roles in a wide range of biological events such as cell signaling, cell proliferation, tissue morphogenesis, and interactions with various growth factors. Their polysaccharides covalently attach to the serine residues on specific core proteins through the common linker region tetrasaccharide, -xylose-galactose-galactose-glucuronic acid, which is produced through the stepwise addition of respective monosaccharides by four distinct glycosyltransferases. Mutations in the human genes encoding the glycosyltransferases responsible for the biosynthesis of the linker region tetrasaccharide cause a number of genetic disorders, called glycosaminoglycan linkeropathies, including Desbuquois dysplasia type 2, spondyloepimetaphyseal dysplasia, Ehlers-Danlos syndrome, and Larsen syndrome. This review focused on recent studies on genetic diseases caused by defects in the biosynthesis of the common linker region tetrasaccharide.

Topics: Cell Proliferation; Chondroitin; Craniofacial Abnormalities; Dermatan Sulfate; Dwarfism; Ehlers-Danlos Syndrome; Glycosyltransferases; Heparitin Sulfate; Humans; Joint Instability; Morphogenesis; Mutation; Ossification, Heterotopic; Osteochondrodysplasias; Polydactyly

Topics: Autopsy; Carbohydrate Metabolism, Inborn Errors; Chondroitin; Chromosome Aberrations; Chromosome Disorders; Dwarfism; Fibroblasts; Glycosaminoglycans; Histocytochemistry; Humans; Hyaluronic Acid; Intellectual Disability; Joint Diseases; Metaplasia; Microscopy, Electron; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Osteochondritis; Retinitis Pigmentosa

A 14-year-old boy was found to excrete excessive amounts of acidic glycosaminoglycans which were predominantly chondroitin 4-sulfate and chondroitin 6-sulfate. Clinical features included dwarfism, mental retardation, coarse facies, deformities of the spine, hip joints and thorax, and granulations in leucocytes. The clinical and biochemical features found in this boy were compared with the known types of mucopolysaccharidosis and it has been concluded that this case is a new type of mucopolysacchariduria.

Topics: Adolescent; Chondroitin; Chondroitin Sulfates; Dwarfism; Glycosaminoglycans; Humans; Intellectual Disability; Male; Mucopolysaccharidoses

Incorporation of 35SO42- into adenosine 5'-phosphosulfate (APS), 3'-phosphoadenosine 5'-phosphosulfate (PAPS), and chondroitin sulfate was simultaneously assessed with extracts prepared from epiphyseal cartilage of neonatal normal or homozygous brachymorphic mice. Radioactivity measured in APS, PAPS, and chondroitin sulfate of extracts from brachymorphic cartilage was approximately 300%, 9%, and 13% of the normal levels, respectively. Even though more APS accumulated in the mutant cartilage extracts, APS actually synthesized (total 35SO42- incorporated into APS, PAPS, and macromolecular products) was only 17% of that in the normal. However, of the amount synthesized, 90% and 55% of newly synthesized APS were converted to PAPS by cartilage extracts of normal and brachymorphic mice, respectively. Specific assays for ATP sulfurylase (sulfate adenylyltransferase; ATP:sulfate adenylyltransferase, EC 2.7.7.4) and APS kinase (adenylylsulfate kinase; ATP:adenylylsulfate 3'-phosphotransferase, EC 2.7.1.25) showed that the sulfurylase enzyme activity is reduced to approximately 1/2 and the kinase to approxomately 1/14 in brachymorphic mice. These results suggest that the production of an undersulfated proteoglycan in brachymorphic cartilage results from a defective conversion of APS to PAPS.

Topics: Adenine Nucleotides; Adenosine Phosphosulfate; Animals; Cartilage; Chondroitin; Chondroitin Sulfates; Dwarfism; Mice; Phosphoadenosine Phosphosulfate; Phosphotransferases; Sulfates; Sulfurtransferases

Topics: Animals; Cattle; Cattle Diseases; Chondroitin; Chromatography, Gas; Chromatography, Ion Exchange; Dermatan Sulfate; Dwarfism; Electrophoresis, Cellulose Acetate; Glycosaminoglycans; Hexosamines; Mucopolysaccharidoses; Uronic Acids

Topics: Child; Child, Preschool; Chondroitin; Dwarfism; Female; Glycosaminoglycans; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphopenia; Mucopolysaccharidoses; Nephrotic Syndrome; Radiography; Spectrum Analysis

Topics: Chondroitin; Craniofacial Dysostosis; Dwarfism; Famous Persons; France; History, 19th Century; History, 20th Century; Humans; Paintings; Syndrome

Topics: Biopsy; Bone Diseases, Developmental; Cartilage; Cetylpyridinium; Child; Chondroitin; Collagen; Dwarfism; Endoplasmic Reticulum; Female; Glycosaminoglycans; Hexosamines; Humans; Hydroxyproline; Ilium; Microscopy, Electron; Osteoblasts; Osteocytes; Proteins; Ulna

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

Topics: Achondroplasia; Adolescent; Biopsy; Carbohydrate Metabolism, Inborn Errors; Cartilage; Child; Chondroitin; Collagen; Dwarfism; Dwarfism, Pituitary; Female; Galactosamine; Glycosaminoglycans; Growth Disorders; Hexosamines; Hexoses; Histocytochemistry; Humans; Hydroxyproline; Hypophosphatemia, Familial; Male; Myxedema; Proteins; Pyridinium Compounds; Tibia; Turner Syndrome

Topics: Adolescent; Chondroitin; Corneal Opacity; Craniofacial Dysostosis; Diagnosis, Differential; Dwarfism; Encephalocele; Female; Humans; Mucopolysaccharidoses; Pneumoencephalography; Syndrome

Topics: Adolescent; Bone and Bones; Carbohydrate Metabolism, Inborn Errors; Child; Child, Preschool; Chondroitin; Craniofacial Dysostosis; Dwarfism; Epiphyses; Female; Glycosaminoglycans; Humans; Male; Radiography

Topics: Adolescent; Child; Child, Preschool; Chondroitin; Diagnosis, Differential; Dwarfism; Female; Glycosaminoglycans; Humans; Mucopolysaccharidosis IV; Radiography; Sulfates

Topics: Carbohydrate Metabolism, Inborn Errors; Child, Preschool; Chondroitin; Dwarfism; Female; Glycosaminoglycans; Humans; Infant; Intellectual Disability; Male; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Retinitis Pigmentosa