Don’t confuse “cystinosis” with “cystinuria”: they are different diseases, both genetic and both involving the amino acid cystine–but with decidedly different pathogeneses.
Hereditary cystinosis is an autosomal recessive disorder caused by mutations in the CTNS gene, which encodes a lysosomal transporter of the amino acid cystine. Without this transporter, cystine accumulates in the lysosomes of proximal tubule cells, eventually leading to cell toxicity. Patients (which typically present in infancy) may have Fanconi’s Syndrome and progressive deterioration of renal disease which usually leads to ESRD. Other identifying clinical characteristics of cystinosis include corneal depositis, hypothyroidism, growth retardation, and hypophosphatemic rickets.
Hereditary cystinuria, on the other hand, is an autosomal recessive condition in which there is a mutation in a dibasic amino acid transporter which is expressed at the apical surface of the tubular lumen. There are two genes, SLC3A1 and SLC7A9, which have been identified thus far. Without the ability to reabsorb basic amino acids, the urine becomes quickly supersaturated with cystine which may precipitate out as pathognomonic hexagonally-shaped crystals (see picture). The main clinical consequence of this phenomenon is an increased susceptibility to stone formation and its resultant complication (e.g., obstruction, pain). Other dibasic amino acids–namely, lysine, arginine, and ornithine–are also found in high concentrations in the urine, but unlike cystine they are freely soluble and do not cause problems.
Thank you so much for writing "Cystinosis vs. Cystinuria." My son has cystinosis and many physicians confuse it with cystinuria. I politely try to explain they are 2 very different diseases. Today, my son was having surgery to remove a kidney stone. As you know kidney stones are not common in cystinosis, but are very common in cystinuria. The physician removing the stone remarked that "it was very interesting that another stone was already quickly forming, but this was to be expected considering his history." I was confused as my son never had a stone until the one that was being removed. Immediately, I thought he must be confusing cystinosis with cystinuria.