Free lysosomal cystine

Free lysosomal cystine refers to the accumulated form of the disulfide amino acid cystine within the lysosomal compartment, which serves as the primary pathological hallmark of cystinosis. This accumulation is caused by mutations in the CTNS gene, which encodes the lysosomal cystine transporter cystinosin, leading to the failure of cystine export and subsequent crystal formation (Gahl et al., 2002, NEJM). These crystals cause progressive cellular damage and organ dysfunction, most notably in the renal proximal tubules (Fanconi syndrome) and the cornea (Cherqui & Courtoy, 2017, J Inherit Metab Dis). In clinical practice, free lysosomal cystine is the direct chemical target of cysteamine therapy. Cysteamine enters the lysosome and reacts with cystine via a disulfide exchange reaction to produce cysteine and a cysteine-cysteamine mixed disulfide (FDA, 2013, Procysbi Label). This mixed disulfide is then able to exit the lysosome through the PQLC2 transporter, effectively bypassing the defective cystinosin and reducing the toxic cystine burden (Jezegou et al., 2012, Nature). Monitoring the concentration of free lysosomal cystine in white blood cells is the standard method for assessing treatment efficacy and adjusting drug dosage.

Other names

Intralysosomal cystineL-CystineCystine crystals

Cysteamine reacts with lysosomal cystine via a disulfide exchange reaction to form cysteine and a cysteine-cysteamine mixed disulfide, which exits the lysosome via the PQLC2 transporter.