{"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":1790949841995,"version":"4.1.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100017950","name":"Shanghai Municipal Health Commission","doi-asserted-by":"crossref","award":["202240361"],"award-info":[{"award-number":["202240361"]}],"id":[{"id":"10.13039\/100017950","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shanghai Science & Technology Commission","award":["20ZR1446300"],"award-info":[{"award-number":["20ZR1446300"]}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"crossref","award":["20152520"],"award-info":[{"award-number":["20152520"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic variants in the N-acetylgalactosamine-6-sulfatase (\n                      <jats:italic>GALNS<\/jats:italic>\n                      ) gene and is characterized by progressive and multi-system involvements, dominantly with skeletal deformities. A mild form of MPS IVA often presents with atypical symptoms and can go unrecognized for years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The diagnosis of MPS IVA was confirmed via GALNS enzyme activity testing in leukocytes. Clinical features were collected. Molecular analysis was performed by next generation sequence and Sanger sequencing of the\n                      <jats:italic>GALNS<\/jats:italic>\n                      gene. The pathogenicity of the deep intron variant was verified by mRNA analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen patients with mild MPS IVA from six families were included. All probands first visit pediatric orthopedists and it took 5.6 years to be diagnosed after the disease onset. The most common symptoms in our series were waddling gait (85%), short neck (69%) and flat feet (62%). Radiologic findings indicated skeletal abnormalities in all patients, especially modification of the vertebral bodies (100%) and acetabular and femoral head dysplasia (100%). Five novel\n                      <jats:italic>GALNS<\/jats:italic>\n                      variants, including c.121-2_121-1insTTTGCTGGCATATGCA, E2 deletion, c.569\u00a0A\u2009&gt;\u2009G, c.898\u2009+\u20092 T\u2009&gt;\u2009A, and c.1139\u2009+\u20092 T\u2009&gt;\u2009C, were identified. The most common variant, a deep intron variant NM_000512.5: c.121\u2013210\u00a0C\u2009&gt;\u2009T (NM_001323544.2: c.129\u00a0C\u2009&gt;\u2009T, p.G43G), was revealed to result in an 11\u00a0bp deletion (c.128_138delGCGATGCTGAG, p.Gly43Aspfs*5) on\n                      <jats:italic>GALNS<\/jats:italic>\n                      mRNA in the\n                      <jats:italic>GALNS<\/jats:italic>\n                      transcript of NM_001323544.2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides significant insights into the clinical features and molecular characteristics that contribute to the early diagnosis of mild MPS IVA. On the basis of our cohort, orthopedists need to be able to recognize signs and symptoms of mild MPS IVA as well as the molecular and biochemical diagnosis so that an early diagnosis and treatment can be instituted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-024-01910-x","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T06:07:19Z","timestamp":1717394839000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Delayed diagnosis of mild mucopolysaccharidosis type IVA"],"prefix":"10.1186","volume":"17","author":[{"given":"Mengni","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinquan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiwen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"1910_CR1","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/0006-291X(74)91022-5","volume":"61","author":"R Matalon","year":"1974","unstructured":"Matalon R, Arbogast B, Justice P, Brandt IK, Dorfman A. Morquio\u2019s syndrome: deficiency of a chondroitin sulfate N-acetylhexosamine sulfate sulfatase. Biochem Biophys Res Commun. 1974;61:759\u201365.","journal-title":"Biochem Biophys Res Commun"},{"key":"1910_CR2","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":"1910_CR3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.ymgme.2013.04.009","volume":"109","author":"E Yasuda","year":"2013","unstructured":"Yasuda E, Fushimi K, Suzuki Y, Shimizu K, Takami T, Zustin J, et al. Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder. Mol Genet Metab. 