cystinuria(redirected from cystinuria type I)
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Cystinuria is an inborn error of amino acid transport that results in the defective absorption by the kidneys of the amino acid called cystine. The name means "cystine in the urine."
Cystine is an amino acid. Amino acids are organic compounds needed by the body to make proteins and for many normal functions. When the kidneys do not absorb cystine, this compound builds up in the urine. When the amount of cystine in the urine exceeds its solubility (the greatest amount that can be dissolved), crystals form. As the amount of cystine continues to increase in the urine, the number of crystals also increases. When very large numbers of cystine crystals form, they clump together into what is called a stone.
Causes and symptoms
Cystinuria is a rare disease that occurs when people inherit an abnormal gene from their parents. This disease occurs in differing degrees of severity in people who have inherited either one or two abnormal genes. Humans have two copies of each gene. When both are abnormal, the condition is called homozygous for the disease. When one copy is normal and the other is abnormal, the condition is called heterozygous for the disease. Persons with one abnormal gene can have a milder form of cystinuria that rarely results in the formation of stones.
Severe cystinuria occurs when people are homozygous for the disease. For these individuals, the kidneys may excrete as much as 30 times the normal amount of cystine. Research has shown that this condition is caused by mutations on chromosome number two (humans have 23 pairs of chromosomes).
A person who has inherited cystinuria may have other abnormal bodily functions. In addition to excess levels of the amino acid cystine, high amounts of the amino acids lysine, arginine, and ornithine are found in the urine. This condition indicates that these amino acids are not being reabsorbed by the body.
When excess cystine crystals clump together to form a stone, the stone can block portions of the interior of the kidney or the tube (the ureter) that connects the kidney to the urinary bladder. These cystine stones can be painful, and depending upon where the stone becomes trapped, the pain can be felt in the lower back or the abdomen. Nausea and vomiting can also occur, and patients may sometimes feel the need to urinate often. Cystine stones can also cause blood in the urine. When the urinary tract is blocked by a stone, urinary tract infections or kidney failure may result.
Small stones (called "silent") often do not cause any symptoms, although they can be detected by an x ray. Large stones are often painful and easily noticed by the patient. Blood in the urine can also mean that a stone has formed.
When the urine contains extremely high amounts of cystine, yellow-brown hexagonal crystals are visible when a sample is examined under the microscope. Urine samples can also be mixed with chemicals that change color when high levels of cystine are present. When the compound nitroprusside is added to urine that has been made alkaline by the addition of ammonia, the urine specimen turns red if it contains excess cystine.
No treatment can decrease cystine excretion. The best treatment for cystinuria is to prevent stones from forming. Stones can be prevented by drinking enough liquid each day (about 5-7 qts) to produce at least 8 pts of urine, thus keeping the concentration of cystine in the urine low. Because a person does not drink throughout the night, less urine is produced, and the likelihood of stone formation increases. This risk can be minimized by drinking water or other liquids just before going to bed.
In addition to drinking large amounts of fluids, it is helpful to make the urine more alkaline. Cystine dissolves more easily in alkaline urine. To increase urine alkalinity, a person may take sodium bicarbonate and acetazolamide. Penicillamine, a drug that increases the solubility of cystine, may be prescribed for patients who do not respond well to other therapies. This drug must be used with caution, however, because it can cause serious side effects or allergic reactions. For those unable to take penicillamine, another drug, alpha-mercaptopropionylglycine (Thiola), may be prescribed.
Most stones can be removed from the body by normal urination, helped by drinking large amounts of water. Large stones that cannot be passed this way must be removed by surgical procedures.
Large stones can be surgically removed by having a device called a uretoscope placed into the urethra, up through the bladder and into the ureter, where the trapped stone can be seen and removed. Another method involves using sound-wave energy aimed from outside the body to break the large stone into small pieces that can be passed by urination. This external technique is called extracorporeal shock-wave lithotripsy (ESWL).
For large stones in the kidney, a procedure called percutaneous nephrolithomy may be used. In this procedure, the surgeon makes a small incision in the back over the kidney. An instrument called a nephroscope is inserted through the incision into the kidney. The surgeon uses the nephroscope to locate and remove the stone. If the stone is very large, it may be broken up into smaller pieces by an ultrasonic or other kind of probe before removal.
As many as 50% of patients who have had surgical treatment for a kidney stone will have another stone within five years if no medicines are used to treat this condition.
Alkaline — A solution is considered alkaline if it contains fewer hydrogen atoms than pure water.
Amino acid — An organic compound made of an amino group (containing nitrogen and hydrogen) and a carbolic acid group. Amino acids are an essential part of protein molecules.
Nephroscope — An instrument made of a light source in a tube. The tube is inserted into the kidney through an incision in the back and used to locate kidney stones. The stones are broken up with high frequency sound waves and removed by suction through the scope.
Nitroprusside — A compound that is used in laboratory tests to identify large amounts of cystine in urine samples.
