title: Abnormal neuronal metabolism and storage in mucopolysaccharidosis type VI (Maroteaux-Lamy) disease.
abstract: Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy disease, is an inherited disorder of glycosaminoglycan catabolism caused by deficient activity of the lysosomal hydrolase, N-acetylgalactosamine 4-sulphatase (4S). A variety of prominent visceral and skeletal defects are characteristic, but primary neurological involvement has generally been considered absent. We report here that the feline model of MPS VI exhibits abnormal lysosomal storage in occasional neurones and glia distributed throughout the cerebral cortex. Abnormal lysosomal inclusions were pleiomorphic with some resembling zebra bodies and dense core inclusions typical of other MPS diseases or the membranous storage bodies characteristic of the gangliosidoses. Pyramidal neurones were shown to contain abnormal amounts of GM2 and GM3 gangliosides by immunocytochemical staining and unesterified cholesterol by histochemical (filipin) staining. Further, Golgi staining of pyramidal neurones revealed that some possessed ectopic axon hillock neurites and meganeurites similar to those described in Tay-Sachs and other neuronal storage diseases with ganglioside storage. Some animals evaluated in this study also received allogeneic bone marrow transplants, but no significant differences in neuronal storage were noted between treated and untreated individuals. These studies demonstrate that deficiency of 4S activity can lead to metabolic abnormalities in the neurones of central nervous system in cats, and that these changes may not be readily amenable to correction by bone marrow transplantation. Given the close pathological and biochemical similarities between feline and human MPS VI, it is conceivable that children with this disease have similar neuronal involvement.
authors.affiliation: Department of Neuroscience, Rose F. Kennedy Center for Research in Mental Retardation and Human Development, Albert Einstein College of Medicine, Bronx, NY 10461, USA. walkley@aecom.yu.edu
authors.forename: S U
authors.initials: SU
authors.lastname: Walkley
authors.forename: M A
authors.initials: MA
authors.lastname: Thrall
authors.forename: M E
authors.initials: ME
authors.lastname: Haskins
authors.forename: T W
authors.initials: TW
authors.lastname: Mitchell
authors.forename: D A
authors.initials: DA
authors.lastname: Wenger
authors.forename: D E
authors.initials: DE
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Dial
authors.forename: H
authors.initials: H
authors.lastname: Seim
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002415:Cats; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005732:Gangliosides / Q000378:metabolism; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009087:Mucopolysaccharidosis VI / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D005732:Gangliosides; D002784:Cholesterol