{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:03:08Z","timestamp":1788850988174,"version":"build-2803163510"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek (FWO, Brussels, BE)","doi-asserted-by":"publisher","award":["11A7823N"],"award-info":[{"award-number":["11A7823N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek (FWO, Brussels, BE)","doi-asserted-by":"publisher","award":["1801120N"],"award-info":[{"award-number":["1801120N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystinosis is an autosomal recessive lysosomal storage disease, caused by mutations in the CTNS gene, resulting in multi-organ cystine accumulation. Three forms of cystinosis are distinguished: infantile and juvenile nephropathic cystinosis affecting kidneys and other organs such as the eyes, endocrine system, muscles, and brain, and adult ocular cystinosis affecting only the eyes. Currently, elevated white blood cell (WBC) cystine content is the gold standard for the diagnosis of cystinosis. We present a patient with proteinuria at adolescent age and corneal cystine crystals, but only slightly elevated WBC cystine levels (1.31 \u00bd cystine\/mg protein), precluding the diagnosis of nephropathic cystinosis. We demonstrate increased levels of cystine in skin fibroblasts and urine-derived kidney cells (proximal tubular epithelial cells and podocytes), that were higher than the values observed in the WBC and healthy control. CTNS gene analysis shows the presence of a homozygous missense mutation (c.590 A &gt; G; p.Asn177Ser), previously described in the Arab population. Our observation underlines that low WBC cystine levels can be observed in patients with juvenile cystinosis, which may delay the diagnosis and timely administration of cysteamine. In such patients, the diagnosis can be confirmed by cystine measurement in slow-dividing cells and by molecular analysis of the CTNS gene.<\/jats:p>","DOI":"10.3390\/ijms24021253","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T02:09:39Z","timestamp":1673230179000},"page":"1253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1952-6400","authenticated-orcid":false,"given":"Tjessa","family":"Bondue","sequence":"first","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9421-4840","authenticated-orcid":false,"given":"Anas","family":"Kouraich","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-7360","authenticated-orcid":false,"given":"Sante Princiero","family":"Berlingerio","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koenraad","family":"Veys","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"},{"name":"Department of Pediatrics, AZ Delta Campus Torhout, 8820 Torhout, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Marie","sequence":"additional","affiliation":[{"name":"Laboratory of Inherited Metabolic Diseases\/Biochemical Genetics, Cliniques Universitaires Saint-Luc, UC Louvain, 1200 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled O.","family":"Alsaad","sequence":"additional","affiliation":[{"name":"Section of Histopathology, Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Essam","family":"Al-Sabban","sequence":"additional","affiliation":[{"name":"Section of Pediatric Nephrology, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7312","authenticated-orcid":false,"given":"Elena","family":"Levtchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"},{"name":"Department of Pediatrics, University Hospitals Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambertus","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Nephrology, Department of Development and Regeneration, KU Leuven Campus Gasthuisberg, 3000 Leuven, Belgium"},{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Amalia Children\u2019s Hospital, Radboud University Medical Center, HB-6524 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/ng0498-319","article-title":"A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis","volume":"18","author":"Town","year":"1998","journal-title":"Nat. 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