Cystine is an amino acid, a building block of protein. In the body many different proteins need cystine to give them their specific structure. Cystine is commonly found in the skeleton, connective tissue, hair, skin and nails. The body can make its own supply of cystine from other amino acids. Two cysteine molecules joined together make one cystine molecule.
Proteins are broken down in every cell of the body and the amino acids are mostly recycled. This takes place in a lysosome, a microscopic bag-like structure inside the cell.
In Cystinosis, cystine released inside the lysosome cannot get out into the other parts of the cell. This is because the special transport system in the wall of the lysosome is faulty. As a result cystine builds up in the lysosome. Cystinosis is one of a group of metabolic diseases known as lysosomal storage disorders. Cystine doesn’t dissolve very well in water and forms crystals in the body. This can be seen with a microscope in certain tissues.
Cysteamine, the basic treatment of this condition, dissolves very well in water and gets into the lysosome of the cell. Here it reacts with cystine, splitting the molecule. This produces cysteine (effectively half a cystine molecule) and another soluble product (cysteamine-cysteine disulphide). These do not need the same transport system so the cystine is effectively removed.
The two parts of the body most affected by cystine overload are the kidneys and the eyes. In the kidney the build up of cystine occurs mostly in the cells of the proximal tubule. This is the part of the kidney responsible for reabsorbing large amounts of salt, water and phosphorus. This is why in its early stages Cystinosis is characterised by an excessive loss of fluid and the presence of salt and phosphorus in the urine. This pattern of tubular malfunction is also known as the Renal Fanconi Syndrome. Later on kidneys become extensively damaged and scarred so that overall kidney function is lost.
In the eye, cystine crystals are deposited in several areas including the cornea which is the cause of photophobia. Here the crystals can be seen by examining the eye with a slit lamp.
How is the disease inherited? Cystinosis is a genetic disorder and is inherited.
The gene involved in Cystinosis is called CTNS and it affects a protein called cystinosin. Cystinosin is a transport protein and carries cystine out of the lysosome. We have two copies of this gene, one inherited from each parent. In order for a patient to develop Cystinosis both copies of the gene must be faulty.
Parents of a person with Cystinosis are almost certain to carry one copy of the faulty gene. Because they have a normal copy as well, they are themselves unaffected. One normal copy of CTNS is sufficient to produce enough normal cystinosin for normal cellular function. Parents are therefore carriers of the condition. This pattern of inheritance from unaffected carrier parents to affected child is known as autosomal recessive inheritance.
This diagram shows how Cystinosis can be passed on to the children of two carrier parents.
A = unaffected gene a = affected gene