Uretoscope — A tube-shaped device inserted into the body through the urinary system that allows objects to be both seen and grasped for removal.
Cystinuria is a genetic disorder that currently cannot be prevented.
Cystinuria Support Network. 21001 NE 36th St., Redmond, WA 98053. (425) 868-2996. http://www.cystinuria.com.
National Kidney Foundation. 30 East 33rd St., New York, NY 10016. (800) 622-9010. http://www.kidney.org.
cys·ti·nu·ri·a(sis'ti-nyū'rē-ă), [MIM*220100, *104614, *600918]
Excessive urinary excretion of cystine, along with lysine, arginine, and ornithine, arising from defective transport systems for these acids in the kidney and intestine; renal function is sometimes compromised by cystine crystalluria and nephrolithiasis. There are at least three forms of cystinuria, which are distinguished by the severity of urinary excretion of cystine in obligate carriers; all with autosomal recessive inheritance. Types I and II cystinuria are allelic disorders caused by mutation in the solute carrier family 3 gene (SLC3A1), which is an amino acid transporter gene on chromosome 2q. Type III is caused by mutation at a separate locus.
[cystine + G. ouron, urine]
cystinuria/cys·tin·uria/ (-ūr´e-ah) a hereditary aminoaciduria with excessive urinary excretion of cystine along with lysine, ornithine, and arginine, due to impaired renal tubular reabsorption.
An inherited disorder characterized by an excess of cystine, lysine, arginine, and ornithine in the urine and often the formation of cystine calculi, caused by impaired reabsorption of these amino acids in the renal tubules.
Etymology: cystine + Gk, ouron, urine
1 abnormal presence of the amino acid cystine in the urine collected in a 24-hour specimen.
2 an inherited defect of the renal tubules, characterized by excessive urinary excretion of cystine and several other amino acids. The disorder is caused by an autosomal-recessive trait that impairs cystine reabsorption by the kidney tubules. In high concentration, cystine tends to precipitate in the urinary tract and form kidney or bladder stones. Treatment attempts to prevent the formation of stones or to dissolve them by increasing the volume of urine flow, decreasing the pH of the urine, and increasing the solubility of cystine. In addition to a large fluid intake, sodium bicarbonate, acetazolamide, and, in refractory cases, d-penicillamine are sometimes prescribed.
cystinuriaAn autosomal disorder (OMIM:220100) characterised by impaired epithelial transport of cystine and dibasic amino acids (lysine, ornithine and arginine) in the proximal renal tubule and gastrointestinal tract, leading to a defect in renal reabsorption of cystine which, given its low solubility, results in the formation of urinary tract calculi, obstructive uropathy, pyelonephritis and, rarely, renal failure.
Cause by defects of:
• SLC3A1, which encodes a glycoprotein involved in the transport of cystine and neutral and dibasic amino acids in the renal tubule and intestinal tract; and
• SLC7A9, which encodes an amino acid transporters that plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids.
cystinuriaMolecular medicine An AR inborn error of metabolism in which there is an ↑ in cystine excretion in urine, with formation of cystine bladder stones 3 forms Based on the amount of cystine excreted; in type I, there is an ↑ urine cystine, ornithine, arginine and lysine; in types II and III, cystine excretion is lower Genetics The variability in expression is attributed to allelism on the genes for each type. Cf Cystinosis.
Excessive urinary excretion of cystine, along with lysine, arginine, and ornithine, arising from defective transport systems for these acids in the kidney and intestine; renal function is sometimes compromised by cystine crystalluria and nephrolithiasis; occurs in certain heritable diseases, such as Fanconi syndrome (cystinosis) and hepatolenticular degeneration.
[cystine + G. ouron, urine]
cystinuriaAn autosomal recessive disorder featuring abnormal amounts in the urine of the amino acids cystine, lysine, ornithine and arginine. The defect is in the kidney tubules which contain transporters for the amino acids that reabsorb them from the filtrate back into the blood. There is a second subtype of the disease in which reabsorption of cystine is normal but in which that of the other three amino acids is defective. The main disadvantage is the formation of hard cystine urinary stones. The mutated cystinuria gene codes for the amino acid transporters in the kidney tubules.
n elevation of cystine in urine.
cys·ti·nu·ri·a(sis'ti-nyūr'ē-ă) [MIM*220100, *104614, *600918]
Excessive urinary excretion of cystine, along with lysine, arginine, and ornithine.
[cystine + G. ouron, urine]
n a hereditary defect caused by the dysfunctional reabsorption of the amino acid cystine into the kidneys; it results in regular, abnormally high levels of cystine in urine.
a hereditary condition characterized by persistent excessive urinary excretion of cystine, lysine, ornithine and arginine, due to impairment of renal tubular reabsorption of these amino acids. The predominant clinical manifestation is the formation of urinary cystine calculi. See also urolithiasis.