{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:47:31Z","timestamp":1788292051788,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aspartylglucosaminuria (AGU) (OMIM #208400) is a recessively inherited disorder of glycoprotein catabolism, a subset of the lysosomal storage disorders (LSDs). Deficiency of the enzyme <jats:italic>glycosylasparaginase<\/jats:italic> (E.C. 3.5.1.26) leads to accumulation of aspartylglucosamine in various organs and its excretion in the urine. The disease is characterized by an initial period of normal development in infancy, a plateau in childhood, and subsequent regression in adolescence and adulthood. No curative treatments are currently available, leading to a protracted period of significant disability prior to early death. Hematopoietic stem cell transplantation (HSCT) has demonstrated efficacy in other LSDs, by providing enzyme replacement therapy in somatic viscera and decreasing substrate accumulation. Moreover, donor\u2010derived monocytes cross the blood\u2010brain barrier, differentiate into microglia, and secrete enzyme in the central nervous system (CNS). This has been shown to improve neurocognitive outcomes in other LSDs. The evidence to date for HSCT in AGU is varied, with marked improvement in glycosylasparaginase enzyme activity in the CNS in mice models, but varying neurocognitive outcomes in humans. We present a case series of four children with AGU who underwent HSCT at different ages (9\u2009years, 5\u2009years, 5\u2009months, and 7\u2009months of age), with long\u2010term follow\u2010up post\u2010transplant (over 10\u2009years). These cases demonstrate similar neurodevelopmental heterogeneity based on formal developmental assessments. The third case, transplanted prior to the onset of neurocognitive involvement, is developing normally despite a severe phenotype in other family members. This suggests that further research should examine the role of early HSCT in management of AGU.<\/jats:p>","DOI":"10.1002\/jmd2.12222","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T14:10:16Z","timestamp":1620223816000},"page":"3-11","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effectiveness of early hematopoietic stem cell transplantation in preventing neurocognitive decline in aspartylglucosaminuria: A case series"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3073-2555","authenticated-orcid":false,"given":"Arthavan","family":"Selvanathan","sequence":"first","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Children's Hospital at Westmead Clinical School, the Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Kinsella","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Moore","sequence":"additional","affiliation":[{"name":"NSW Biochemical Genetics Service The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Wynn","sequence":"additional","affiliation":[{"name":"Department of Blood and Marrow Transplant Royal Manchester Children's Hospital  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Jones","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Children's Hospital at Westmead Clinical School, the Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"},{"name":"Blood and Marrow Transplant Service The Children's Hospital at Westmead  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Wilcken","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Children's Hospital at Westmead Clinical School, the Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0518-5879","authenticated-orcid":false,"given":"Kaustuv","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Genetic Metabolic Disorders Service The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Children's Hospital at Westmead Clinical School, the Faculty of Medicine and Health The University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00200902"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(68)92355-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0544-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.7.13.8405810"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2011.1.285"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205858109"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1993.tb12761.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.9.983"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005371802085"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92187-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1993.tb04114.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3928\/00904481-20090723-09"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1296-1375"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9158-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta16390"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)91046-1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0416"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.09.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-472X(99)00075-2"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704665"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)63202-3"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200408150-00015"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2001.110119"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcl.2009.11.004"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474086.2013.816507"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13059"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T21:59:44Z","timestamp":1693346384000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/jmd2.12222"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12222","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"2020-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}