2013;109:301\u201311.","journal-title":"Mol Genet Metab"},{"key":"1910_CR4","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":"1910_CR5","doi-asserted-by":"publisher","first-page":"931","DOI":"10.2174\/138920111795542615","volume":"12","author":"S Tomatsu","year":"2011","unstructured":"Tomatsu S, Monta\u00f1o AM, Oikawa H, Smith M, Barrera L, Chinen Y, et al. Mucopolysaccharidosis type IVA (Morquio A disease): clinical review and current treatment. Curr Pharm Biotechnol. 2011;12:931\u201345.","journal-title":"Curr Pharm Biotechnol"},{"key":"1910_CR6","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/jimd.12491","volume":"45","author":"M Yi","year":"2022","unstructured":"Yi M, Wang Y, Gao X, Han L, Qiu W, Gu X, et al. Investigation of GALNS variants and genotype-phenotype correlations in a large cohort of patients with mucopolysaccharidosis type IVA. J Inherit Metab Dis. 2022;45:593\u2013604.","journal-title":"J Inherit Metab Dis"},{"key":"1910_CR7","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/humu.9265","volume":"24","author":"S Tomatsu","year":"2004","unstructured":"Tomatsu S, Filocamo M, Orii KO, Sly WS, Gutierrez MA, Nishioka T, et al. Mucopolysaccharidosis IVA (Morquio A): identification of novel common mutations in the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene in Italian patients. Hum Mutat. 2004;24:187\u20138.","journal-title":"Hum Mutat"},{"key":"1910_CR8","doi-asserted-by":"publisher","first-page":"45","DOI":"10.2147\/TACG.S141881","volume":"11","author":"SM Tapiero-Rodriguez","year":"2018","unstructured":"Tapiero-Rodriguez SM, Acosta Guio JC, Porras-Hurtado GL, Garc\u00eda N, Solano M, Pachajoa H, et al. Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA. Appl Clin Genet. 2018;11:45\u201357.","journal-title":"Appl Clin Genet"},{"key":"1910_CR9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.gene.2019.04.026","volume":"704","author":"B T\u00fcys\u00fcz","year":"2019","unstructured":"T\u00fcys\u00fcz B, Alkaya DU, Toksoy G, Gunes N, Yildirim T, Bayhan \u0130A, et al. Mutation spectrum and pivotal features for differential diagnosis of Mucopolysaccharidosis IVA patients with severe and attenuated phenotype. Gene. 2019;704:59\u201367.","journal-title":"Gene"},{"key":"1910_CR10","first-page":"96","volume":"52","author":"E Baker","year":"1993","unstructured":"Baker E, Guo XH, Orsborn AM, Sutherland GR, Callen DF, Hopwood JJ, et al. The morquio a syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3. Am J Hum Genet. 1993;52:96\u20138.","journal-title":"Am J Hum Genet"},{"key":"1910_CR11","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1006\/geno.1993.1266","volume":"16","author":"M Masuno","year":"1993","unstructured":"Masuno M, Tomatsu S, Nakashima Y, Hori T, Fukuda S, Masue M, et al. Mucopolysaccharidosis IV A: assignment of the human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) gene to chromosome 16q24. Genomics. 1993;16:777\u20138.","journal-title":"Genomics"},{"key":"1910_CR12","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1006\/geno.1994.1132","volume":"20","author":"Y Nakashima","year":"1994","unstructured":"Nakashima Y, Tomatsu S, Hori T, Fukuda S, Sukegawa K, Kondo N, et al. Mucopolysaccharidosis IV A: molecular cloning of the human N-acetylgalactosamine-6-sulfatase gene (GALNS) and analysis of the 5\u2019-flanking region. Genomics. 1994;20:99\u2013104.","journal-title":"Genomics"},{"key":"1910_CR13","doi-asserted-by":"publisher","first-page":"1384","DOI":"10.1002\/humu.24270","volume":"42","author":"A Zanetti","year":"2021","unstructured":"Zanetti A, D\u2019Avanzo F, AlSayed M, Brusius-Facchin AC, Chien YH, Giugliani R, et al. Molecular basis of mucopolysaccharidosis IVA (Morquio A syndrome): a review and classification of GALNS gene variants and reporting of 68 novel variants. Hum Mutat. 2021;42:1384\u201398.","journal-title":"Hum Mutat"},{"key":"1910_CR14","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1002\/humu.22635","volume":"35","author":"A Morrone","year":"2014","unstructured":"Morrone A, Caciotti A, Atwood R, Davidson K, Du C, Francis-Lyon P, et al. Morquio A syndrome-associated mutations: a review of alterations in the GALNS gene and a new locus-specific database. Hum Mutat. 