What is Cystinuria?

Cystinuria is a condition characterized by the buildup of the amino acid cystine, a building block of most proteins, in the kidneys and bladder. As the kidneys filter blood to create urine, cystine is normally absorbed back into the bloodstream. People with cystinuria cannot properly reabsorb cystine into their bloodstream, so the amino acid accumulates in their urine.

As urine becomes more concentrated in the kidneys, the excess cystine forms crystals. Larger crystals become stones that may lodge in the kidneys or in the bladder. Sometimes cystine crystals combine with calcium molecules in the kidneys to form large stones. These crystals and stones can create blockages in the urinary tract and reduce the ability of the kidneys to eliminate waste through urine. The stones also provide sites where bacteria may cause infections.

Cystinuria affects approximately 1 in 10,000 people.

Cystine is an amino acid which is a fundamental building block of protein in the body. Cystine and other amino acids are typically recycled within the body as proteins are broken down and rebuilt to support the biochemical processes that enable us to live and grow. Unlike other biochemicals, amino acids are usually reclaimed from the urine during processing in the kidneys, with only small amounts ending up in the final product. However, when cystine is abundant in a person’s urine, that person is said to have cystinuria (literally, “cystine in the urine”).

Mutations in the SLC3A1 or SLC7A9 gene cause cystinuria. The SLC3A1 and SLC7A9 genes provide instructions for making the two parts (subunits) of a protein complex that is primarily found in the kidneys . Normally this protein complex controls the reabsorption of certain amino acids, including cystine, into the blood from the filtered fluid  that will become urine. Mutations in either the SLC3A1 gene or SLC7A9 gene disrupt the ability of the protein complex to reabsorb amino acids , which causes the amino acids to become concentrated in the urine. As the levels of cystine in the urine increase, the crystals typical of cystinuria form. The other amino acids that are reabsorbed by the protein complex do not create crystals when they accumulate in the urine.

Cystinuria is inherited in an autosomal recessive manner. This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. The parents of an affected person usually each carry one mutated copy of the gene and are referred to as carriers. Carriers typically do not show signs or symptoms of the condition. When two carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% chance to not have the condition and not be a carrier.

People with cystinuria are affected with varying degrees of severity. Some may have the disease but no symptoms of stone formation while others will become frequent stone formers. Treatments aside, the mechanisms governing the severity of cystine stone formation among people affected by the disease remain largely unknown and are a topic of active research.