title: Morquio A syndrome: diagnosis and current and future therapies.
abstract: Morquio A syndrome is an autosomal recessive disorder, one of 50 lysosomal storage diseases (LSDs), and is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme causes specific glycosaminoglycan (GAG) accumulation: keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced in the cartilage, therefore, the undegraded substrates accumulate mainly in cartilage and in its extracelluar matrix (ECM), causing direct leads to direct impact on cartilage and bone development and leading to the resultant systemic skeletal spondyloepiphyseal dysplasia. Chondrogenesis ,the earliest phase of skeletal formation that leads to cartilage and bone formation is controlled by cellular interactions with the ECM, growth and differentiation factors and other molecules that affect signaling pathways and transcription factors in a temporal-spatial manner. In Morquio A patients, in early childhood or even at birth, the cartilage is disrupted presumably as a result of abnormal chondrogenesis and/ or endochondral ossification. The unique clinical features are characterized by a marked short stature, odontoid hypoplasia, protrusion of the chest, kyphoscoliosis, platyspondyly, coxa valga, abnormal gait, and laxity of joints. In spite of many descriptions of the unique clinical manifestations, diagnosis delay still occurs. The pathogenesis of systemic skeletal dysplasia in Morquio A syndrome remains an enigmatic challenge. In this review article, screening, diagnosis, pathogenesis and current and future therapies of Morquio A are discussed.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.forename: Eriko
authors.initials: E
authors.lastname: Yasuda
authors.forename: Pravin
authors.initials: P
authors.lastname: Patel
authors.forename: Kristen
authors.initials: K
authors.lastname: Ruhnke
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.forename: William G
authors.initials: WG
authors.lastname: Mackenzie
authors.forename: Robert
authors.initials: R
authors.lastname: Mason
authors.forename: Mihir M
authors.initials: MM
authors.lastname: Thacker
authors.forename: Mary
authors.initials: M
authors.lastname: Theroux
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Alméciga-Díaz
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Chinen
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Daniel
authors.initials: D
authors.lastname: Rowan
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Tado
authors.initials: T
authors.lastname: Orii
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D019637:Orthopedic Procedures
chemical_list: D000893:Anti-Inflammatory Agents