{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:42:27Z","timestamp":1784698947418,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lysosomal acid lipase deficiency (LAL\u2010D) is a multi\u2010organ autosomal recessive disease caused by mutations in <jats:italic>LIPA<\/jats:italic>. We reviewed data from 681 samples (white blood cells [WBC] n\u2009=\u2009625, fibroblasts = 30, liver = 4, amniocytes = 13, chorionic villus = 9) received for analysis of lysosomal acid lipase (LAL) activity over a 15\u2010year period. <jats:italic>LIPA<\/jats:italic> sequencing was performed in 49 patients with reduced (n\u2009=\u200926) or deficient (n\u2009=\u200923) LAL activity. The <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/exac.broadinstitute.org\/about\">Exome Aggregation Consortium and Genome Aggregation Database<\/jats:ext-link> dataset were used for LAL\u2010D prevalence calculations. LAL WBC activity was reduced in 67 patients (10.72%) and deficient in 37 (5.92%). The average of LAL activity \u00b1 margin of error (CI 95%) was 19.32\u2009\u00b1 0.86\u2009pmol\/min\/mg for reduced activity patients and 5.90\u2009\u00b1 1.42\u2009pmol\/min\/mg for deficient patients. The average age at diagnosis for LAL\u2010D was 23.6 years with several patients older than age 30. The correlation between the age at diagnosis and LAL activity showed a significant moderate direct correlation (Pearson's <jats:italic>r<\/jats:italic> = 0.46, <jats:italic>P<\/jats:italic> &lt; 0.005). Homozygous or compound heterozygous mutations were identified in 9 out of 23 patients with deficient results (detection rate 39.1%). The average LAL activity in molecularly confirmed patients was 4.02\u2009\u00b1 2.02\u2009pmol\/min\/mg protein, while in molecularly negative patients was 13.886\u2009\u00b1 1.49\u2009pmol\/min\/mg (<jats:italic>P<\/jats:italic> &lt; 0.0001). Twenty\u2010two different mutations were identified including two novel variants (c.309C&gt;A and c.856G&gt;C). A carrier frequency of approximately 1 in 350 was inferred. LAL activity in WBC is a validated tool for LAL\u2010D diagnosis. Higher residual enzymatic activity might result in a milder phenotype leading to diagnosis delay. A cut\u2010off below 12\u2009pmol\/min\/mg protein might be useful to discriminate patients with <jats:italic>LIPA<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1002\/jimd.12057","type":"journal-article","created":{"date-parts":[[2019,1,26]],"date-time":"2019-01-26T02:44:18Z","timestamp":1548470658000},"page":"509-518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Opening a window on lysosomal acid lipase deficiency: Biochemical, molecular, and epidemiological insights"],"prefix":"10.1002","volume":"42","author":[{"given":"Gerarda","family":"Cappuccio","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Department of Translational Medical Sciences Section of Pediatrics, Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taraka R.","family":"Donti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leroy","family":"Hubert","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Section of Pediatrics, Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1400-8519","authenticated-orcid":false,"given":"Sarah H.","family":"Elsea","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences Section of Pediatrics, Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.12.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.02.014"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.08.021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26327"},{"key":"e_1_2_8_6_1","first-page":"54","article-title":"Acid lipase in cultured fibroblasts: cholesterol ester storage disease","volume":"84","author":"Beaudet AL","year":"1974","journal-title":"J Lab Clin Med"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39900-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116888"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.0162"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39119-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)12:1<44::AID-HUMU7>3.0.CO;2-O"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)31591-1"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i3.1001"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000000175"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2010.0203"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2009.57"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.146639"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.03.019"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.05.027"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_321"},{"key":"e_1_2_8_21_1","unstructured":"GrabowskiG DuH CharnasL(2012) Lysosomal Acid Lipase Deficiencies: The Wolman Disease\/Cholesteryl Ester Storage Disease Spectrum. 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