Phenotypic variability in cystinosis: Lessons from an atypical case

Cystinosis is a rare monogenic autosomal recessive disorder caused by pathogenic variants in the CTNS gene, encoding cystinosin. Loss-of-function of cystinosin leads to intralysosomal cystine accumulation, resulting in cellular dysfunction and multisystem involvement. In addition to symptomatic treatment, early initiation of cysteamine therapy and its strict adherence are essential to delay kidney failure and minimize extrarenal complications. We report the case of a 28-year-old woman diagnosed with infantile cystinosis at two years of age, treated with oral and topical cysteamine since then. Genetic testing identified two CTNS truncating variants associated with the infantile form: c.519_520del p.(Thr173*) and c.18_21del p.(Thr7Phefs*7). Despite a relatively late diagnosis and an unapproved dosing regimen, her leucocyte cystine levels have consistently remained below the upper limit, and both renal and extrarenal manifestations are well-controlled. This case highlights the phenotypic variability of cystinosis and underscores the importance of sustained cysteamine therapy in achieving favorable long-term outcomes, even when initiated later and maintained with an unconventional dosing regimen.