title: Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder.
abstract: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfate sulfatase, which results in systemic accumulation of glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate. Accumulation of these GAGs causes characteristic features as disproportionate dwarfism associated with skeletal deformities, genu valgum, pigeon chest, joint laxity, and kyphoscoliosis. However, the pathological mechanism of systemic skeletal dysplasia and involvement of other tissues remain unanswered in the paucity of availability of an autopsied case and successive systemic analyses of multiple tissues. We report here a 20-year-old male autopsied case with MPS IVA, who developed characteristic skeletal features by the age of 1.5 years and died of acute respiratory distress syndrome five days later after occipito-C1-C2 cervical fusion. We pathohistologically analyzed postmortem tissues including trachea, lung, thyroid, humerus, aorta, heart, liver, spleen, kidney, testes, bone marrow, and lumbar vertebrae. The postmortem tissues relevant with clinical findings demonstrated 1) systemic storage materials in multiple tissues beyond cartilage, 2) severely vacuolated and ballooned chondrocytes in trachea, humerus, vertebrae, and thyroid cartilage with disorganized extracellular matrix and poor ossification, 3) appearance of foam cells and macrophages in lung, aorta, heart valves, heart muscle, trachea, visceral organs, and bone marrow, and 4) storage of chondrotin-6-sulfate in aorta. This is the first autopsied case with MPS IVA whose multiple tissues have been analyzed pathohistologically and these pathological findings should provide a new insight into pathogenesis of MPS IVA.
authors.affiliation: Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yasuda
authors.forename: Kazunari
authors.initials: K
authors.lastname: Fushimi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Katsuji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
authors.forename: Jozef
authors.initials: J
authors.lastname: Zustin
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: Bobbie
authors.initials: B
authors.lastname: Boyce
authors.forename: Terry
authors.initials: T
authors.lastname: Kokas
authors.forename: Carol
authors.initials: C
authors.lastname: Barone
authors.forename: Mary
authors.initials: M
authors.lastname: Theroux
authors.forename: William
authors.initials: W
authors.lastname: Mackenzie
authors.forename: Barbara
authors.initials: B
authors.lastname: Nagel
authors.forename: Jan S
authors.initials: JS
authors.lastname: Ryerse
authors.forename: Kenji E
authors.initials: KE
authors.lastname: Orii
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
mesh_terms: D001344:Autopsy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009085:Mucopolysaccharidosis IV / Q000175:diagnosis* / Q000209:etiology*; D010641:Phenotype; D014057:Tomography, X-Ray Computed; D055815:Young Adult