{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:43:51Z","timestamp":1790419431953,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,8]],"date-time":"2020-03-08T00:00:00Z","timestamp":1583625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Mucolipidosis type II (MLII) is a rare lysosomal storage disorder caused by defective trafficking of lysosomal enzymes. Severe skeletal manifestations are a hallmark of the disease including hip dysplasia. This study aims to describe hip morphology and the natural course of hip pathologies in MLII by systematic evaluation of plain radiographs, ultrasounds and magnetic resonance imaging (MRI). An international two-centered study was performed by retrospective chart review. All MLII patients with at least one pelvic radiograph were included. A total of 16 patients were followed over a mean of 3.5 years (range 0.2\u201310.7 years). Typical age-dependent radiographic signs identified were femoral cloaking (7\/16), rickets\/hyperparathyroidism-like changes (6\/16) and constrictions of the supra-acetabular part of the os ilium (16\/16) and the femoral neck (7\/16). The course of acetabular and migration indexes (AI, MI) significantly increased in female patients. However, in the overall group, there was no relevant progression of acetabular dysplasia with a mean AI of 23.0 (range 5\u00b0\u201341\u00b0) and 23.7\u00b0 (range 5\u00b0\u201340\u00b0) at the first and last assessments, respectively. Better knowledge on hip morphology in MLII could lead to earlier diagnosis, improved clinical management and enables assessment of effects of upcoming therapies on the skeletal system.<\/jats:p>","DOI":"10.3390\/jcm9030728","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T05:37:34Z","timestamp":1583732254000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hip Morphology in Mucolipidosis Type II"],"prefix":"10.3390","volume":"9","author":[{"given":"Luise Sophie","family":"Ammer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"International Center for Lysosomal Disorders, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Oussoren","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole Maria","family":"Muschol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"International Center for Lysosomal Disorders, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7409-7042","authenticated-orcid":false,"given":"Sandra","family":"Pohl","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Estela","family":"Rubio-Gozalbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Genetics, Maastricht University Medical Center, 6211 LK Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Santer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Stuecker","sequence":"additional","affiliation":[{"name":"International Center for Lysosomal Disorders, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Department of Pediatric Orthopedics, Children\u2019s Hospital Altona, 22763 Hamburg, Germany"},{"name":"Department of Orthopedics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3737-6402","authenticated-orcid":false,"given":"Eik","family":"Vettorazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Rafaela","family":"Breyer","sequence":"additional","affiliation":[{"name":"International Center for Lysosomal Disorders, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"},{"name":"Department of Pediatric Orthopedics, Children\u2019s Hospital Altona, 22763 Hamburg, Germany"},{"name":"Department of Orthopedics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ejcb.2009.10.008","article-title":"Mannose phosphorylation in health and disease","volume":"89","author":"Kollmann","year":"2010","journal-title":"Eur. J. Cell Biol."},{"key":"ref_2","first-page":"842","article-title":"The lysosomal storage disorders mucolipidosis type II, type III alpha\/beta, and type III gamma: Update on GNPTAB and GNPTG mutations","volume":"40","author":"Velho","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ymgme.2006.03.003","article-title":"When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients","volume":"88","author":"Bargal","year":"2006","journal-title":"Mol. Genet. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/ajmg.a.32193","article-title":"Molecular order in mucolipidosis II and III nomenclature","volume":"146A","author":"Cathey","year":"2008","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/nm1305","article-title":"Mucolipidosis II is caused by mutations in GNPTA encoding the alpha\/beta GlcNAc-1-phosphotransferase","volume":"11","author":"Tiede","year":"2005","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1111\/j.1440-1754.2010.01715.x","article-title":"The natural history and osteodystrophy of mucolipidosis types II and III","volume":"46","author":"Briody","year":"2010","journal-title":"J. Paediatr. Child Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1136\/jmg.2009.067736","article-title":"Phenotype and genotype in mucolipidoses II and III alpha\/beta: A study of 61 probands","volume":"47","author":"Cathey","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/ejhg.2013.207","article-title":"A novel intermediate mucolipidosis II\/IIIalphabeta caused by GNPTAB mutation in the cytosolic N-terminal domain","volume":"22","author":"Leroy","year":"2014","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_9","unstructured":"Adam, M.P., and Pagon, A.H. (2008). GNPTAB-Related Disorders. GeneReviews\u00ae, University of Washington. (Updated 2019)."