{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:09:18Z","timestamp":1792001358567,"version":"4.4.0"},"reference-count":23,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2022,1,4]]},"abstract":"<jats:p>X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.<\/jats:p>","DOI":"10.3233\/jnd-210712","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T13:03:05Z","timestamp":1628254985000},"page":"73-82","source":"Crossref","is-referenced-by-count":43,"title":["Intrahepatic Cholestasis Is a Clinically Significant Feature Associated with Natural History of X-Linked Myotubular Myopathy (XLMTM): A Case Series and Biopsy Report"],"prefix":"10.1177","volume":"9","author":[{"given":"Cristina","family":"Molera","sequence":"first","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition Department, Hospital Sant Joan de D\u00e9u, Universidad de Barcelona, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinatin","family":"Sarishvili","sequence":"additional","affiliation":[{"name":"Pediatric Department, Medical Center Mrcheveli, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Unidadde Patolog\u00eda Neuromuscular, Servicio de Neurolog\u00eda Pedi\u00e1trica, Hospital Sant Joan de D\u00e9u, Universidad de Barcelona, CIBERER, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irakli","family":"Rtskhiladze","sequence":"additional","affiliation":[{"name":"Pediatric Department, Medical Center Mrcheveli, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Mu\u00f1oz Bartolo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hepatology, Hospital Universitario La Paz, Madrid, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Fern\u00e1ndez Cebri\u00e1n","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Gastroenterolog\u00eda, Hepatolog\u00eda y Nutrici\u00f3n Pedi\u00e1trica. Departamento de Pediatr\u00eda. Complexo Hospitalario Universitario de Ourense, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justo","family":"Valverde Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Gastroenterolog\u00eda, Hepatolog\u00eda y Nutrici\u00f3n Pedi\u00e1trica UGC Pediatr\u00eda. Hospital Infantil Virgen del Rocio, Sevilla, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Mu\u00f1oz Cabello","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Neuropediatr\u00eda, Hospital Infantil Virgen del Roc\u00edo, Sevilla, Espa\u00f1a"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Graham","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weston","family":"Miller","sequence":"additional","affiliation":[{"name":"Astellas Gene Therapies, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Sepulveda","sequence":"additional","affiliation":[{"name":"Astellas Gene Therapies, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binita M.","family":"Kamath","sequence":"additional","affiliation":[{"name":"The Hospital for Sick Children and University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine and Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/JND-210712_ref2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.molmed.2012.04.004","article-title":"Myotubularin phosphoinositide phosphatases: Cellular functions and disease pathophysiology","volume":"18","author":"Hnia","year":"2012","journal-title":"Trends Mol Med"},{"issue":"9","key":"10.3233\/JND-210712_ref3","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.nmd.2018.06.012","article-title":"An integrated modelling methodology for estimating the prevalence of centronuclear myopathy","volume":"28","author":"Vandersmissen","year":"2018","journal-title":"Neuromuscul Disord"},{"issue":"16","key":"10.3233\/JND-210712_ref4","doi-asserted-by":"crossref","first-page":"e1852","DOI":"10.1212\/WNL.0000000000007319","article-title":"X-linked myotubular myopathy: A prospective international natural history study","volume":"92","author":"Annoussamy","year":"2019","journal-title":"Neurology"},{"issue":"4","key":"10.3233\/JND-210712_ref5","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/mus.26018","article-title":"A multicenter, retrospective medical record review of X-linked myotubular myopathy: The RECENSUS study","volume":"57","author":"Beggs","year":"2018","journal-title":"Muscle Nerve"},{"issue":"2","key":"10.3233\/JND-210712_ref7","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S0022-3476(99)70417-8","article-title":"Medical complications in long-term survivors with X-linked myotubular myopathy","volume":"134","author":"Herman","year":"1999","journal-title":"J Pediatr"},{"issue":"13","key":"10.3233\/JND-210712_ref8","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1212\/WNL.0000000000004415","article-title":"A natural history study of X-linked myotubular myopathy","volume":"89","author":"Amburgey","year":"2017","journal-title":"Neurology"},{"issue":"15-16","key":"10.3233\/JND-210712_ref9","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1089\/hum.2020.217","article-title":"Re: \u201cMoving Forward After Two Deaths in a Gene Therapy Trial of Myotubular Myopathy\u201d by Wilson and Flotte","volume":"31","author":"Shieh","year":"2020","journal-title":"Hum Gene Ther"},{"issue":"2","key":"10.3233\/JND-210712_ref10","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/jnen\/nlv020","article-title":"Skeletal muscle pathology in X-linked myotubular myopathy: Review