TY - JOUR
T1 - The Pitfall of White Blood Cell Cystine Measurement to Diagnose Juvenile Cystinosis
AU - Bondue, Tjessa
AU - Kouraich, Anas
AU - Berlingerio, Sante Princiero
AU - Veys, Koenraad
AU - Marie, Sandrine
AU - Alsaad, Khaled O.
AU - Al-Sabban, Essam
AU - Levtchenko, Elena
AU - van den Heuvel, Lambertus
N1 - Funding Information: Tjessa Bondue is funded by Fonds Wetenschappelijk Onderzoek (FWO, Brussels, BE)—11A7823N. Elena Levtchenko is funded by Fonds Wetenschappelijk Onderzoek (FWO, Brussels, BE)—1801120N. Publisher Copyright: © 2023 by the authors.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - cysteamine
KW - cystine
KW - cystinosis
KW - nephropathic cystinosis
UR - http://www.scopus.com/inward/record.url?scp=85146793422&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/ijms24021253
DO - https://doi.org/10.3390/ijms24021253
M3 - Article
C2 - 36674769
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 2
M1 - 1253
ER -