title: Spontaneous mucolipidosis in a cat: an animal model of human I-cell disease.
abstract: A 7-month-old female cat was seen for abnormal facial features and abnormality of gait. Facial dysmorphism, large paws in relation to body size, dysostosis multiplex, and poor growth were noted, and mucopolysaccharidosis was suspected. A negative urine test for sulfated glycosaminoglycans and extreme stiffness of skin indicated a mucolipidosis hitherto unknown in animals. Deficiency of UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) activity was demonstrated in leukocytes and cultured fibroblasts, which had the appearance of inclusion cells (I-cells). Activities of a set of lysosomal hydrolases were abnormally low in fibroblasts and excessive in blood plasma. Postmortem morphology revealed lysosomal inclusions predominantly in fibroblasts but also in endothelial cells and chondrocytes, i.e., in cells of mesenchymal origin. Storage lysosomes contained oligosaccharides, mucopolysaccharides, and lipids. Tissues most affected were bones, cartilage, skin, and other connective tissues such as those in heart valves, aortic wall, and vocal cords. Parenchymal cells of liver and kidney were unaffected, as was skeletal muscle. Only a few of the cerebral cortical neurons had lipid inclusions; in sciatic nerve some axons were affected, but other peripheral nerves were normal. There were striking clinical, biochemical, and morphologic similarities between the disorder in this cat and the human I-cell disease.
authors.affiliation: Department of Pediatrics, University of Zürich, Switzerland.
authors.forename: N U
authors.initials: NU
authors.lastname: Bosshard
authors.forename: M
authors.initials: M
authors.lastname: Hubler
authors.forename: S
authors.initials: S
authors.lastname: Arnold
authors.forename: J
authors.initials: J
authors.lastname: Briner
authors.forename: M A
authors.initials: MA
authors.lastname: Spycher
authors.forename: H J
authors.initials: HJ
authors.lastname: Sommerlade
authors.forename: K
authors.initials: K
authors.lastname: von Figura
authors.forename: R
authors.initials: R
authors.lastname: Gitzelmann
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D001824:Body Constitution / Q000502:physiology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D002371:Cat Diseases / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D002415:Cats / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005684:Gait / Q000502:physiology; D006025:Glycosaminoglycans / Q000652:urine; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007962:Leukocytes / Q000737:chemistry / Q000473:pathology; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D009081:Mucolipidoses / Q000175:diagnosis / Q000378:metabolism / Q000662:veterinary*; D011859:Radiography; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology; D012584:Sciatic Nerve / Q000473:pathology / Q000648:ultrastructure; D012867:Skin / Q000473:pathology / Q000648:ultrastructure; D017855:Transferases (Other Substituted Phosphate Groups) / Q000032:analysis / Q000172:deficiency / Q000502:physiology; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000032:analysis / Q000172:deficiency / Q000502:physiology
chemical_list: D006025:Glycosaminoglycans; D014537:Uridine Diphosphate N-Acetylglucosamine; D017855:Transferases (Other Substituted Phosphate Groups); C030012:UDP-N-acetylglucosamine-lysosomal-enzyme-N-acetylglucosaminephosphotransferase