{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T19:07:08Z","timestamp":1773860828968,"version":"3.50.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"BioMarin Pharmaceuticals Espa\u00f1a SL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme <jats:italic>N<\/jats:italic>-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults.<\/jats:p>\n                <jats:p>The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5\u201340.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106\u2013136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea\/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03\u20132.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68\u20133.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25\u20132.34) versus 2.25 (1.62\u20133.00) in patients not treated with ERT.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13023-021-02074-y","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T14:09:27Z","timestamp":1636121367000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience"],"prefix":"10.1186","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1026-4854","authenticated-orcid":false,"given":"Pilar","family":"Quijada-Fraile","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Arranz Canales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Mart\u00edn-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Juliana","family":"Ballesta-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Encarna","family":"Guill\u00e9n-Navarro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillem","family":"Pintos-Morell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Molt\u00f3-Abad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Moreno-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Garc\u00eda Morillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Blasco-Alonso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Luz","family":"Couce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Gil S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisenda","family":"Cort\u00e8s-Saladelafont","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica A.","family":"L\u00f3pez Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Teresa","family":"Garc\u00eda-Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Montserrat","family":"Morales Conejo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,3]]},"reference":[{"key":"2074_CR1","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3390\/diagnostics10030172","volume":"10","author":"F Kubaski","year":"2020","unstructured":"Kubaski F, De Oliveira PF, Michelin-Tirelli K, Burin MG, Rojas-M\u00e1laga D, Brusius-Facchin AC, et al. Diagnosis of mucopolysaccharidoses. Diagnostics. 2020;10:172.","journal-title":"Diagnostics"},{"key":"2074_CR2","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s13052-018-0553-2","volume":"44","author":"M Filocamo","year":"2018","unstructured":"Filocamo M, Tomanin R, Bertola F, Morrone A. Biochemical and molecular analysis in mucopolysaccharidoses: what a paediatrician must know. Ital J Pediatr. 2018;44:35\u201345.","journal-title":"Ital J Pediatr"},{"key":"2074_CR3","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ymgme.2013.04.002","volume":"110","author":"CJ Hendriksz","year":"2013","unstructured":"Hendriksz CJ, Harmatz P, Beck M, Jones S, Wood T, Lachman R, et al. Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013;110:54\u201364.","journal-title":"Mol Genet Metab"},{"key":"2074_CR4","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s10545-007-0529-7","volume":"30","author":"AM Monta\u00f1o","year":"2007","unstructured":"Monta\u00f1o AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. 2007;30:165\u201374.","journal-title":"J Inherit Metab Dis"},{"key":"2074_CR5","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.ymgme.2012.03.006","volume":"106","author":"S Pajares","year":"2012","unstructured":"Pajares S, Alcalde C, Couce ML, Del Toro M, Gonz\u00e1lez-Meneses A, Guill\u00e9n E, et al. Molecular analysis of mucopolysaccharidosis IVA (Morquio A) in Spain. Mol Genet Metab. 2012;106:196\u2013201.","journal-title":"Mol Genet Metab"},{"key":"2074_CR6","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ymgme.2018.05.004","volume":"125","author":"H Peracha","year":"2018","unstructured":"Peracha H, Sawamoto K, Averill L, Kecskemethy H, Theroux M, Thacker M, et al. Molecular genetics and metabolism, special edition: diagnosis. Diagnosis and prognosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2018;125:18\u201337.","journal-title":"Mol Genet Metab"},{"key":"2074_CR7","doi-asserted-by":"publisher","first-page":"931","DOI":"10.2174\/138920111795542615","volume":"12","author":"S Tomatsu","year":"2011","unstructured":"Tomatsu S, Montano A, Oikawa H, Rowan D, Smith M, Barrera L, et al. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment: a special review. Curr Pharm Biotechnol. 