A defect in the metabolic activation of sulfate in a patient with achondrogenesis type IB.

Détails

ID Serval
serval:BIB_46FC9856A34B
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Titre
A defect in the metabolic activation of sulfate in a patient with achondrogenesis type IB.
Périodique
American Journal of Human Genetics
Auteur(s)
Superti-Furga A.
ISSN
0002-9297 (Print)
ISSN-L
0002-9297
Statut éditorial
Publié
Date de publication
1994
Volume
55
Numéro
6
Pages
1137-1145
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Achondrogenesis type I is a perinatally lethal, short-limb chondrodysplasia. Two types, IA and IB, have been distinguished by radiographic and histological criteria; both types appear to be inherited as autosomal recessive traits. The underlying molecular defects are not known, but histochemical studies have suggested that in achondrogenesis type IB, cartilage matrix is deficient in sulfated proteoglycans. We have studied cartilage extracts of one newborn with achondrogenesis type IB and found that proteoglycans were quantitatively reduced, and, unlike in control cartilage, they did not stain with toluidine blue and did not bind to DEAE. Impaired synthesis of sulfated proteoglycans was observed also in fibroblast cultures of the achondrogenesis IB patient. Radioactive labeling and immunoprecipitation studies indicated that core protein and side chains of proteoglycans were synthesized normally but were not sulfated. Analysis of sulfate metabolism in fibroblast cultures showed, in the patient's cells, normal intracellular levels of free sulfate but markedly reduced levels of the two intermediate compounds in the sulfate activation pathway, adenosine-phosphosulfate and phosphoadenosine-phosphosulfate. The results can be explained by deficient activity of one of the enzymes responsible for the biologic activation of sulfate, possibly similar to that observed in cartilage (but not in skin) of the recessive, nonlethal mouse mutant brachymorphic and leading to defective sulfation of macromolecules. Expression of the sulfation defect in cultured fibroblasts may offer a diagnostic tool for the disorder.
Mots-clé
Adenosine Phosphosulfate/analysis, Adult, Biotransformation, Bone and Bones/pathology, Bone and Bones/radiography, Cartilage/enzymology, Cartilage/metabolism, Cells, Cultured, Female, Fibroblasts, Growth Plate/pathology, Humans, Infant, Newborn, Male, Osteochondrodysplasias/classification, Osteochondrodysplasias/enzymology, Phosphoadenosine Phosphosulfate/analysis, Proteoglycans/biosynthesis, Sulfates/metabolism, Sulfotransferases/metabolism
Pubmed
Web of science
Création de la notice
14/03/2011 17:14
Dernière modification de la notice
03/03/2018 16:48
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