Cystinuria

Cystinuria

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Cystinuria is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Cistinuria
  • Cystine-Lysine-Arginine-Ornithinuria
  • Cystinuria with Dibasic Aminoaciduria

Disorder Subdivisions

  • Cystinuria, Type I
  • Cystinuria, Type II
  • Cystinuria, Type III
  • Hypercystinuria

General Discussion

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 an individual 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 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.



The symptoms of Cystinuria develop due to the abnormal transport of cystine

Affected Populations

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.

Standard Therapies

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 potassium citrate, and acetazolamide. This treatment is accompanied by dietary salt restriction.



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. In case of a shortage of Thiola, physicians and pharmacists may contact Mission directly to obtain Thiola for cystinuria patients. To do so, they should call 1-800 531-3333 to request the patient and physician acknowledgement forms. Instructions for returning these forms to Mission have been posted on NORD's Web site. Another medicine that is used at times is captopril.



Kidney and/or bladder surgery sometimes becomes necessary, but stones (calculi) commonly recur. Small stones may pass spontaneously with high fluid intake and if needed pain medications. If unsucessful they 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.

Investigational Therapies

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 National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



As of this writing (2008), there were three clinical trials for cystinuria listed on www.clinicalstrials.gov. One is investigating kidney stones and their cause. This study is sponsored by the Indiana Kidney Stone Institute, Indiana University School of Medicine, and University of Chicago. For information, contact Shelly Handa, RN, at (317) 962-0870 or shanda@clarian.org.



The second, sponsored by the Mayo Clinic, involves an herbal substance known as Cystone that is being studied for its effectiveness in dissolving kidney stones and preventing the formation of new ones. For information on this study, Ellen R. Olson at (507) 255-3984 or olson.ellen@mayo.edu.



The third, sponsored by Mario Negri Institute of Pharmaceutical Research, in Bergamo, Italy, studies the genetic aspects of the disease. Contact Erica Daina, MD daina@marionegri.

References

TEXTBOOKS

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.



ARTICLES

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 (Feb 1984; 131(2)). Pp. 216-19.



Pediatric Nephrology. 5th Ed.; Ellis D. Avner, William E. Harmon, Patrick Niaudet, Editors, Lippincott Williams and Wilkins, 2004. Pp. 711-714 and 1097-1104.



FROM THE INTERNET

Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 11/17/98, Entry Number 220100; Last Edit Date 12/11/98, Entry Number 600918.

Resources

Cystinuria Support Network

22814 NE 21st Place

Redmond, WA 98053

Tel: (425)868-2996

Fax: (425)897-0675

Email: sue@cystinuria.com

Internet: http://www.cystinuria.com



March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



American Kidney Fund, Inc.

11921 Rockville Pike

Suite 300

Rockville, MD 20852

USA

Tel: (800)638-8299

Email: helpline@kidneyfund.org

Internet: http://www.kidneyfund.org



National Kidney Foundation

30 East 33rd Street

New York, NY 10016

Tel: (212)889-2210

Fax: (212)689-9261

Tel: (800)622-9010

Email: info@kidney.org

Internet: http://www.kidney.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



International Cystinuria Foundation

712 Great Plains Court

PO Box 271004

Fort Collins, CO 80527-1004

Tel: (970)204-0031

Email: Matthew.Lewis@colostate.edu

Internet: http://www.cystinuria.org



Rare Kidney Stone Consortium

Mayo Clinic

200 First St., SW

Rochester, MN 55901

Tel: (507)266-8265

Fax: (507)255-0770

Tel: (800)270-4637

Email: rarekidneystones@mayo.edu

Internet: http://www.rarekidneystones.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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