{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T09:50:28Z","timestamp":1771062628134,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"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":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sitosterolemia is an extremely rare autosomal recessive disease caused by mutations in either <jats:italic>ABCG5<\/jats:italic> or <jats:italic>ABCG8<\/jats:italic>, which encode for a sterol efflux transporter (sterolin) that pumps sterols out into the intestinal lumen or into bile. This leads to progressive accumulation of plant sterols in blood and tissues. Clinical presentation is variable and may include xanthoma, arthritis, thyroid dysfunction, premature atherosclerotic disease, splenomegaly, and hematologic manifestations. We report a child presented with multiple xanthomas at age 5.5\u2009years, located on the elbow, knee, and toe. Juvenile xanthogranuloma was considered based on histopathologic findings. At 8\u2009years of age, a lipid profile showed markedly elevated total cholesterol (9.4\u2009mmol\/L) and low\u2010density lipoprotein cholesterol (LDL\u2010C, 7.4\u2009mmol\/L). Simvastatin therapy was initiated, however, the lipid profile was persistently abnormal. At age 8.5\u2009years, genetic testing identified two novel variants: (NM_022437.3[ABCG8]:c.1444del;p.Leu482Trpfs*40) and (NM_022437.3[ABCG8]:c.1640T&gt;C;p.Leu547Pro) in the <jats:italic>ABCG8<\/jats:italic> gene. Plasma sitosterol was subsequently found to be very high, confirming the diagnosis. She was started on a low plant sterol and cholesterol diet for 6\u2009weeks with insignificant response and therefore ezetimibe (10 mg daily) was added. This resulted in significant reduction of cholesterol, LDL, sitosterol levels, and no further increase in the size of the xanthomas. This case emphasizes the diagnostic odyssey, the benefits of genomic testing and importance of a correct diagnosis in order to initiate appropriate therapy. It also illustrates the importance of considering rare conditions, such as sitosterolemia, as a differential diagnosis in patients with hypercholesterolemia and increased LDL\u2010C.<\/jats:p>","DOI":"10.1002\/jmd2.12161","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T15:07:31Z","timestamp":1597936051000},"page":"34-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dig deeper when it does not make sense: Juvenile xanthomas due to sitosterolemia"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4664-0690","authenticated-orcid":false,"given":"Sharmila","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Metabolic Medicine The Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy Yaplito","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine The Royal Children's Hospital  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Pitt","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duncan","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology The Royal Children's Hospital  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Wallace","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Marty","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services Murdoch Children's Research Institute  Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasha J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services Murdoch Children's Research Institute  Parkville Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"217","volume-title":"Evidence\u2010Based Management of Lipid Disorders","author":"Patel SB","year":"2010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1771"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/321294"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12038"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M400310-JLR200"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2017.04.116"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.05.049"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-014-0424-2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41411-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2014_404"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000149140.00499.92"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200104000-00007"},{"key":"e_1_2_10_14_1","first-page":"15","article-title":"Clinical features and genetic analysis of childhood sitosterolemia","volume":"98","author":"Huang D","year":"2019","journal-title":"Medicine"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-2107C"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.06.003"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2008.01841.x"},{"key":"e_1_2_10_18_1","first-page":"2961","volume-title":"Inborn Errors in Bile Acid Biosynthesis and Storage of Sterols Other than Cholesterol. 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