{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:42:32Z","timestamp":1790260952942,"version":"4.1.0"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2021-0018_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Childhood osteoporosis is often a consequence of a chronic disease or its treatment. Lysinuric protein intolerance (LPI), a rare secondary cause of the osteoporosis, is an autosomal recessive disorder with clinical features ranging from minimal protein intolerance to severe multisystemic involvement. We report a case diagnosed to have LPI using a Next Generation Sequencing (NGS) panel and evaluate the utility of reverse phenotyping.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0018_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>A fifteen-year-old-boy with an initial diagnosis of osteogenesis imperfecta, was referred due to a number of atypical findings accompanying to osteoporosis such as splenomegaly and bicytopenia. A NGS panel (TruSight One Sequencing Panel) was performed and a novel homozygous mutation of c.257G&gt;A (p.Gly86Glu) in the <jats:italic>SLC7A7<\/jats:italic> gene (NM_001126106.2), responsible for LPI, was detected. The diagnosis was confirmed via reverse phenotyping.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0018_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Reverse phenotyping using a multigene panel shortens the diagnostic process.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2021-0018","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T23:40:29Z","timestamp":1617838829000},"page":"957-960","source":"Crossref","is-referenced-by-count":3,"title":["The utility of reverse phenotyping: a case of lysinuric protein intolerance presented with childhood osteoporosis"],"prefix":"10.1515","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0582-8881","authenticated-orcid":false,"given":"Enise","family":"Avci Durmusalioglu","sequence":"first","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Isik","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durdugul","family":"Ayyildiz Emecen","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damla","family":"Goksen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samim","family":"Ozen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin","family":"Onay","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melis","family":"Kose","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir","family":"Atik","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukran","family":"Darcan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetes, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozgur","family":"Cogulu","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferda","family":"Ozkinay","sequence":"additional","affiliation":[{"name":"Pediatric Genetics Subdivision, Department of Pediatrics, Faculty of Medicine , Ege University , Izmir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,4,7]]},"reference":[{"key":"2023040101233466001_j_jpem-2021-0018_ref_001","doi-asserted-by":"crossref","unstructured":"Marrani, E, Giani, T, Simonini, G, Cimaz, R. Pediatric osteoporosis: diagnosis and treatment considerations. Drugs 2017;77:679\u201395. Epub 2017\/03\/09. https:\/\/doi.org\/10.1007\/s40265-017-0715-3.","DOI":"10.1007\/s40265-017-0715-3"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_002","doi-asserted-by":"crossref","unstructured":"Torrents, D, Mykk\u00e4nen, J, Pineda, M, Feliubadal\u00f3, L, Est\u00e9vez, R, de Cid, R, et al.. Identification of SLC7A7, encoding y + LAT-1, as the lysinuric protein intolerance gene. Nat Genet 1999;21:293\u20136. https:\/\/doi.org\/10.1038\/6809.","DOI":"10.1038\/6809"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_003","doi-asserted-by":"crossref","unstructured":"Sebastio, G, Sperandeo, MP, Andria, G. Lysinuric protein intolerance: reviewing concepts on a multisystem disease. Am J Med Genet C Semin Med Genet 2011;157:54\u201362. https:\/\/doi.org\/10.1002\/ajmg.c.30287.","DOI":"10.1002\/ajmg.c.30287"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_004","doi-asserted-by":"crossref","unstructured":"Lindahl, K, Astrom, E, Rubin, CJ, Grigelioniene, G, Malmgren, B, Ljunggren, O, et al.. Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta. Eur J Hum Genet 2015;23:1112. https:\/\/doi.org\/10.1038\/ejhg.2015.129.","DOI":"10.1038\/ejhg.2015.129"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_005","doi-asserted-by":"crossref","unstructured":"Mauhin, W, Habarou, F, Gobin, S, Servais, A, Brassier, A, Grisel, C, et al.. Update on lysinuric protein intolerance, a multi-faceted disease retrospective cohort analysis from birth to adulthood. Orphanet J Rare Dis 2017;5:3. https:\/\/doi.org\/10.1186\/s13023-016-0550-8.","DOI":"10.1186\/s13023-016-0550-8"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_006","doi-asserted-by":"crossref","unstructured":"Ogier de Baulny, H, Schiff, M, Dionisi-Vici, C. Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder. Mol Genet Metabol 2012;106:12\u20137. https:\/\/doi.org\/10.1016\/j.ymgme.2012.02.010.","DOI":"10.1016\/j.ymgme.2012.02.010"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_007","doi-asserted-by":"crossref","unstructured":"Carpenter, TO, Levy, HE, Holtrop, ME, Shih, VE, Anast, CE. Lysinuric protein intolerance presenting as childhood osteoporosis. Clinical and skeletal response to citrulline therapy. N Engl J Med 1985;312:290\u20134. https:\/\/doi.org\/10.1056\/nejm198501313120506.","DOI":"10.1056\/NEJM198501313120506"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_008","doi-asserted-by":"crossref","unstructured":"Posey, JE, Burrage, LC, Miller, MJ, Liu, P, Hardison, MT, Elsea, SH, et al.. Lysinuric protein intolerance presenting with multiple fractures. Mol Genet Metabol Rep 2014;1:176\u201383. https:\/\/doi.org\/10.1016\/j.ymgmr.2014.03.004.","DOI":"10.1016\/j.ymgmr.2014.03.004"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_009","doi-asserted-by":"crossref","unstructured":"Guzel-Ozanturk, A, Ozgul, RK, Unal, O, Hismi, B, Ayd\u0131n, H\u0130, Sivri, S, et al.. Molecular and clinical evaluation of Turkish patients with lysinuric protein intolerance. Gene 2013;521:293\u20135. https:\/\/doi.org\/10.1016\/j.gene.2013.03.033.","DOI":"10.1016\/j.gene.2013.03.033"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_010","doi-asserted-by":"crossref","unstructured":"Svedstrom, E, Parto, K, Marttinen, M, Virtama, P, Simell, O. Skeletal manifestations of lysinuric protein intolerance. A follow-up study of 29 patients. Skeletal Radiol 1993;22:11\u20136. https:\/\/doi.org\/10.1007\/BF00191519.","DOI":"10.1007\/BF00191519"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_011","doi-asserted-by":"crossref","unstructured":"Parto, K, Penttinen, R, Paronen, I, Pelliniemi, L, Simell, O. Osteoporosis in lysinuric protein intolerance. J Inherit Metab Dis 1993;16:441\u201350. https:\/\/doi.org\/10.1007\/bf00710296.","DOI":"10.1007\/BF00710296"},{"key":"2023040101233466001_j_jpem-2021-0018_ref_012","doi-asserted-by":"crossref","unstructured":"Habib, A, Md Yunus, Z, Azize, NA, Ch\u2019ng, GS, Ong, WP, Chen, BC, et al.. Hyperexcretion of homocitrulline in a Malaysian patient with\u00a0lysinuric protein intolerance. Eur J Pediatr 2013;172:1277\u201381. https:\/\/doi.org\/10.1007\/s00431-013-1947-1.","DOI":"10.1007\/s00431-013-1947-1"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2021-0018\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2021-0018\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T19:56:49Z","timestamp":1680379009000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2021-0018\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,7]]},"references-count":12,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4,19]]},"published-print":{"date-parts":[[2021,7,27]]}},"alternative-id":["10.1515\/jpem-2021-0018"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2021-0018","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,7]]}}}