title: Mucopolysaccharidosis IVA and glycosaminoglycans.
abstract: Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA.
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: Shaukat
authors.initials: S
authors.lastname: Khan
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Alméciga-Díaz
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sawamoto
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: William G
authors.initials: WG
authors.lastname: Mackenzie
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Theroux
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Pizarro
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.affiliation: Department of Pediatrics, Gifu University, Gifu, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
authors.affiliation: Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, United States; Department of Pediatrics, Gifu University, Gifu, Japan; Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, United States. Electronic address: stomatsu@nemours.org.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
mesh_terms: D000293:Adolescent; D000328:Adult; D002356:Cartilage / Q000378:metabolism*; D002986:Clinical Trials as Topic; D056947:Enzyme Replacement Therapy; D005260:Female; D015316:Genetic Therapy; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D019637:Orthopedic Procedures
chemical_list: D006025:Glycosaminoglycans
keywords: Chondroitin-6-sulfate; Keratan sulfate; Mucopolysaccharidosis IVA; N-acetylgalactosamine-6-sulfate sulfatase; Skeletal dysplasia