European Cystinosis Cohort 2

Cystinosis is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the CTNS gene encoding cystinosin, the lysosomal cystine transporter. The resulting defect leads to progressive intralysosomal cystine accumulation, causing multisystem cellular dysfunction and progressive organ involvement. The disease typically presents in infancy with renal Fanconi syndrome and progresses to chronic kidney disease and, without cystine-depleting therapy, end-stage kidney disease in childhood. With advances in cysteamine therapy, renal replacement therapy, and kidney transplantation, survival has improved significantly, resulting in a chronic multisystem disease affecting both pediatric and adult populations.

At the cellular level, cystinosis involves lysosomal dysfunction, impaired autophagy, oxidative stress, dysregulated endolysosomal trafficking, and chronic inflammatory activation. Macrophage activation and inflammatory pathways are increasingly recognized as contributors to disease progression.

This study is conducted within the RaDiCo-ECYSCO platform, a European rare disease cohort designed for standardized longitudinal data collection in patients with cystinosis followed in expert reference centers. ECYSCO2 is the continuation of the original ECYSCO cohort and extends long-term follow-up and harmonized clinico-biological data collection.

The cohort is multicentric and includes specialized centers across Europe. It is embedded in routine clinical care, and data collection is non-interventional and based on standard follow-up procedures without modification of patient management.

Data are collected using standardized electronic case report forms (eCRFs) within the REDCap® platform of the RaDiCo information system. The system supports full data lifecycle management including data capture, validation, monitoring, and statistical analysis. Source data are defined as medical records, laboratory reports, imaging data, and patient questionnaires (paper or electronic). Investigators are responsible for ensuring consistency between source documents and eCRF entries.