2011;12:931\u201345.","journal-title":"Curr Pharm Biotechnol"},{"key":"2074_CR8","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.ymgme.2016.05.018","volume":"119","author":"CJ Hendriksz","year":"2016","unstructured":"Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Solano Villarreal ML, et al. Long-term endurance and safety of elosulfase alfa enzyme replacement therapy in patients with Morquio A syndrome. Mol Genet Metab. 2016;119:131\u201343.","journal-title":"Mol Genet Metab"},{"key":"2074_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-020-01545-y","volume":"15","author":"L Moisan","year":"2020","unstructured":"Moisan L, Iannuzzi D, Maranda B, Campeau PM, Mitchell JJ. Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study. Orphanet J Rare Dis. 2020;15:1\u201311.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR10","first-page":"17","volume":"218","author":"ML Couce","year":"2018","unstructured":"Couce ML, del Toro M, Garc\u00eda-Jim\u00e9nez MC, Gutierrez-Solana L, Hermida-Ameijeiras \u00c1, L\u00f3pez-Rodr\u00edguez M, et al. Transition from pediatric care to adult care for patients with mucopolysaccharidosis. Rev Cl\u00ednica Espa\u00f1ola (English Ed). 2018;218:17\u201321.","journal-title":"Rev Cl\u00ednica Espa\u00f1ola (English Ed)"},{"key":"2074_CR11","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s13023-019-1074-9","volume":"14","author":"MU Akyol","year":"2019","unstructured":"Akyol MU, Alden TD, Amartino H, Ashworth J, Belani K, Berger KI, et al. Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance. Orphanet J Rare Dis. 2019;14:137.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10198-016-0780-7","volume":"17","author":"J L\u00f3pez-Bastida","year":"2016","unstructured":"L\u00f3pez-Bastida J, Oliva-Moreno J, Linertov\u00e1 R, Serrano-Aguilar P. Social\/economic costs and health-related quality of life in patients with rare diseases in Europe. Eur J Heal Econ. 2016;17:1\u20135.","journal-title":"Eur J Heal Econ"},{"key":"2074_CR13","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s13023-017-0730-1","volume":"12","author":"KR Bogart","year":"2017","unstructured":"Bogart KR, Irvin VL. Health-related quality of life among adults with diverse rare disorders. Orphanet J Rare Dis. 2017;12:177.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR14","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ymgme.2013.06.008","volume":"110","author":"VC D\u0169ng","year":"2013","unstructured":"D\u0169ng VC, Tomatsu S, Monta\u00f1o AM, Gottesman G, Bober MB, Mackenzie W, et al. Mucopolysaccharidosis IVA: correlation between genotype, phenotype and keratan sulfate levels. Mol Genet Metab. 2013;110:129\u201338.","journal-title":"Mol Genet Metab"},{"key":"2074_CR15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.ymgme.2013.01.021","volume":"109","author":"P Harmatz","year":"2013","unstructured":"Harmatz P, Mengel KE, Giugliani R, Valayannopoulos V, Lin S-P, Parini R, et al. The Morquio A clinical assessment program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab. 2013;109:54\u201361.","journal-title":"Mol Genet Metab"},{"key":"2074_CR16","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.ymgmr.2018.03.009","volume":"15","author":"G Pintos-Morell","year":"2018","unstructured":"Pintos-Morell G, Blasco-Alonso J, Couce ML, Guti\u00e9rrez-Solana LG, Guill\u00e9n-Navarro E, O\u2019Callaghan M, et al. Elosulfase alfa for mucopolysaccharidosis type IVA: real-world experience in 7 patients from the Spanish Morquio-A early access program. Mol Genet Metab Rep. 2018;15:116\u201320.","journal-title":"Mol Genet Metab Rep"},{"key":"2074_CR17","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13023-017-0634-0","volume":"12","author":"D Hughes","year":"2017","unstructured":"Hughes D, Giugliani R, Guffon N, Jones SA, Mengel KE, Parini R, et al. Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa. Orphanet J Rare Dis. 2017;12:98.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR18","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1002\/ajmg.a.38014","volume":"173","author":"PR Harmatz","year":"2017","unstructured":"Harmatz PR, Mengel E, Geberhiwot T, Muschol N, Hendriksz CJ, Burton BK, et al. Impact of elosulfase alfa in patients with Morquio A syndrome who have limited ambulation: an open-label, phase 2 study. Am J Med Genet A. 2017;173:375\u201383.","journal-title":"Am J Med Genet A"},{"key":"2074_CR19","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.ymgme.2018.02.011","volume":"123","author":"C Hendriksz","year":"2018","unstructured":"Hendriksz C, Santra S, Jones SA, Geberhiwot T, Jesaitis L, Long B, et al. Safety, immunogenicity, and clinical outcomes in patients with Morquio A syndrome participating in 2 sequential open-label studies of elosulfase alfa enzyme replacement therapy (MOR-002\/MOR-100), representing 5 years of treatment. Mol Genet Metab. 2018;123:479\u201387.","journal-title":"Mol Genet Metab"},{"key":"2074_CR20","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.ymgme.2017.11.015","volume":"123","author":"CJ Hendriksz","year":"2018","unstructured":"Hendriksz CJ, Parini R, AlSayed MD, Raiman J, Giugliani R, Mitchell JJ, et al. Impact of long-term elosulfase alfa on activities of daily living in patients with Morquio A syndrome in an open-label, multi-center, phase 3 extension study. Mol Genet Metab. 