The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis

Tjessa Bondue, Anas Kouraich, Sante Princiero Berlingerio, Koenraad Veys, Sandrine Marie, Khaled O. Alsaad, Essam Al-Sabban, Elena Levtchenko, Lambertus van den Heuvel

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 ½ 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 > 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.
Original languageEnglish
Article number1253
JournalInternational journal of molecular sciences
Volume24
Issue number2
DOIs
Publication statusPublished - 1 Jan 2023
Externally publishedYes

Keywords

  • cysteamine
  • cystine
  • cystinosis
  • nephropathic cystinosis

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