Nephropathic cystinosis in a Chilean cohort: Clinical and genetic characterization

Abstract Cystinosis is a rare disease caused by CTNS gene defects. The main clinical presentations are nephropathic infantile cystinosis (NIC) and nephropathic juvenile cystinosis (NJC); both develop chronic kidney disease (CKD) and extrarenal complications. Opportune diagnosis and access to therapy are challenging in developing countries. Objectives: To describe the clinical and genetic profile of all cystinosis patients diagnosed in Chile. Methods: We performed a retrospective review of the clinical records of cystinosis patients diagnosed from 1994 to 2022. Age at diagnosis, glomerular filtration rate, metabolic variables, anthropometric values, treatment, genetics analysis and outcomes were recorded. Results: Nine patients (8NIC/1NJC) were diagnosed. Patients with NIC had a median age of 16.5 (IQR 13-23) months at diagnosis, and two patients died during follow-up. Most patients started cysteamine therapy within 5 months after diagnosis and reached CKD stages 3-4 within four years. Laboratory and clinical evaluations improved after CKD management and cysteamine therapy. During the follow-ups, all but one of the NIC patients showed height for age Z-score values between -1.5 and -4.0. Two patients received kidney transplantation, and one of them still remains functional after 15 years. The single NJC was a 21-year-old female patient who received insufficient cysteamine and rapidly reached CKD stage 4. Genetic testing was positive in 7/7 cases, with del57kb being the predominant variant (10/14 alleles). Conclusion: Developing countries still face many challenges in providing adequate healthcare to cystinosis patients. Opportune genetic testing may facilitate early diagnosis, resulting in better prognoses.