$Unique_ID{BRK03646} $Pretitle{} $Title{Cystinuria} $Subject{Cystinuria Cistinuria Cystine-Lysine-Arginine-Ornithinuria Cystinuria with Dibasic Aminoaciduria Type I Cystinuria Type II Cystinuria Type III Cystinuria Hypercystinuria Dibasic Aminoaciduria Lysinuria Cystinosis} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1991, 1993 National Organization for Rare Disorders, Inc. 61: Cystinuria ** IMPORTANT ** It is possible that the main title of the article (Cystinuria) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Cistinuria Cystine-Lysine-Arginine-Ornithinuria Cystinuria with Dibasic Aminoaciduria Disorder Subdivisions: Type I Cystinuria Type II Cystinuria Type III Cystinuria Hypercystinuria Information on the following diseases can be found in the Related Disorders section of this report: Dibasic Aminoaciduria Lysinuria Cystinosis General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Cystinuria is an inherited metabolic disorder characterized by the abnormal movement (transport) in the intestines and kidneys, of certain organic chemical compounds (amino acids). These include cystine, lysine, arginine, and ornithine. Excessive amounts of undissolved cystine in the urine (cystinuria) cause the formation of stones (calculi) in the kidney, bladder, and/or ureter. Four subtypes of Cystinuria are recognized. In Type I Cystinuria, there is a defect in the active transport of cystine and the amino acids (dibasic) lysine, arginine, and ornithine in the kidneys and small intestine. People who are carriers of the gene for this type of the disorder generally have no symptoms. In Type II Cystinuria, cystine and lysine transport is severely impaired in the kidneys and only somewhat impaired in the intestines. In Type III Cystinuria, kidney transport of cystine and lysine is defective; intestinal transport is normal. People who are carriers of the gene for this variety of the disease typically have slightly elevated levels of cystine and lysine in the urine. In Hypercystinuria, there is generally a moderate elevation of cystine in the urine; intestinal absorption of cystine and the dibasic amino acids is normal. Symptoms People with Cystinuria excrete abnormally high levels of cystine in the urine. The level of cystine is so high that it remains undissolved in the urine (insoluble). The amino acids lysine, arginine, and ornithine are also excreted in massive amounts by people with this disorder. However, these amino acids dissolve more readily in the urine (more soluble) and are not associated with any particular symptoms. The initial symptom of Cystinuria is usually sharp pain in the lower back (renal colic). Other symptoms may include blood in the urine (hematuria), obstruction of the urinary track (ureters), and/or infections of the urinary tract. Frequent recurrences ultimately may lead to kidney damage. People with Cystinuria typically produce stones (cystine calculi) that are generally small, with a jagged crystalline surface. These stones may be accompanied by urinary "gravel," which consists of yellowish-brown hexagonal crystals. All patients with urinary stones should be screened for Cystinuria. Causes Cystinuria is inherited as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. The symptoms of Cystinuria develop due to the abnormal transport of cystine and the dibasic amino acids. Affected Population Cystinuria is an inherited metabolic disorder that affects males and females in equal numbers. Symptoms of this disorder typically begin between 10 and 30 years of age, although elevated cystine excretion may be found in infancy. The disorder occurs in approximately 1 in 7,000 to 1 in 10,000 people in the United States. The prevalence of Cystinuria varies in different countries. Related Disorders Symptoms of the following disorders can be similar to those of Cystinuria. Comparisons may be useful for a differential diagnosis: In Dibasic Aminoaciduria, the transport of lysine, arginine, and ornithine is impaired, resulting in increased urinary levels of these amino acids. In Lysinuria, lysine transport alone is defective, with abnormally excessive amounts of lysine in the urine. Carriers of these diseases tend to have increased levels of the relevant amino acids. Cystinosis is a rare inherited disorder of cystine transport characterized by the accumulation of cystine within the cells of the body, especially in the kidneys and eyes. Symptoms of this disorder