{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:06:10Z","timestamp":1792674370888,"version":"4.5.0"},"reference-count":20,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      Lysosomal acid lipase deficiency (LAL\u2010D) is a rare, autosomal recessive disease involving lysosomal accumulation of cholesteryl esters and triglycerides. The International Lysosomal Acid Lipase Deficiency Registry (NCT01633489), established in 2013 to understand LAL\u2010D natural history and long\u2010term outcomes, is accessible to centres caring for patients diagnosed by deficient LAL activity and\/or biallelic pathogenic\n                      <jats:italic>LIPA<\/jats:italic>\n                      variants. We describe the registry population enrolled through 2 May 2022.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective observational study, we analysed demographic and baseline clinical characteristics of children (ages \u22656\u2009months to &lt;18\u2009years) and adults diagnosed with LAL\u2010D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 228 patients with confirmed disease, 61% were children; 202\/220 (92%) with data on race were white. Median age was 5.5\u2009years at sign\/symptom onset and 10.5\u2009years at diagnosis; median time from sign\/symptom onset to diagnostic testing was 3.3\u2009years. The most common manifestations raising suspicion of disease were elevated alanine (70%) and aspartate aminotransferase levels (67%) and hepatomegaly (63%). Among 157 with reported\n                      <jats:italic>LIPA<\/jats:italic>\n                      mutations, 70 were homozygous and 45 were compound heterozygous for the common exon 8 splice junction pathogenic variant (E8SJM\u20101). Seventy percent (159\/228) of patients had dyslipidaemia. Among 118 with liver biopsies, 63% had microvesicular steatosis exclusively, 23% had mixed micro\u2010 and macrovesicular steatosis and 47% had lobular inflammation. Of 78 patients with fibrosis\u2010stage data, 37% had bridging fibrosis and 14% had cirrhosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although LAL\u2010D signs\/symptoms occur early, diagnosis is often delayed. Abnormal transaminase levels associated with hepatomegaly and dyslipidaemia should raise suspicion and prompt earlier diagnosis of LAL\u2010D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>NCT01633489.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15620","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T06:44:54Z","timestamp":1684910694000},"page":"1537-1547","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8047-5011","authenticated-orcid":false,"given":"Manisha","family":"Balwani","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Balistreri","sequence":"additional","affiliation":[{"name":"UC Department of Pediatrics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-3148","authenticated-orcid":false,"given":"Lorenzo","family":"D'Antiga","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation Hospital Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Evans","sequence":"additional","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Ros","sequence":"additional","affiliation":[{"name":"Endocrinology &amp; Nutrition Service Hospital Clinic de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Abel","sequence":"additional","affiliation":[{"name":"Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Endocrinology Cook Children's Medical Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"Grabowski GA","year":"2019"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501365"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.04.003"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23837"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.108"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.014"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000935"},{"key":"e_1_2_11_9_1","unstructured":"Kanuma\u00ae (sebelipase alfa) [package insert]. Alexion Pharmaceuticals Inc.2021."},{"key":"e_1_2_11_10_1","unstructured":"Kanuma\u00ae (sebelipase alfa) [summary of product characteristics]. Levallois\u2010Perret France Alexion Europe.2020."},{"key":"e_1_2_11_11_1","unstructured":"Kanuma\u00ae Japan [package insert]. Alexion Pharma Godo Kaisha.2016."},{"key":"e_1_2_11_12_1","unstructured":"Kanuma\u00ae Canada [Product Monograph]. Alexion Pharma GmbH.2017."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.06.022"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14603"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26289"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-1328-6"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.11.053"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.09.023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medcli.2016.12.044"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2016.11.002"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2019.11.004"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15620","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T08:50:41Z","timestamp":1702025441000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":20,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/liv.15620"],"URL":"https:\/\/doi.org\/10.1111\/liv.15620","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]},"assertion":[{"value":"2022-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}