Cystinuria

Other Names: CSNU; Cystinuria-lysinuria

Cystinuria is an inherited condition characterized by a buildup of the amino acid , cystine, in the kidneys and bladder. This leads to the formation of cystine crystals and/or stones which may block the urinary tract.

Signs and symptoms

Signs and symptoms of the condition are related to the presence of stones and may include nausea, hematuria, flank pain, and/or frequent urinary tract infections.Chronic or acute renal failure (rare)

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormality of amino acid metabolism
• Hematuria (Blood in urine)
• Nephrolithiasis (Kidney stones)

30%-79% of people have these symptoms

• Hyperuricemia (High blood uric acid level)
• Renal insufficiency (Renal failure)

cause

Cystinuria is caused by changes (mutations) in the ''SLC3A1'' and ''SLC7A9'' genes 

These genes encode a protein complex that helps control the reabsorption of amino acids (such as cystine) in the kidneys. Mutations in these genes disrupt the function of the protein complex, causing cystine to become more concentrated in the urine.

As the concentration of cystine increases, cystine crystals and/or stones begin to form in the urinary tract leading to the many signs and symptoms associated with cystinuria.

Genetics

Autosomal dominant pattern, a 50/50 chance.

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.

Diagnosis

Screening for cystinuria should be considered in people with recurrent or bilateral (i.e. affecting both kidneys) stones; those who develop stones at an early age (before age 30); and people who have a family history of cystinuria. A diagnosis is typically made after an episode of kidney stones when testing reveals that the stones are made of cystine. The following tests may be recommended to detect kidney stones and diagnose cystinuria:

• 24-hour urine collection
• Abdominal imaging  (CT scan,MRI ,or ultrasound )
• Intravenous pyelogram (IVP)
• Urinalysis

Treatment

Treatment of cystinuria is focused on relieving symptoms and preventing the formation of additional stones. A more conservative approach is typically tried first. This may include increasing fluid intake, regular monitoring of urinary pH, dietary restrictions (i.e. eating less salt) and increasing the pH of urine with potassium citrate supplements. If these strategies do not prevent the formation of stones, medications may be added to help dissolve the cystine crystals.

Treatment for cystinuria-related stones varies depending on the size and location of the stone, but may include:

• Extracorporeal shock wave lithotripsy (ESWL)
• Ureteroscopy
• Percutaneous nephrolithotomy
• Open surgery (in rare cases)

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Tiopronin (Brand name: Thiola®)

Prognosis

Cystinuria is a chronic condition and many affected people experience recurrent cystine stones in the urinary tract (kidneys, bladder and ureters). In rare cases, frequent kidney stones can lead to  tissue damage or even kidney failure.

NIH genetic and rare disease info

• NIH info on Cystinuria

Cystinuria is a rare disease.