Última actualización:
June 04, 2020
Años publicados: 1986, 1987, 1988, 1990, 1991, 1993, 1999, 2003, 2007, 2008, 2017, 2020
NORD gratefully acknowledges David J. Sas, DO, Pediatric Nephrologist, Mayo Clinic, Rochester, MN, for assistance in the preparation of this report.
Cystinuria is an inherited metabolic disorder characterized by excessive amounts of undissolved cystine in the urine, as well as three chemically similar amino acids: arginine, lysine, and ornithine. Excess cystine in the urine can lead to the formation of crystals and stones (calculi) in the kidney, bladder, and/or urinary tract (ureters). Some people with cystinuria do not form stones, while others frequently form stones.
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. The amino acids lysine, arginine, and ornithine are also excreted in massive amounts by people with this disorder, but they dissolve more readily in the urine and are not associated with any particular symptoms.
The initial symptom of cystinuria is usually sharp pain in the lower back or side of the abdomen (renal colic). Other symptoms may include blood in the urine (hematuria), obstruction of the urinary tract, and/or infections of the urinary tract. Frequent recurrences ultimately may lead to kidney damage.
People with cystinuria typically produce jagged stones that are small, though some form very large stones. Stones may be accompanied by urinary “gravel,” which consists of yellowish-brown hexagonal crystals. All patients with urinary stones should be screened for cystinuria.
Cystinuria is caused by changes (mutations) in the SLC3A1 and SLC7A9 genes. These mutations result in the abnormal transport of cystine in the kidney and this leads to the symptoms of cystinuria.
Cystinuria is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits two copies of an altered gene for the same trait, one from each parent. If an individual inherits one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. People who are carriers of these genes typically have slightly elevated levels of cystine and lysine in the urine. The full implications of being a carrier are not known and require further investigation. The risk for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
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.
People with cystinuria have cystine crystals in their urine that can be identified by looking at the urine under a microscope. Additionally, patients with cystinuria typically produce stones that are 100% cystine, which can be analyzed at special laboratories. Finally, cystinuria can be diagnosed through genetic testing, which may be available at medical centers that specialize in kidney stone diseases.
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 may also prevent the formation of stones. Drugs that may be prescribed to make the urine more alkaline include potassium citrate and acetazolamide. This treatment is accompanied by dietary salt and animal protein restriction.
The orphan drug alpha-mercaptopropionyl glycine, also known as tiopronin (Thiola) has been approved as a treatment for cystinuria. This drug has been shown to make cystine more soluble in patients with cystinuria and reduce the risk of crystal and stone formation.
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. This medication is rarely prescribed now because tiopronin is at least as effective and has fewer side effects. Another medicine that is used at times is captopril.
Kidney and/or bladder surgery sometimes becomes necessary, but stones commonly recur. Small stones may pass spontaneously on their own with high fluid intake and, if needed, pain medications. If spontaneous stone passage is unsuccessful, stones may be removed by a special procedure. The surgeon can view the stones through an illuminated optic instrument inserted in the urethra and passed up into the upper urinary tract. The stones are then removed with special instruments (endoscopic basket extraction). Laser techniques are also used to dissolve stones in the bladder and/or kidneys that are caused by cystinuria. Ultrasound waves have been used to break up stones but are not as effective for cystine stones.
Genetic counseling is recommended for patients and their families. Other treatment is symptomatic and supportive.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Pediatric Nephrology. 5th Ed.; Ellis D. Avner, William E. Harmon, Patrick Niaudet, Editors, Lippincott Williams and Wilkins, 2004: 711-714 and 1097-1104.
The Metabolic Basis of Inherited Disease, 6th Ed.: Charles R. Scriver, et al., Editors; McGraw Hill, 1989: 2488-2493.
Cecil Textbook of Medicine, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990: 603-608.
The Merck Manual, 16th Ed.: Robert Berkow Ed.; Merck Research Laboratories, 1992: 2084.
Birth Defects Encyclopedia, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990: 483-484.
The Kidney, 4th Ed.; Barry M. Brenner, M.D. and Floyd C. Rector, Jr., M.D., Editors; W.B. Saunders Company, 1991:1602-1604.
JOURNAL ARTICLES
Pathophysiology and treatment of cystinuria. Chillaron J, et al. Nature Reviews Nephrology 2010; 6:424-434.
Milliner DS. Cystinuria. Endocrinol Metab Clin North Am. 1990 Dec 19;(4);889-907.
INTERNET
Cystinuria. Genetic and Rare Diseases Information Center. Last updated: 5/12/2015. https://rarediseases.info.nih.gov/diseases/6237/cystinuria. Accessed May 19, 2020.
Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Entry Number 220100 Last Update: 04/26/2017. https://www.omim.org/entry/220100. Accessed May 19, 2020.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/