{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:14:09Z","timestamp":1788156849404,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Case Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alpha\u2010mannosidosis is a rare lysosomal storage disease caused by a deficiency of the enzyme alpha\u2010mannosidase. It manifests as a continuous spectrum of signs and symptoms characterized by dysmorphic features, skeletal abnormalities, delayed psychomotor and speech development, impaired hearing, and psychiatric involvement. When suspected, alpha\u2010mannosidosis must be confirmed by biochemical and molecular testing, namely, assessment of blood levels of alpha\u2010mannosidase in leukocytes or fibroblasts and Sanger or next\u2010generation sequencing of the\n                    <jats:italic>MAN2B1<\/jats:italic>\n                    gene. The disease must be diagnosed and treatment started as quickly as possible, since the long\u2010term prognosis for untreated patients is very poor. Enzyme replacement therapy (ERT, human recombinant alpha\u2010mannosidase) has replaced allogeneic stem cell transplant as the mainstay of therapy, thus improving disease\u2010related outcomes with, for example, reduced serum oligosaccharide levels, greater functional capacity, and improved quality of life, all with a good safety profile. We report the seventh case of alpha\u2010mannosidosis in Spain. The patient was a 3.5\u2010year\u2010old girl assessed in the clinical genetics department for developmental delay and marked dysmorphic features (trigonocephaly, exophthalmos, hypertelorism, and a flat nasal bridge). Radiography revealed shortening and thickening of the long bones, as well as metopic and coronal synostosis. Craniosynostosis was treated with surgery. Assessment of alpha\u2010mannosidase revealed complete absence of enzymatic activity. Genetic analysis revealed the homozygous pathogenic variant of\n                    <jats:italic>MAN2B1<\/jats:italic>\n                    , c.2248C&gt;T, which is associated with alpha\u2010mannosidosis. ERT is the only currently available pharmacological option for treating children with mild\u2010to\u2010moderate alpha\u2010mannosidosis. Without ERT, patients' quality of life would be impaired, and their prognosis would worsen significantly.\n                  <\/jats:p>","DOI":"10.1002\/ccr3.73276","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T11:04:35Z","timestamp":1785841475000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alpha\u2010Mannosidosis in a 3.5\u2010Year\u2010Old Girl: A Case Report"],"prefix":"10.1002","volume":"14","author":[{"given":"Samuel","family":"Bonilla Fornes","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hospital Materno Infantil, SES  Badajoz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pilar","family":"Mendez Perez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Materno Infantil, SES, School of Medicine University of Extremadura  Badajoz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Torres Diaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Materno Infantil, SES, School of Medicine University of Extremadura  Badajoz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Sanchez Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Genetics and Immunology Hospital Universitario de Badajoz  Badajoz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-8230","authenticated-orcid":false,"given":"Enrique","family":"Gal\u00e1n G\u00f3mez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Materno Infantil, SES, School of Medicine University of Extremadura  Badajoz Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.01.024"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12138"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61273"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.04.003"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010018\u20100175\u20102"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010013\u20109622\u20102"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24864"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010020\u201001574\u2010w"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.11.008"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes16080915"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.04.001"},{"key":"e_1_2_13_13_1","unstructured":"European Medicines Agency (EMA) \u201cEuropean Public Assessment Report Lamzede \u201d2018 https:\/\/www.ema.europa.eu\/en\/documents\/assessment\u2010report\/lamzede\u2010epar\u2010public\u2010assessment\u2010report_en.pdf."},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-018-0185-0"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2011.99"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001549\u20108"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-013-9595-1"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12602"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/2326409818796854"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2021.100826"}],"container-title":["Clinical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.73276","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ccr3.73276","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ccr3.73276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:22:08Z","timestamp":1788153728000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ccr3.73276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":19,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ccr3.73276"],"URL":"https:\/\/doi.org\/10.1002\/ccr3.73276","archive":["Portico"],"relation":{},"ISSN":["2050-0904","2050-0904"],"issn-type":[{"value":"2050-0904","type":"print"},{"value":"2050-0904","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2025-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e73276"}}