title: The clinical spectrum and pathophysiology of skeletal complications in lysosomal storage disorders.
abstract: Lysosomal storage disorders affect multiple organs including the skeleton. Disorders with prominent skeletal symptoms are type 1 and 3 Gaucher disease, the mucopolysaccharidoses, the glycoproteinoses and pycnodysostosis. Clinical manifestations range from asymptomatic radiographical evidence of bone pathology to overt bone crises (Gaucher), short stature with typical imaging features known as dysostosis multiplex (MPS), with spine and joint deformities (mucopolysaccharidoses, mucolipidosis), or osteopetrosis with pathological fractures (pynodysostosis). The pathophysiology of skeletal disease is only partially understood and involves direct substrate storage, inflammation and other complex alterations of cartilage and bone metabolism. Current treatments are enzyme replacement therapy, substrate reduction therapy and hematopoietic stem cell transplantation. However, effects of these interventions on skeletal disease manifestations are less well established and outcomes are highly dependent on disease burden at treatment initiation. It is now clear that adjunctive treatments that target skeletal disease are needed and should be part of future research agenda.
authors.affiliation: Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: lclarke@cfri.ca.
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Clarke
authors.affiliation: Department of Internal Medicine/Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Electronic address: c.e.hollak@amc.nl.
authors.forename: Carla E M
authors.initials: CE
authors.lastname: Hollak
mesh_terms: D001842:Bone and Bones / Q000378:metabolism*; D002356:Cartilage / Q000378:metabolism*; D004413:Dysostoses / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D056947:Enzyme Replacement Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D010020:Osteonecrosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D010024:Osteoporosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D058631:Pycnodysostosis / Q000209:etiology / Q000378:metabolism* / Q000628:therapy
keywords: Gaucher disease; bone crisis; bone involvement; dysosotosis multiplex; lysosomal storage disorders; mucolipidosis; mucopolysaccharidosis; osteonecrosis; osteoporosis; pycnodysostosis