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1126\/science.157.3790.804","article-title":"Mutant enzymatic and cytological phenotypes in cultured human fibroblasts","volume":"157","author":"Leroy","year":"1967","journal-title":"Science"},{"key":"ref_11","first-page":"113","article-title":"The genetic mucolipidoses. Diagnosis and differential diagnosis","volume":"9","author":"Spranger","year":"1970","journal-title":"Humangenetik"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.2214\/ajr.129.1.37","article-title":"Neonatal mucolipidosis II (I-cell disease): Clinical and radiologic features in three cases","volume":"129","author":"Patriquin","year":"1977","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2214\/ajr.118.1.213","article-title":"Roentgenographic manifestations of Leroy\u2019s I-cell disease","volume":"118","author":"Taber","year":"1973","journal-title":"Am. J. Roentgenol. Radium Ther. Nucl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1007\/s00247-016-3673-0","article-title":"Early characteristic radiographic changes in mucolipidosis II","volume":"46","author":"Lai","year":"2016","journal-title":"Pediatric Radiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hefti, F. (1997). Kinderorthop\u00e4die in der Praxis, Springer. [1st ed.].","DOI":"10.1007\/978-3-662-08078-8"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/ort.1980.51.suppl-184.01","article-title":"The stability of the hip in children. A radiological study of the results of muscle surgery in cerebral palsy","volume":"184","author":"Reimers","year":"1980","journal-title":"Acta Orthop. Scand Suppl."},{"key":"ref_17","first-page":"39","article-title":"Normal values of the hip joint for the evaluation of X-rays in children and adults","volume":"119","author":"Tonnis","year":"1976","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/BPO.0000000000000791","article-title":"Normal Percentile Reference Curves and Correlation of Acetabular Index and Acetabular Depth Ratio in Children","volume":"38","author":"Novais","year":"2018","journal-title":"J. Pediatric Orthop."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1007\/s11999-014-4038-3","article-title":"What are the radiographic reference values for acetabular under- and overcoverage?","volume":"473","author":"Tannast","year":"2015","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1302\/0301-620X.92B9.25094","article-title":"Shenton\u2019s line","volume":"92","author":"Jones","year":"2010","journal-title":"J. Bone Jt. Surg. Br."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/BF00436138","article-title":"Classification of hip joint dysplasia by means of sonography","volume":"102","author":"Graf","year":"1984","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.18637\/jss.v082.i13","article-title":"lmerTest Package: Tests in Linear Mixed Effects Models","volume":"82","author":"Kuznetsova","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1055\/s-0039-1697605","article-title":"Clinical Characterization of Mucolipidoses II and III: A Multicenter Study","volume":"8","author":"Alegra","year":"2019","journal-title":"J. Pediatric Genet."},{"key":"ref_24","first-page":"797","article-title":"I-cell disease (mucolipidosis II): A lysosomopathy","volume":"54","author":"Blank","year":"1974","journal-title":"Pediatrics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1399-0004.1985.tb00388.x","article-title":"I-cell disease: Clinical studies of 21 Japanese cases","volume":"28","author":"Okada","year":"1985","journal-title":"Clin. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1001\/archpedi.1975.02120460063016","article-title":"I-cell disease. Report of three cases","volume":"129","author":"Terashima","year":"1975","journal-title":"Am. J. Dis. Child"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/00003086-198404000-00005","article-title":"Recent advances in the prevention, early diagnosis, and treatment of congenital dislocation of the hip in Japan","volume":"184","author":"Yamamuro","year":"1984","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Siffert, R.S. (1981). Patterns of deformity of the developing hip. Clin. Orthop. Relat. Res., 14\u201329.","DOI":"10.1097\/00003086-198110000-00002"},{"key":"ref_29","first-page":"283","article-title":"Mucolipidosis II (I-cell disease): Present status of knowledge","volume":"11","author":"Leroy","year":"1975","journal-title":"Birth Defects Orig. Artic. Ser."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/BF00686161","article-title":"I-cell disease (mucolipidosis II): A report on its pathology","volume":"33","author":"Martin","year":"1975","journal-title":"Acta Neuropathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/00003086-199203000-00040","article-title":"Bone changes of mucolipidosis II at different ages. Postmortem study of three cases","volume":"276","author":"Pazzaglia","year":"1992","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/S0022-3476(78)81218-9","article-title":"Neonatal presentation of I-cell disease","volume":"93","author":"Spritz","year":"1978","journal-title":"J. Pediatric"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1002\/emmm.201302979","article-title":"Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II","volume":"5","author":"Kollmann","year":"2013","journal-title":"EMBO Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1126\/science.1205677","article-title":"A key enzyme in the biogenesis of lysosomes is a protease that regulates cholesterol metabolism","volume":"333","author":"Marschner","year":"2011","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1136\/pgmj.49.571.359","article-title":"I-cell disease--mucolipidosis II","volume":"49","author":"Gordon","year":"1973","journal-title":"Postgrad Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.ocl.2005.12.001","article-title":"Growth and development of the child\u2019s hip","volume":"37","author":"Lee","year":"2006","journal-title":"Orthop. Clin. N. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/BF02387638","article-title":"Mucolipidosis II: Correlation between radiological features and histopathology of the bones","volume":"19","author":"Pazzaglia","year":"1989","journal-title":"Pediatric Radiol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/3\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:05:15Z","timestamp":1760173515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/3\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,8]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["jcm9030728"],"URL":"https:\/\/doi.org\/10.3390\/jcm9030728","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,8]]}}}