What are the other Names for this Condition? (Also known as/Symptoms)

• Cistinuria
• Cystine-Lysine-Arginine-Ornithinuria
• Cystinuria with Dibasic Aminoaciduria

What is Cystinuria? (Definition/Background Information)

• Cystinuria is a genetic disorder that is known to commonly affect individuals between the ages of 10 and 30 years. It is inherited in an autosomal recessive manner, which means that an individual must have two defective copies of a causative gene for manifestation of the condition
• Cystinuria is caused by mutation(s) in either the SLC3A1 or the SLC7A9 genes. In unaffected individuals, both of the genes code for protein subunits involved in reabsorption of certain amino acids from liquid waste, before it becomes urine
• When there is a mutation in either gene, both the assembly and function of the protein complex are affected. The amino acids are not reabsorbed and are instead passed into the urine. While amino acids, such as lysine and arginine, are soluble, cystine tends to form crystals that eventually become stones
• The build-up of cystine and its crystallization in the kidneys, urinary tubes, and urinary bladder leads to the signs and symptoms of Cystinuria. The characteristic symptoms of Cystinuria include pain at many locations including in the lower back, abdomen, flank, and upper back
• Other symptoms can include pain during urination, presence of blood in urine, stones in the kidneys, ureters and bladder, obstruction of urine flow, and frequent urinary tract infections
• Recurrent kidney stones and frequent urinary tract infections are some of the complications associated with Cystinuria. Though end-stage renal disease may occur, it is reported to be rare with this condition
• A diagnosis of Cystinuria is made through a physical examination, assessment of symptoms, evaluation of family medical history, urine tests, and imaging studies of the abdomen
• Treatment options for Cystinuria focus on reducing the acidity of urine through medication and/or diet changes. These changes can include reduction of salt in the diet, taking medication to make cystine more soluble, procedures to breakdown kidney stones, and surgery to remove the stones
• Stone occurrence and recurrence can be prevented by implementation of suitable medication and dietary changes, as well as through regular follow-up examinations
• The prognosis for recurrence-free survival for 1 year stands at approximately 73% and for 5 years at 27%. Cystinuria is considered to be manageable with adequate treatment

Who gets Cystinuria? (Age and Sex Distribution)

• Cystinuria is a rare genetic disorder. The affected population is generally between 10-30 years of age, although some infants may also demonstrate signs of the disorder
• It can affect both males and females
• No specific racial or ethnic group affiliation is observed
• Although the prevalence may vary from country to country, the average rate of occurrence is reported to be 1 in every 10,000 individuals

What are the Risk Factors for Cystinuria? (Predisposing Factors)

• Cystinuria is an inherited condition, and so, having a family history of the disorder is a major risk factor for being diagnosed with the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Cystinuria? (Etiology)

• Cystinuria is caused by mutations the SLC3A1 or SLC7A9 genes
  • Both SLC3A1 and SLC7A9 code for proteins that are subunits of a protein complex chiefly present in the kidneys
  • This protein complex is necessary for reabsorption of amino acids (particularly cystine, which is an oxidized dimer of the amino acid cystine) from the liquid waste that will eventually become urine
  • When there is a mutation in either gene, one subunit of the protein complex becomes faulty, compromising its ability to reabsorb cystine from the liquid waste
  • This leads to an aggregation of cystine in the urine forming crystals or stones, which leads to the classic symptoms of Cystinuria
  • Although other amino acids (lysine, arginine, and ornithine) may not be reabsorbed, they are not reported to form crystal structures like cystine
• The disorder is inherited in an autosomal recessive pattern

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Cystinuria?

The generally reported signs and symptoms of Cystinuria include:

• Sharp pain in the lower back (known as renal colic)
• Blood in urine (hematuria)
• Blockage of renal tubes (ureters)
• Urinary tract infections (the stones offer a surface for bacteria to adhere and grow)
• Pyelonephritis (kidney inflammation as a consequence of bacterial infection)
• Kidney stones, either consisting of cystine alone, or in combination with calcium to form large stones
• Severe pain on one side, which may worsen over the next several days
• Lower back pain; pain in the genital area
• Abdominal discomfort and pain

Note: The type and severity of symptoms may vary among affected individuals

How is Cystinuria Diagnosed?

The diagnosis of Cystinuria may be made through the following tests and exams:

• Complete physical examination with symptom assessment
• An evaluation of family medical history
• Urine tests to check for cystine crystals
• 24-hour urine collection to check for kidney function
• Imaging studies of the abdomen using computed tomography CT), magnetic resonance imaging (MRI) or ultrasound scans
• An X-ray test of the kidneys and urinary tract (intravenous pyelogram)
• Genetic testing, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Cystinuria?

Some potential complications of Cystinuria include:

• Repeated stone formation in the kidneys
• Kidney dysfunction and or failure; end-stage renal disease
• Injury to the urinary bladder
• Obstruction of ureters
• Frequent urinary tract infections
• Severe neurological signs and symptoms

How is Cystinuria Treated?

Cystinuria is not a curable condition. The treatment for the disorder aims to offer relief to patients from symptoms, as well as to prevent recurrent stone formation. Some treatment methods include:

• Increasing fluids intake to at least 6 to 8 glasses per day; if necessary, fluids may be  given intravenously
• Medication to address the pain caused during passing of reasonably large-sized stones in urine
• Extracorporeal shock wave lithotripsy (ESWL) to agitate stones and break them into small pieces, so they will pass through urine
• Procedures, known as percutaneous nephrostolithotomy (nephrolithotomy) and ureteroscopy, to observe stones while they are being broken to small pieces in the kidneys and urinary tract respectively
• Medication, such as potassium citrate and acetazolamide, to increase decrease acidity and alkalinity of urine. Increased alkalinity is reported to make cystine more soluble and may prevent crystallization
• Diet changes to reduce salt intake, in order to reduce crystals formation and include vegetables that decrease urine acidity
• d-penicillamine treatment to change formation of cystine formation to a more soluble form
• Drugs containing alpha-mercaptopropionyl glycine, which is shown to reduce the amounts of cystine in urine
• Angiotensin converting enzyme (ACE) inhibitors may prescribed, which is reported to make cystine more soluble
• Endoscopic basket extraction of stones, where an optic instrument is used to view the stones, and remove them with precision equipment
• Surgery in the kidney or bladder to remove the stones

How can Cystinuria be Prevented?

• Currently, there are no specific methods or guidelines to prevent Cystinuria, since it is a genetic condition
• Genetic testing of expecting parents (and related family members) as well as prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks prior to planning for a child

However, the occurrence of stones in Cystinuria may be prevented by the following measures:

• Screening for genetic susceptibility to Cystinuria, so that essential steps may be taken to prevent cystine crystals and stone formation
• Increased fluids intake
• Including vegetables in the diet to increase alkalinity of urine
• Decreasing salt intake
• Medication to increase alkalinity of urine
• Educating the patients to follow-through with dietary restrictions and medication
• Educating patients to check the pH of their urine, so they can adjust medicine or diet on their own, per his/her healthcare professional’s advice
• Mandatory regular follow-up, since the stones tend to recur

Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Cystinuria.

What is the Prognosis of Cystinuria? (Outcomes/Resolutions)

• The prognosis of Cystinuria depends upon the interval between recurrence of stones, which may affect the quality of life. The condition is chronic and life-long, but generally manageable
• With proper diet, medication, and follow-up care, the kidney stone recurrence-free survival is reported to be approximately 73% for one-year, and 27% for five years

Additional and Relevant Useful Information for Cystinuria:

Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information:

https://www.dovemed.com/diseases-conditions/congenital-genetic-disorders/