The
cystine that accumulates within cystinotic lysosomes comes primarily from
proteins which have been degraded within this organelle. The individual
amino acids have specific transport mechanisms to exit the lysosome. The lysosomal
cystine transporter is defective in all types of
cystinosis. When cells from patients with nephropathic and benign
cystinosis were fused, the defect was not corrected and the
cystine level remained elevated. This strongly indicates that the genetic defects are allelic (i.e., on the same chromosome).
Cysteamine is a weak base which enters the cystinotic lysosome and reacts with
cysteamine. forming a mixed
disulfide of
half-cystine and
cysteamine. This mixed
disulfide rapidly exits the lysosome via the transport system for cationic
amino acids which is normal in
cystinosis. Because of the success of
renal transplantation, many
cystinosis patients are alive in their twenties and even early thirties. Unfortunately, these patients have developed damage to other organs including thyroid, eye, central nervous system, pancreas, and muscle.
Cysteamine and its analog,
phosphocysteamine, are very beneficial to
cystinosis patients, especially when started early in life. These drugs may prevent the need for
transplantation. It is too early to know if they will prevent damage to other organs.