2018;123:127\u201334.","journal-title":"Mol Genet Metab"},{"key":"2074_CR21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/ajmg.a.36833","volume":"167","author":"CJ Hendriksz","year":"2015","unstructured":"Hendriksz CJ, Berger KI, Giugliani R, Harmatz P, Kampmann C, Mackenzie WG, et al. International guidelines for the management and treatment of Morquio A syndrome. Am J Med Genet A. 2015;167:11\u201325.","journal-title":"Am J Med Genet A"},{"key":"2074_CR22","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/1750-1172-9-32","volume":"9","author":"CJ Hendriksz","year":"2014","unstructured":"Hendriksz CJ, Lavery C, Coker M, Ucar SK, Jain M, Bell L, et al. Burden of disease in patients with Morquio A syndrome: results from an international patient-reported outcomes survey. Orphanet J Rare Dis. 2014;9:32.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s13023-016-0503-2","volume":"11","author":"CJ Hendriksz","year":"2016","unstructured":"Hendriksz CJ, Berger KI, Lampe C, Kircher SG, Orchard PJ, Southall R, et al. Health-related quality of life in mucopolysaccharidosis: looking beyond biomedical issues. Orphanet J Rare Dis. 2016;11:119.","journal-title":"Orphanet J Rare Dis"},{"key":"2074_CR24","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/8904_2014_396","volume":"20","author":"N Ali","year":"2015","unstructured":"Ali N, Cagle S. Psychological health in adults with Morquio syndrome. JIMD Rep. 2015;20:87\u201393.","journal-title":"JIMD Rep"},{"key":"2074_CR25","first-page":"2116","volume":"20","author":"J Esteve-Vives","year":"1993","unstructured":"Esteve-Vives J, Batlle-Gualda E, Reig A. Grupo para la adaptaci\u00f3n del HAQ a la poblaci\u00f3n Espa\u00f1ola. Spanish version of the Health Assessment Questionnaire: reliability validity and transcultural equivalency. J Rheumatol. 1993;20:2116\u201322.","journal-title":"J Rheumatol"},{"key":"2074_CR26","unstructured":"Spanish Society of Rheumatology. HAQ questionnaire [Internet]. 2015 [cited 2021 Jun 10]. Available from: https:\/\/www.ser.es\/wp-content\/uploads\/2015\/03\/HAQ_INDICE.pdf."},{"key":"2074_CR27","first-page":"789","volume":"9","author":"J Fries","year":"1982","unstructured":"Fries J, Spitz P, Young D. The dimensions of health outcomes: the Health Assessment Questionnaire disability and pain scales. J Rheumatol. 1982;9:789\u201393.","journal-title":"J Rheumatol"},{"key":"2074_CR28","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","volume":"310","author":"World Medical Association Declaration of Helsinki","year":"2013","unstructured":"World Medical Association Declaration of Helsinki. JAMA. 2013;310:2191.","journal-title":"JAMA"},{"key":"2074_CR29","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1080\/105294199277860","volume":"6","author":"JR Dixon","year":"1999","unstructured":"Dixon JR. The international conference on harmonization good clinical practice guideline. Qual Assur. 1999;6:65\u201374.","journal-title":"Qual Assur"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02074-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-021-02074-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-02074-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T14:12:12Z","timestamp":1636121532000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-02074-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,3]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2074"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-02074-y","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,3]]},"assertion":[{"value":"19 February 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethics Committee of the University Hospital12 de Octubre, Madrid. In addition, the study was conducted in accordance with the Declaration of Helsinki [], the International Conference on Harmonisation Guideline for Good Clinical Practice [], and the Spanish regulations. All patients were given information about the study both verbally and in writing, and all gave informed consent before entering the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PQF, EMH, EAC, SGM, JBA, RGS, ECS, MTGS and MALR have no competing interests. MMC received honoraria for lectures from the Takeda Pharmaceutical Company (Takeda), Sanofi Genzyme, Vitaflo International (Vitaflo), and BioMarin Pharmaceutical Inc. (BioMarin). GPM received honoraria for lectures and\/or consulting and travel support from Takeda, Sanofi, BioMarin, Amicus Therapeutics (Amicus), Kyowa Kirin International, Alexion Pharmaceuticals (Alexion) and Vitaflo. MMA received research support from Takeda, Sanofi Genzyme, Amicus, Kaleido, and Vitaflo, and fees from Sanofi Genzyme, Takeda, Alexion, and Amicus for participation in their respective registries. EGN received research and meeting support from BioMarin, Sanofi Genzyme, Takeda, and Alnylam Pharmaceuticals. DMM received travel grants from Amicus, Sanofi and Takeda.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"464"}}