2014;35:1271\u20139.","journal-title":"Hum Mutat"},{"key":"1910_CR15","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s10545-013-9587-1","volume":"36","author":"TC Wood","year":"2013","unstructured":"Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ, et al. Diagnosing mucopolysaccharidosis IVA. J Inherit Metab Dis. 2013;36:293\u2013307.","journal-title":"J Inherit Metab Dis"},{"key":"1910_CR16","first-page":"487","volume":"47","author":"H Li","year":"2009","unstructured":"Li H, Ji CY, Zong XN, Zhang YQ. [Height and weight standardized growth charts for Chinese children and adolescents aged 0 to 18 years]. Zhonghua Er Ke Za Zhi. 2009;47:487\u201392.","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"1910_CR17","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/0009-8981(90)90339-T","volume":"187","author":"OP van Diggelen","year":"1990","unstructured":"van Diggelen OP, Zhao H, Kleijer WJ, Janse HC, Poorthuis BJ, van Pelt J, et al. A fluorimetric enzyme assay for the diagnosis of Morquio disease type A (MPS IV A). Clin Chim Acta. 1990;187:131\u20139.","journal-title":"Clin Chim Acta"},{"key":"1910_CR18","first-page":"414","volume":"51","author":"J Ye","year":"2013","unstructured":"Ye J, Lei HL, Zhang HW, Qiu WJ, Han LS, Wang Y, et al. [Analysis of GALNS gene mutation in thirty-eight Chinese patients with mucopolysaccharidosis type IVA]. Zhonghua Er Ke Za Zhi. 2013;51:414\u20139.","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"1910_CR19","unstructured":"Liu Q, Teng Y, Niu Y, Liu Q, Duan H, Bin P et al. [Study on the influence factors of human peripheral blood B lymphocyte transformation by Epstein-Barr virus]. Wei Sheng Yan Jiu. 2009;38:528\u2009\u2013\u200930, 534."},{"key":"1910_CR20","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/j.1365-2184.2006.00363.x","volume":"39","author":"AS Mello","year":"2006","unstructured":"Mello AS, Burin MG, Michellin K, Viapiana M, Giugliani R, Coelho JC, et al. Epstein-Barr virus-induced transformation of B cells for the diagnosis of genetic metabolic disorders\u2013enumerative conditions for cryopreservation. Cell Prolif. 2006;39:29\u201336.","journal-title":"Cell Prolif"},{"key":"1910_CR21","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s12881-018-0694-6","volume":"19","author":"A Caciotti","year":"2018","unstructured":"Caciotti A, Tonin R, Mort M, Cooper DN, Gasperini S, Rigoldi M, et al. Mis-splicing of the GALNS gene resulting from deep intronic mutations as a cause of Morquio a disease. BMC Med Genet. 2018;19:183.","journal-title":"BMC Med Genet"},{"key":"1910_CR22","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1002\/ajmg.a.32281","volume":"146A","author":"AM Monta\u00f1o","year":"2008","unstructured":"Monta\u00f1o AM, Tomatsu S, Brusius A, Smith M, Orii T. Growth charts for patients affected with Morquio A disease. Am J Med Genet A. 2008;146A:1286\u201395.","journal-title":"Am J Med Genet A"},{"key":"1910_CR23","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1002\/humu.20257","volume":"26","author":"S Tomatsu","year":"2005","unstructured":"Tomatsu S, Monta\u00f1o AM, Nishioka T, Gutierrez MA, Pe\u00f1a OM, Tranda Firescu GG, et al. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). Hum Mutat. 2005;26:500\u201312.","journal-title":"Hum Mutat"},{"key":"1910_CR24","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1186\/s13023-020-01618-y","volume":"15","author":"C Ficicioglu","year":"2020","unstructured":"Ficicioglu C, Matalon DR, Luongo N, Menello C, Kornafel T, Degnan AJ. Diagnostic journey and impact of enzyme replacement therapy for mucopolysaccharidosis IVA: a sibling control study. Orphanet J Rare Dis. 2020;15:336.","journal-title":"Orphanet J Rare Dis"},{"key":"1910_CR25","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/88099","volume":"19","author":"EN Noensie","year":"2001","unstructured":"Noensie EN, Dietz HC. A strategy for disease gene identification through nonsense-mediated mRNA decay inhibition. Nat Biotechnol. 2001;19:434\u20139.","journal-title":"Nat Biotechnol"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-024-01910-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-024-01910-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-024-01910-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T06:08:45Z","timestamp":1717394925000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-024-01910-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,3]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1910"],"URL":"https:\/\/doi.org\/10.1186\/s12920-024-01910-x","relation":{},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,3]]},"assertion":[{"value":"19 February 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Informed consent was obtained from patients or legal guardians of patients in the study. All procedures were performed under the Ethics Committee of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine approval (XHEC-D-2014-006).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patients\u2019 informed consents contain their permission to publish patient data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"151"}}