Cystinuria (NORD)

Cystinuria is an inherited metabolic disorder named because of high levels of the amino acid cystine found in urine. The chemically similar amino acids, arginine, lysine and ornithine are also found in high levels.

The kidneys are two bean shaped organs in the body that filter out waste products and excess water from blood to produce urine.

Typically, amino acids are recovered from urine and reabsorbed into the blood by the kidneys. But in cystinuria, impaired reabsorption of cystine arginine lysine and ornithine leads to excessive amounts in urine at high concentration, cystine clumps together to form crystals and stones also called calculi.

These can be found along the urinary tract including the kidneys, ureters and urinary bladder. While high levels of cystine arginine lysine and ornithine in the urine are characteristics of the disorder.

The main signs and symptoms are caused only by the cystine crystals and stones as they stick together and grow larger, they form lemon yellow stones, stones are jagged and can cause sharp pains in the sides and lower back that can radiate to the lower abdomen and groin when they cause obstruction of the ureters.

The pain can come in waves and may be present when urinating stones can also cause injury to tissues in the urinary tract which can lead to blood in the urine.

Frequent recurrences may ultimately lead to lasting kidney damage depending on their size. Stones may obstruct the urinary tract and slow or stop the flow of urine.

This can lead to additional complications like urinary tract infections. Some individuals won't form stones but others typically begin having these symptoms between 10 and 30 years old with a normal ph of urine.

High levels of arginine, lysine and ornithine can be excreted in massive amounts without additional complications. But high levels of cystine are not as soluble and need urine with a higher Ph to completely dissolve undissolved cystine clumps together to form crystals and stones and clumping is more likely when urine volume is low as cystine becomes more concentrated.

Cystinuria is an inherited disorder caused by changes or mutations in either the SLC three A one or SLC seven A nine gene.

These mutations impair the normal reabsorption of cystine, arginine lysine and ornithine cystinuria is an autosomal recessive disorder, which means an individual needs to inherit a mutated copy of the SLC three A one or SLC seven A nine gene from each parent to be affected.

If an individual inherits one mutated and one normal copy, they are considered carriers for the disorder. Carriers usually have minimal to no signs and symptoms of cystinuria.

A few people seem to make stones with only one abnormal SL C seven A nine gene. A diagnosis is typically made based on finding stones in an individual's urinary tract that are made completely of cystine.

So individuals who develop stones are usually screened for cystinuria. Genetic testing for mutations in the SLC three A one and SLC seven A nine genes is available at medical centers that specialize in kidney stone disease but is not necessary to confirm the diagnosis.

Treatment is based on stone prevention by lowering the concentration of cystine dietary modifications like restricting the intake of salt and animal proteins can help reduce the amount of cystine in urine.

Drinking large amounts of fluid throughout the day can minimize clumping, restricting animal protein intake also makes the urine more alkaline helping to dissolve cystine.

Some medications can also make urine more alkaline like potassium citrate and acetaZOLAMIDE and others can make cystine more soluble like alpha mercaptopropionyl glycine, which is also called tiopronin or thiola and the lesser used D penicillAMINE.

But if small stones form drinking large amounts of water and managing pain may be enough to naturally pass them out of the urinary tract.

Larger stones that can't pass on their own may require intervention by a urologist, especially if they are obstructing urine flow surgery may be needed to physically remove them or laser techniques may be used to break them into smaller pieces.

Finally, genetic counseling is recommended for patients and their families to help them understand the genetics and natural history of cystinuria and to provide psychosocial support.

As a quick recap cystinuria is an inherited metabolic disorder caused by mutations in either the SLC three A one or SLC seven A nine genes.

Impaired reabsorption of cystine arginine, lysine and ornithine lead to their high levels in the urine throughout the urinary tract, undissolved cystine can clump together and form crystals and stones.

These cause the main signs and symptoms of the disorder. Diagnosis is based on confirmed 100% cystine stones in urine.

And treatment mostly focuses on stone prevention by lowering the concentration of cystine, increasing its solubility by increasing urine ph and using drugs like tiopronin to keep cystine soluble.