Cystinosis as a lysosomal storage disease with multiple mutant alleles: Phenotypic-genotypic correlations.

Cystinosis is an autosomal recessive lysosomal storage disease with an unclear enzymatic defect causing lysosomal cystine accumulation with no corresponding elevation of plasma cystine levels leading to multisystemic dysfunction. The systemic manifestations include a proximal renal tubular defect (Fanconi-like), endocrinal disturbances, eye involvements, with corneal, conjunctival and retinal depositions, and neurological manifestations in the form of brain and muscle dysfunction. Most of the long-term ill effects of cystinosis are observed particularly in patients with long survival as a result of a renal transplant. Its responsible CTNS gene that encodes the lysosomal cystine carrier protein (cystinosin) has been mapped on the short arm of chromosome 17 (Ch17 p13). There are three clinical forms based on the onset of main symptoms: nephropathic infantile form, nephropathic juvenile form and non-nephropathic adult form with predominant ocular manifestations. Avoidance of eye damage from sun exposure, use of cystine chelators (cysteamine) and finally renal transplantation are the main treatment lines. Pre-implantation genetic diagnosis for carrier parents is pivotal in the prevention of recurrence.