Cystinuria is an inherited health condition that involves the excretion of excess cystine and other dibasic amino acids in the urine. Although cystinuria itself doesn’t cause noticeable symptoms, the increased concentration of cystine puts patients at risk of kidney stone formation, which can lead to severe pain and other related complications.
Cystinuria is inherited in an autosomal recessive pattern, which means that an individual needs to inherit one gene mutation from each parent to be affected by the condition.
For example, if both parents are genetic carriers for the condition, each child will have 25% chance of inheriting no defect and being unaffected, 50% chance of inheriting one defect and being a carrier for the condition, and 25% chance of inheriting two defects and suffering from cystinuria.
There are two main genes associated with causing cystinuria: SLC3A1 and SLC7A9. Mutations in these genes affect the production of a protein complex in the kidneys that usually helps to regulate cystine reabsorption from the urine.
There are three types of cystinuria with the current classification system as follows:
- Type A: mutation in both SLC3A1 alleles, with normal cystine and dibasic amino acid excretion in the urine.
- Type B: mutation in both SLC7A9 alleles, with increased cystine and dibasic amino acid excreted in the urine.
- Type AB: mutation in one SLC3A1 and one SLC7A9 allele, also known as mixed-type cystinuria.
Symptoms and Complications
Most patients with cystinuria present with their first case of kidney stones between 20 and 30 years of age, although some may experience this earlier as an adolescent or child. Symptoms of kidney stones as a result of cystinuria may include:
- Unilateral back pain
- Nausea and vomiting
In addition, some individuals may be affected by psychological symptoms as a secondary effect of the condition. They may suffer from depression due to the chronic nature of the disease and the knowledge that a stone may form at any moment.
There are also complications that may affect patients with cystinuria. These include:
- Renal colic
- Recurrent urinary tract infections
- Kidney damage
The diagnosis of cystinuria involves a consultation of family and medical history complemented by diagnostic tests to confirm the cause.
As cystinuria is a genetic condition, it is important to ask questions about the family history and establish if other family members have been affected by the condition.
Urinalysis is a useful examination of the urine in a laboratory to detect abnormal urine content, in particular the concentration of cystine.
Diagnostic imaging techniques, such as ultrasound and computed tomography (CT) scans can also provide useful insight into the structural changes of the renal system and any calculi (stones) that may be present.
Initial treatment for cystinuria involves lifestyle modifications to prevent the formation of calculi in the kidneys that will result in symptoms. Increasing fluid intake and reducing the consumption of salt are two simple ways to facilitate this.
Pharmacological treatments may be required to help prevent the formation of stones or reduce the size of existing stones. Alkalinising agents help to increase the pH of the urine, which increases the solubility of cystine and enables it to be excreted rather than forming stones. Chelation therapy with D-penicillamine or tiopronin may also help to increase solubility of cystine and reduce symptoms. Alpha-MPG in another type of chelating agent that is also effective but is associated with fewer side effects.
Finally, surgery can also be used to remove large stones and relieve the related symptoms. Extracorporeal shock wave lithotripsy (ESWL) uses shockwaves to fragment large stones into smaller pieces that can pass through the ureters for excretion. Percutaneous nephrolithotomy inserts an instrument into the kidney to break the stones or remove them from the organ entirely. Although surgical procedures can effectively remove stones from the renal system, they do not help to prevent future stones from recurring, so other methods are also required.