Cystinosis - Pathophysiology

Cystinosis is a rare autosomal recessive lysosomal storage disorder affecting 1 in 100,000 – 200,000 live births. It is caused by a mutation in the Cystinosin (CTNS) gene, a cystine-proton cotransporter, the absence of which results in intra-lysosomal accumulation of cystine. Kidneys are affected first, presenting as Fanconi syndrome in infancy, followed by widespread involvement of the eyes, endocrine and neuromuscular system later in life. Cystinosis since being first described in 1903 to the discovery of CTNS gene defect a century later in 1998, has proven to be a complex disease. Clinical features are a manifestation of intra-lysosomal accumulation and interruption of cellular metabolic pathways in the affected organs. In this review, we explore the various pathophysiologic mechanisms underlying the manifestations of this complex disease.