{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:55:27Z","timestamp":1782932127569,"version":"3.54.5"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysosomal acid lipase deficiency (LALD) varies from a severe infantile-onset form (Wolman disease) to a late-onset form known as cholesteryl ester storage disease (CESD), both of which are autosomal recessive disorders caused by biallelic LIPA pathogenic variants. We evaluated seventy-three patients enlisted for liver transplant (LT) at Instituto da Crian\u00e7a (HCFMUSP\u2014Brazil) who were subjected to LAL activity measurement and LIPA Sanger sequencing analysis, resulting in a positive LALD diagnosis for only one of these individuals. This LALD patient presented recurrent diarrhea, failure to thrive, hepatomegaly, and dyslipidemia at the age of 4 months and liver failure by the age of 13 years. The LALD diagnosis confirmation was conducted at 24 years old due to low levels of LAL enzyme activity. The causal homozygous variant LIPA(NM_000235.4):c.266T&gt;C(p.Leu89Pro) was identified, but the patient had already undergone his first LT at 18 years with several rejection episodes. Despite beginning treatment with sebelipase alfa at 26 years old (total of five infusions), this patient died at 28 years from complications after his second liver transplant. LALD is an important differential diagnosis in cases presenting with hepatomegaly, elevated liver enzymes, and dyslipidemia. Detecting low\/absent LAL activity and identifying the LIPA causal variant are essential for diagnosis and specific treatment, as well as for appropriate genetic counseling. Early diagnosis, along with sebelipase alfa therapy, may improve the prognosis of affected patients.<\/jats:p>","DOI":"10.3390\/ijms25168648","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:04:24Z","timestamp":1723129464000},"page":"8648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of 73 Enlisted Patients for Liver Transplant with Unknown Etiology Reveals a Late-Diagnosed Case of Lysosomal Acid Lipase Deficiency"],"prefix":"10.3390","volume":"25","author":[{"given":"Karina Lucio de Medeiros","family":"Bastos","sequence":"first","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5711-0230","authenticated-orcid":false,"given":"Bruno de Oliveira","family":"Stephan","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-293X","authenticated-orcid":false,"given":"Bianca Domit Werner","family":"Linnenkamp","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa Athayde","family":"Costa","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana Roberto","family":"Lima","sequence":"additional","affiliation":[{"name":"Departamento de Anatomia Patol\u00f3gica, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-010, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5599-2236","authenticated-orcid":false,"given":"Laura Machado Lara","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Centro de Estudos do Genoma Humano e C\u00e9lulas-Tronco, Instituto de Bioci\u00eancias da Universidade de S\u00e3o Paulo (IBUSP), Sao Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel Sayuri","family":"Honjo","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uenis","family":"Tannuri","sequence":"additional","affiliation":[{"name":"Cirurgia Pedi\u00e1trica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Aoun","family":"Tannuri","sequence":"additional","affiliation":[{"name":"Cirurgia Pedi\u00e1trica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-1300","authenticated-orcid":false,"given":"Chong Ae","family":"Kim","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica, Instituto da Crian\u00e7a, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo (FMUSP), Sao Paulo 05403-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.molmed.2023.03.001","article-title":"Recent insights into lysosomal acid lipase deficiency","volume":"29","author":"Korbelius","year":"2023","journal-title":"Trends Mol. 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