Cystinuria

Cystinuria is an inherited autosomal recessive disease that is characterized by high concentrations of the amino acid cysteine in the urine, leading to the formation of cystine stones in the kidneys, ureter, and bladder. It is a type of aminoaciduria. Cystinuria is an inherited autosomal recessive disease that is characterized by high concentrations of the amino acid cysteine in the urine, leading to the formation of cystine stones in the kidneys, ureter, and bladder. It is a type of aminoaciduria. Cystinuria is a cause of persistent kidney stones. It is a disease involving the defective transepithelial transport of cystine and dibasic amino acids in the kidney and intestine, and is one of many causes of kidney stones. If not treated properly, the disease could cause serious damage to the kidneys and surrounding organs, and in some rare cases death. The stones may be identified by a positive nitroprusside cyanide test. The crystals are usually hexagonal, translucent, white. Upon removal, the stones may be pink or yellow in color, but later they turn to greenish due to exposure to air. Cystinuria is usually asymptomatic when no stone is formed. However, once a stone is formed, or if stone production is severe or frequent, symptoms may be present: Cystinurics can also experience chronic pain in one, or both, kidneys due to the scars that the jagged edges of the stones can leave or damage from multiple stone removal surgeries. This can leave a cystinuric in constant pain which often requires medical intervention, such as long-term use of analgesics or surgical procedures, including T11, T12 or T13 nerve blocks (although, these procedures are often not successful, they can provide some relief). Aside from the chronic pain, a cystinuric will often have severe breakthrough pain from passing stones. People with cystinuria pass stones monthly, weekly, or daily, and need ongoing care. Cystinurics have an increased risk for chronic kidney disease and since kidney damage or poor function is often present in cystinurics, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) or over the counter (OTC) medications should be used with caution. Cystine stones are often not visible on most x-rays, CT's, and ultrasounds. This does not mean the cystinuric doesn't have a stone. It takes a trained eye and experience to spot a cystine stone. It is not unusual for a cystinuric to pass a stone, or stones, after being released from the hospital with a CT or x-ray result of no stones in the kidneys. Urine odor in cystinuria has a smell of rotten eggs due to the increase in cystine. Cystinuria is an autosomal recessive disease, which means that the defective gene responsible for the disease is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disease. The parents of an individual with an autosomal recessive disease both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disease. Although signs and symptoms are rare, there are some directly and indirectly associated with cystinuria. These sign and symptoms consist of 1) hematuria- blood in the urine, 2) flank pain – pain in the side due to kidney pain, 3) renal colic – intense, cramping pain due to stones in the urinary tract, 4) obstructive uropathy- urinary tract disease due to obstruction, and 5) urinary tract infections. Cystinuria is caused by mutations in the SLC3A1 and SLC7A9 genes. These defects prevent proper reabsorption of basic, or positively charged, amino acids: cysteine, lysine, ornithine, arginine. Under normal circumstances, this protein allows certain amino acids, including cysteine, to be reabsorbed into the blood from the filtered fluid that will become urine. Mutations in either of these genes disrupt the ability of this transporter protein to reabsorb these amino acids, allowing them to become concentrated in the urine. As the levels of cysteine in the urine increase, it forms cystine crystals, resulting in kidney stones. Cystine crystals form hexagonal-shaped crystals that can be viewed upon microscopic analysis of the urine. The other amino acids that are not reabsorbed do not create crystals in urine. The overall prevalence of cystinuria is approximately 1 in 7,000 neonates (from 1 in 2,500 neonates in Libyan Jews to 1 in 100,000 among Swedes). Cystinuria is characterized by the inadequate reabsorption of cystine in the proximal convoluted tubules after the filtering of the amino acids by the kidney's glomeruli, thus resulting in an excessive concentration of this amino acid in the urine. Cystine may precipitate out of the urine, if the urine is neutral or acidic, and form crystals or stones in the kidneys, ureters, or bladder. It is one of several inborn errors of metabolism included in the Garrod's tetrad. The disease is attributed to deficiency in transport and metabolism of amino acids.