{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T22:39:13Z","timestamp":1785883153521,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T00:00:00Z","timestamp":1561507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["2014\/2020"],"award-info":[{"award-number":["2014\/2020"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alpha\u2010mannosidosis (AM) is a very rare (prevalence: 1\/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi\u2010systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha\u2010mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha\u2010mannosidase in leucocytes and screening for abnormal urinary excretion of mannose\u2010rich oligosaccharides. Genetic confirmation is obtained with the identification of <jats:italic>MAN2B1<\/jats:italic> mutations. Enzyme replacement therapy (LAMZEDE<jats:sup>R<\/jats:sup>) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3\u201323\u2009years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two\u2010sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.<\/jats:p>","DOI":"10.1002\/ajmg.a.61273","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T10:00:26Z","timestamp":1561543226000},"page":"1756-1763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hearing impairment as an early sign of alpha\u2010mannosidosis in children with a mild phenotype: Report of seven new cases"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2193-8685","authenticated-orcid":false,"given":"Daphn\u00e9","family":"Lehalle","sequence":"first","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Colombo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Biochemistry, Faculty of Medicine Catholic University, IRCCS Policlinico Agostino Gemelli  Rome Italy"},{"name":"Center for the Study of Rare Inherited Diseases Niguarda Ca' Granda Metropolitan Hospital  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"O'Grady","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Midland Regional Hospital  Mullingar Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"H\u00e9ron","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence des maladies lysosomales, Service de Neurop\u00e9diatrie H\u00f4pital Armand Trousseau\u2010 La Roche Guyon, APHP  Paris France"},{"name":"GRC N\u00b019, Universit\u00e9 Paris\u2010Sorbonne  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada","family":"Houcinat","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2814-6303","authenticated-orcid":false,"given":"Paul","family":"Kuentz","sequence":"additional","affiliation":[{"name":"FHU TRANSLAD, Centre Hospitalier Universitaire et Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Moutton","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Sorlin","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Thevenon","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Delanne","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Gay","sequence":"additional","affiliation":[{"name":"P\u00e9diatrie, Centre Hospitalier  Chalon\u2010sur\u2010Sa\u00f4ne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Racine","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares 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D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Huet","sequence":"additional","affiliation":[{"name":"Centre de comp\u00e9tence maladies m\u00e9taboliques, H\u00f4pital d'Enfants  Dijon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannis","family":"Duffourd","sequence":"additional","affiliation":[{"name":"FHU TRANSLAD, Centre Hospitalier Universitaire et Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon 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r\u00e9f\u00e9rence des Surdit\u00e9s G\u00e9n\u00e9tiques, Institut Imagine, H\u00f4pital Necker Enfants Malades, APHP  Paris France"},{"name":"INSERM UMR_S1163, IHU Imagine \u2010 Institut des Maladies G\u00e9n\u00e9tiques \u2010 Universit\u00e9 Paris Descartes  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-444X","authenticated-orcid":false,"given":"Laurence","family":"Faivre","sequence":"additional","affiliation":[{"name":"Centre de G\u00e9n\u00e9tique et Centre de R\u00e9f\u00e9rence Maladies Rares \u2018Anomalies du D\u00e9veloppement\u2019 de l'Interr\u00e9gion Est H\u00f4pital d'Enfants, CHU  Dijon France"},{"name":"FHU TRANSLAD, Centre Hospitalier Universitaire et Universit\u00e9 de Bourgogne\u2010Franche Comt\u00e9  Dijon France"},{"name":"Equipe GAD (G\u00e9n\u00e9tique des Anomalies du D\u00e9veloppement), UMR INSERM 1231, Universit\u00e9 de Bourgogne  Dijon 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of alpha\u2010mannosidosis by measuring alpha\u2010mannosidase in plasma","volume":"38","author":"Prence E. M.","year":"1992","journal-title":"Clinical Chemistry"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22005"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22787"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.61273","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61273","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T20:50:46Z","timestamp":1694292646000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61273"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,26]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1002\/ajmg.a.61273"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61273","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,26]]},"assertion":[{"value":"2019-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}