include the presence of cystine crystals in the urine, the excretion of abnormally large volumes of urine (polyuria), abnormally low levels of circulating potassium (hypokalemia), and/or renal tubular failure. The accumulation of cystine in the eyes may result in an increased sensitivity to light (photophobia), headache, and/or itching and burning of the eyes. Symptoms usually begin during infancy. (For more information on this disorder, choose "Cystinosis" as your search term in the Rare Disease Database.) Therapies: Standard The primary objective of treatment for Cystinuria is to reduce the cystine concentration in the urine. Consumption of large amounts of fluid both day and night maintains a high volume of urine and reduces cystine concentration in the urine. Making the urine more alkaline (alkalization) helps cystine to dissolve more readily in the urine and therefore may also prevent the formation of stones. Drugs that may be prescribed to make the urine more alkaline include sodium bicarbonate, citrate, and acetazolamide. Another approach to the treatment of Cystinuria is administration of d- penicillamine, although there are some risks of side effects with this drug. D-penicillamine promotes the formation of cystine in a different chemical form (mixed disulfide), which is more soluble in the urine and is excreted. The orphan drug alpha-mercaptopropionyl glycine, also known as tiopronin (Thiola) has been approved as a treatment for Cystinuria. This drug is manufactured by Mission Pharmacal of San Antonio, Texas. Thiola has been shown to lower the level of cystine in the urine of patients with Cystinuria. Kidney and/or bladder surgery sometimes becomes necessary, but stones (calculi) commonly recur. Small stones may be removed by a special procedure; the surgeon views the stones through an illuminated optic instrument and then removes them with special instruments (endoscopic basket extraction). Laser techniques and ultrasound have also been used to dissolve stones in the bladder and/or kidneys that are caused by Cystinuria. Genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational The drug succimer (meso-2-3-dimercaptosuccinic acid) is being tested as a treatment for Cystinuria. This drug may be useful in preventing the formation of cystine stones. More study needs to be done to determine the long-term effectiveness and safety of the drug. The McNeil Consumer Products Co., Camp Hill Rd., Ft. Washington, PA, 19034, has received orphan drug designation for the drug 2,3- Dimercaptosuccinic Acid (CHEMET). It is being tested in some patients with Cystinuria. It is hoped that this drug may prevent damage to the kidney in those patients with Cystinuria who are prone to recurring stones. A solution of tromethamine-E solution or an acetylcysteine-bicarbo has also been used experimentally to dissolve cystine stones. Further studies are required to determine the long term safety and effectiveness of these medications in the treatment of Cystinuria. This disease entry is based upon medical information available through April 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Cystinuria, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The National Kidney Foundation 2 Park Ave. New York, NY 10016 (212) 889-2210 (800) 622-9010 American Kidney Fund 6110 Executive Blvd., Suite 1010 Rockville, MD 20852 (301) 881-3052 (800) 638-8299 (800) 492-8361 (in Maryland) Researcher: Charles Y.C. Pak, M.D. The University of Texas Health Science Center at Dallas 5323 Harry Hines Blvd. Dallas, TX 75235 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 800-336-GENE 301-652-5553 References MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. P. 1322. THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., Editors; McGraw Hill, 1989. Pp. 2488-2493. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 603-608. THE MERCK MANUAL, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992. Pp. 2084. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 483-484. THE KIDNEY, 4th Ed.; Barry M. Brenner, M.D. and Floyd C. Rector, Jr., M.D., Editors; W. B. Saunders Company, 1991. Pp. 1602-1604. CYSTINURIA. D.S. Milliner; Endocrinol Metab Clin North Am (Dec 1990: 19(4)). Pp. 889-907. CYSTINURIA. R.D. Feld; Crit Rev Lab Sci (1988: 26(3)). Pp. 243-61. PERCUTANEOUS CATHETER DISSOLUTION OF CYSTINE CALCULI: S.P. Dretler, et al.; Journal Urology (February 1984: issue 131, 2). Pp. 216-219.