{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:04:01Z","timestamp":1790949841988,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T00:00:00Z","timestamp":1588118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Municipal Health Commission Fund","award":["20184Y0133"],"award-info":[{"award-number":["20184Y0133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Patients with mucopolysaccharidoses IVA (MPS IVA) have a progressive accumulation of the specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS), leading to the degeneration of the cartilage matrix and its connective tissue perturbing the regular microarchitecture of cartilage and successively distorting bone ossification and growth. Impaired cartilage quality and poor bone mineralization lead to serious hip disorders in MPS IVA patients. Although hip dysplasia is seen widely in musculoskeletal abnormality of this disorder, the pathophysiology of the hip bone and cartilage morphology in these patients remains unclear. Until now, no systemic study of the hip joints in MPS IVA has been reported by using the combined images of plain film radiographs (PFR) and Magnetic Resonance Imaging (MRI). This study aimed to assess the bony and cartilaginous features of hip joints and to explore the potentially related factors of femoral head osteonecrosis (FHN) and hip subluxation\/dislocation in patients with MPS IVA. Hip joints in MPS IVA patients were retrospectively reviewed, based on the findings of PFR and MRI data from 2014 to 2019. Demographic information was also collected and analyzed with imaging measurements. A total of 19 patients (eight boys and 11 girls) were recruited, and 38 hip joints in these patients were examined. Eleven patients (57.9%) had FHN. FHN patients were statistically compared with those without FHN. Correlations between cartilaginous femoral head coverage (CFHC) and acetabular index (AI), cartilaginous AI (CAI), or neck-shaft angle (NSA) were investigated in patients with hip subluxation or dislocation. The greater cartilaginous coverage of the hips than their osseous inherency was observed. Significant correlation was observed between CFHC and AI (r =\u22120.351, p = 0.049) or CAI (r =\u22120.381, p = 0.032). Severe subluxations or dislocations were more likely to be present in those with more dysplastic bony and cartilaginous hips. In conclusion, our study provides the first systemic description of bony and cartilaginous characteristics in the hip morphology of MPS IVA patients. We have demonstrated that plain radiography alone leads to a misunderstanding of hip morphology and that MRI measurements with PFR are an essential tool to evaluate the \u2018true\u2019 characterization of hips for MPS IVA patients.<\/jats:p>","DOI":"10.3390\/diagnostics10050264","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T13:23:45Z","timestamp":1588166625000},"page":"264","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pathophysiology of Hip Disorders in Patients with Mucopolysaccharidosis IVA"],"prefix":"10.3390","volume":"10","author":[{"given":"Zhigang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatric Orthopedics, Shanghai Children\u2019s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedics, Shanghai Children\u2019s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enze","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedics, Shanghai Children\u2019s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Shanghai Children\u2019s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-2160","authenticated-orcid":false,"given":"Shunji","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Departments of Orthopedics and BioMedical, Skeletal Dysplasia, Nemours\/Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedics, Shanghai Children\u2019s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ymgme.2016.11.007","article-title":"Mucopolysaccharidosis IVA and glycosaminoglycans","volume":"120","author":"Khan","year":"2017","journal-title":"Mol. Genet. Metab."},{"key":"ref_2","first-page":"145","article-title":"Sur uneforme de dystrophie osseusefamiliale","volume":"27","author":"Morquio","year":"1929","journal-title":"Bull. Soc. Pediatr."},{"key":"ref_3","first-page":"4","article-title":"The classics: Chondro-osteo-dystrophy: Roentgenographic and clinical features of a child with dislocation of vertebrae","volume":"114","author":"Brailsford","year":"1976","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"931","DOI":"10.2174\/138920111795542615","article-title":"Mucopolysaccharidosis Type IVA (Morquio A Disease): Clinical Review and Current Treatment: A Special Review","volume":"12","author":"Tomatsu","year":"2011","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s10545-007-0529-7","article-title":"International Morquio a Registry: Clinical manifestation and natural course of Morquio A disease","volume":"30","author":"Tomatsu","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","unstructured":"Tomatsu, S. (2018). Mucopolysaccharidosis Update, Nova Medicine and Health. 2 Volume Set."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/BPO.0000000000000463","article-title":"Characterization of Hip Morphology in Children with Mucopolysaccharidosis Types I and II","volume":"36","author":"Ashby","year":"2016","journal-title":"J. Pediatr. Orthop."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3113\/JSOA.2015.0099","article-title":"Total hip arthroplasty in very young bone marrow transplant patients","volume":"24","author":"Ledford","year":"2015","journal-title":"J. Surg. Orthop. Adv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ymgme.2013.03.004","article-title":"High prevalence of femoral head necrosis in Mucopolysaccharidosis type III (Sanfilippo disease): A national, observational, cross-sectional study","volume":"109","author":"Maas","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_10","first-page":"2314","article-title":"Idiopathic osteonecrosis of femur in adult Morquio type B disease","volume":"34","author":"Rondot","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1055\/s-2004-822663","article-title":"Epiphyseal dysplasia\u2014Symptoms and differential diagnostic aspects","volume":"142","author":"Kohler","year":"2004","journal-title":"Z. Orthop. Und Ihre Grenzgeb."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1007\/s002470050725","article-title":"Progressive bone resorption after pathological fracture of the femoral neck in Hunter\u2019s syndrome","volume":"29","author":"Ichikawa","year":"1999","journal-title":"Pediatr. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1302\/0301-620X.76B6.7983131","article-title":"Bone-marrow transplantation in Hurler\u2019s syndrome. Effect on skeletal development","volume":"76","author":"Field","year":"1994","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/01241398-198307000-00005","article-title":"Bilateral failure of the capital femoral epiphysis: Bilateral Perthes disease, multiple epiphyseal dysplasia, pseudoachondroplasia, and spondyloepiphyseal dysplasia congenita and tarda","volume":"3","author":"Crossan","year":"1983","journal-title":"J. Pediatr. Orthop."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1055\/s-2008-1037428","article-title":"Etiology and pathogenesis of epiphyseal necrosis in childhood as exemplified with the hip","volume":"134","author":"Dustmann","year":"1996","journal-title":"Z. Orthop. Und Ihre Grenzgeb."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/BPO.0000000000000858","article-title":"Hip Morphology in MPS-1H Patients: An MRI-based Study","volume":"38","author":"Breyer","year":"2018","journal-title":"J. Pediatr. Orthop."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1080\/000164701753606635","article-title":"Femoral head dysplasia in Morquio disease type A: Bilateral varus osteotomy of the femur","volume":"72","author":"Kanazawa","year":"2001","journal-title":"Acta Orthop. Scand."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.5435\/JAAOS-21-01-12","article-title":"Mucopolysaccharide Disorders in Orthopaedic Surgery","volume":"21","author":"White","year":"2013","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s11832-014-0601-4","article-title":"Orthopedic management of the extremities in patients with Morquio A syndrome","volume":"8","author":"White","year":"2014","journal-title":"J. Child. Orthop."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1302\/0301-620X.92B2.23104","article-title":"Bilateral hip replacement in three patients with lysosomal storage disease: Mucopolysaccharidosis type IV and Mucolipidosis type III","volume":"92","author":"Lewis","year":"2010","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_21","unstructured":"Bowen, J., and Kotzias-Neto, A. (2006). Developmental Dysplasia of the Hip, Data Trace Publishing. [1st ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1097\/BPO.0000000000000170","article-title":"The sphericity deviation score: A quantitative radiologic outcome measure of Legg-Calve Perthes disease applicable at the stage of healing and at skeletal maturity","volume":"34","author":"Siddesh","year":"2014","journal-title":"J. Pediatr. Orthop."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1302\/0301-620X.94B12.29958","article-title":"Development of the osseous and cartilaginous acetabular index in normal children and those with developmental dysplasia of the hip: A cross-sectional study using MRI","volume":"94","author":"Li","year":"2012","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_24","first-page":"51","article-title":"Cross-Sectional Survey of Childhood Acetabular Development in Japan","volume":"3","author":"Tsukagoshi","year":"2020","journal-title":"JMA J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/BPB.0b013e32832f5aeb","article-title":"Normal development of the hip: A geometrical analysis based on planimetric radiography","volume":"19","author":"Birkenmaier","year":"2010","journal-title":"J. Pediatr. Orthop. B"},{"key":"ref_26","first-page":"1286","article-title":"Growth charts for patients affected with Morquio A disease","volume":"146","author":"Tomatsu","year":"2008","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_27","first-page":"141","article-title":"Morquio A Syndrome: Diagnosis and Current and Future Therapies","volume":"12","author":"Tomatsu","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2214\/ajr.97.1.1","article-title":"The roentgenographic features of the KS mucopolysaccharidosis of Morquio (Morquio-Brailsford\u2019s disease)","volume":"97","author":"Langer","year":"1966","journal-title":"Am. J. Roentgenol. Radium Ther. Nucl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/ajmg.a.36833","article-title":"International guidelines for the management and treatment of Morquio A syndrome","volume":"167","author":"Hendriksz","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_30","first-page":"65","article-title":"Current and emerging treatments and surgical interventions for Morquio A syndrome: A review","volume":"2012","author":"Tomatsu","year":"2012","journal-title":"Res. Rep. Endocr. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ymgme.2015.09.007","article-title":"Obstructive airway in Morquio A syndrome, the past, the present and the future","volume":"117","author":"Tomatsu","year":"2015","journal-title":"Mol. Genet. Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s10038-019-0604-6","article-title":"Effect of enzyme replacement therapy on the growth of patients with Morquio A","volume":"64","author":"Doherty","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_33","first-page":"42","article-title":"30 months follow-up of an early enzyme replacement therapy in a severe Morquio A patient: About one case","volume":"9","author":"Cao","year":"2016","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1097\/bpo.0b013e31815a6007","article-title":"The Use of Computed Tomography to Assess Acetabular Morphology in Morquio-Brailsford Syndrome","volume":"27","author":"Borowski","year":"2007","journal-title":"J. Pediatr. Orthop."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1016\/j.bbmt.2016.08.015","article-title":"Allogeneic Hematopoietic Stem Cell Transplantation in Thirty-Four Pediatric Cases of Mucopolysaccharidosis-A Ten-Year Report from the China Children Transplant Group","volume":"22","author":"Wang","year":"2016","journal-title":"Boil. Blood Marrow Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13023-019-1074-9","article-title":"Recommendations for the management of MPS IVA: Systematic evidence- and consensus-based guidance","volume":"14","author":"Akyol","year":"2019","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e226","DOI":"10.1016\/j.bbmt.2019.02.012","article-title":"Hematopoietic Stem Cell Transplantation for Mucopolysaccharidoses: Past, Present, and Future","volume":"257","author":"Taylor","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.ymgme.2018.07.001","article-title":"Critical review of current MPS guidelines and management","volume":"126","author":"Stapleton","year":"2019","journal-title":"Mol. Genet. Metab."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/5\/264\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:51:35Z","timestamp":1760363495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/10\/5\/264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,29]]},"references-count":38,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["diagnostics10050264"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics10050264","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,29]]}}}