with cross-species comparisons","volume":"75","author":"Lawlor","year":"2016","journal-title":"J Neuropathol Exp Neurol"},{"issue":"5","key":"10.3233\/JND-210712_ref11","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ejhg.2012.201","article-title":"Expanding the MTM1 mutational spectrum: Novel variants including the first multi-exonic duplication and development of a locus-specific database","volume":"21","author":"Oliveira","year":"2013","journal-title":"Eur J Hum Genet"},{"issue":"3","key":"10.3233\/JND-210712_ref12","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1148\/radiol.2020201513","article-title":"Normal Liver Stiffness Measured with MR Elastography in Children","volume":"297","author":"Trout","year":"2020","journal-title":"Radiology"},{"issue":"1","key":"10.3233\/JND-210712_ref14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jceh.2013.10.005","article-title":"Progressive familial intrahepatic cholestasis","volume":"4","author":"Srivastava","year":"2014","journal-title":"J Clin Exp Hepatol"},{"issue":"5","key":"10.3233\/JND-210712_ref15","doi-asserted-by":"crossref","first-page":"318","DOI":"10.14740\/gr873e","article-title":"A Fatal Case of Intra-Abdominal Hemorrhage Following Diagnostic Blind Percutaneous Liver Biopsy in a Patient With Peliosis Hepatis","volume":"10","author":"Biswas","year":"2017","journal-title":"Gastroenterology Res"},{"issue":"12","key":"10.3233\/JND-210712_ref16","doi-asserted-by":"crossref","first-page":"165958","DOI":"10.1016\/j.bbadis.2020.165958","article-title":"Recent advances in understanding the molecular mechanisms of cholestatic pruritus: A review","volume":"1866","author":"Sanjel","year":"2020","journal-title":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},{"issue":"10","key":"10.3233\/JND-210712_ref17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0960-8966(02)00153-0","article-title":"Genotype-phenotype correlations in X-linked myotubular myopathy","volume":"12","author":"McEntagart","year":"2002","journal-title":"Neuromuscul Disord"},{"issue":"9","key":"10.3233\/JND-210712_ref18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4254\/wjh.v6.i9.632","article-title":"Liver involvement in systemic infection","volume":"6","author":"Minemura","year":"2014","journal-title":"World J Hepatol"},{"issue":"6","key":"10.3233\/JND-210712_ref19","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.clinre.2012.06.006","article-title":"The bile salt export pump (BSEP) in health and disease","volume":"36","author":"Kubitz","year":"2012","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"44","key":"10.3233\/JND-210712_ref20","doi-asserted-by":"crossref","first-page":"18763","DOI":"10.1073\/pnas.0900705106","article-title":"T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase","volume":"106","author":"Al-Qusairi","year":"2009","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"10","key":"10.3233\/JND-210712_ref21","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1073\/pnas.96.10.5814","article-title":"Phosphoinositide 3-kinase lipid products regulate ATP-dependent transport by sister of P-glycoprotein and multidrug resistance associated protein 2 in bile canalicular membrane vesicles","volume":"96","author":"Misra","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7586","key":"10.3233\/JND-210712_ref22","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1038\/nature16516","article-title":"A phosphoinositide conversion mechanism for exit from endosomes","volume":"529","author":"Ketel","year":"2016","journal-title":"Nature"},{"issue":"8","key":"10.3233\/JND-210712_ref23","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1091\/mbc.e08-04-0367","article-title":"Sequential actions of myotubularin lipid phosphatases regulate endosomal PI(3)P and growth factor receptor trafficking","volume":"19","author":"Cao","year":"2008","journal-title":"Mol Biol Cell"},{"issue":"41","key":"10.3233\/JND-210712_ref24","doi-asserted-by":"crossref","first-page":"26638","DOI":"10.1074\/jbc.273.41.26638","article-title":"The role of phosphoinositide 3-kinase in taurocholate-induced trafficking of ATP-dependent canalicular transporters in rat liver","volume":"273","author":"Misra","year":"1998","journal-title":"J Biol Chem"},{"issue":"5","key":"10.3233\/JND-210712_ref25","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jhep.2010.05.015","article-title":"Phosphatidylinositol-3-kinase p110\u03b3 contributes to bile salt-induced apoptosis in primary rat hepatocytes and human hepatoma cells","volume":"53","author":"Hohenester","year":"2010","journal-title":"J Hepatol"},{"issue":"2","key":"10.3233\/JND-210712_ref26","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1152\/physrev.00027.2002","article-title":"Bile salt transporters: Molecular characterization, function, and regulation","volume":"83","author":"Trauner","year":"2003","journal-title":"Physiol Rev"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-210712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:49:53Z","timestamp":1777506593000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-210712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,4]]},"references-count":23,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.3233\/jnd-210712","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,4]]}}}