$Unique_ID{BRK03645} $Pretitle{} $Title{Cystinosis} $Subject{Cystinosis Cystine Storage Disease Fanconi II Lignac-Fanconi Syndrome INFANTILE CYSTINOSIS: Nephropathic Cystinosis Infantile Fanconi Syndrome with Cystinosis Dwarfism with Rickets de Toni-Fanconi Syndrome Abderhalden-Kaufmann-Lignac Syndrome Lignac-Debre-Fanconi Syndrome Nephrotic-Glycosuric-Dwarfism-Rickets-Hypophosphatemic Syndrome, Aminoaciduria-Osteomalacia-Hyperphosphaturia Syndrome ADOLESCENT CYSTINOSIS (Intermediate Cystinosis and Juvenile Cystinosis) Adult Cystinosis (Benign Cystinosis) Fanconi Syndrome (Renal)} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1991, 1993 National Organization for Rare Disorders, Inc. 59: Cystinosis ** IMPORTANT ** It is possible that the main title of the article (Cystinosis) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Cystine Storage Disease Fanconi II Lignac-Fanconi Syndrome DISORDER SUBDIVISIONS: INFANTILE CYSTINOSIS: Nephropathic Cystinosis Infantile Fanconi Syndrome with Cystinosis Dwarfism with Rickets de Toni-Fanconi Syndrome Abderhalden-Kaufmann-Lignac Syndrome Lignac-Debre-Fanconi Syndrome Nephrotic-Glycosuric-Dwarfism-Rickets-Hypophosphatemic Syndrome, and Aminoaciduria-Osteomalacia-Hyperphosphaturia Syndrome ADOLESCENT CYSTINOSIS (Intermediate Cystinosis and Juvenile Cystinosis) Adult Cystinosis (Benign Cystinosis) Information on the following diseases can be found in the Related Disorders section of this report: Fanconi Syndrome (Renal) 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. Cystinosis is an inherited disorder of the transport of cystine out of parts of cells called lysosomes. Lysosomes are particles bound in membranes within cells. Cystine is an amino acid found in many proteins in the body. This disorder is characterized by the accumulation of cystine in tissues throughout the body, which can cause certain organs to malfunction. Three forms of Cystinosis are recognized. Infantile Nephropathic Cystinosis is the most severe form of the disease. Symptoms can appear as early as 6 to 12 months of age and if left untreated, may lead to kidney failure by 10 years of age. In benign (or adult) Cystinosis, crystalline cystine accumulates primarily in the cornea of the eyes. In people with the intermediate form of Cystinosis (also called juvenile or adolescent Cystinosis), kidney and eye symptoms are apparent in the teens or twenties. One of the major complications of Cystinosis is the renal fanconi syndrome. (See the related disorders section of this report for information about Renal Fanconi Syndrome.) Symptoms People with Cystinosis accumulate excessive amounts of cystine in the lysosomes of all tissues. The early symptoms of this disorder typically involve the kidneys and eyes. Individuals with Cystinosis have six-sided (hexagonal) or rectangular cystine crystals present in their bone marrow samples (aspirates), white blood cells (leukocytes), and/or the membranes that line the rectum (rectal mucosa). These crystals are also found in the corneas and membranes that line the eyes (conjunctiva). People who have inherited only one gene of a pair that causes Cystinosis (heterozygotes) have slightly elevated levels of intracellular cystine, but no symptoms. People with two genes that cause Cystinosis will have symptoms. Cystine accumulation in the kidneys impairs the ability of the kidneys to save mineral salts, causing abnormally low levels of sodium, potassium and phosphate in the blood. It also causes excessive urination (polyuria) and excessive thirst (polydipsia). These conditions together comprise the Renal Fanconi Syndrome. The accumulation of cystine crystals in the cornea and conjunctiva of the eyes may cause an increased sensitivity to light (photophobia), headaches, and itching and/or burning of the eyes. A physician is able to see crystals in the cornea of the eyes through a slit- lamp examination. The symptoms of Infantile Nephropathic Cystinosis typically appear before the age of 1 year. Infants with this disorder usually have a patchy loss of color (depigmentation) in the retina of the eyes and an abnormal sensitivity to light (photophobia). Hypophosphatemic Vitamin D-Resistant rickets (abnormal bone formation) may occur, as well as poor growth; the child fails to thrive and is pale and thin. The bones may be soft, and result in deformities that appear as the child grows older. Untreated Cystinosis leads to kidney (glomerular) failure by 10 years of age. (For more information on Vitamin D-Resistant Rickets, choose "Rickets" as your search term in the Rare Disease Database.) The symptoms of kidney dysfunction associated with Intermediate or Juvenile Cystinosis resemble those of the infantile form of the disease, but are generally milder. Abnormal bone formation (Rickets) sometimes occurs. The adult form of Cystinosis is typically benign. This form of the disease is primarily characterized by crystals in the corneas of the eyes. Ocular itching and burning may also occur, but kidney function remains intact. Causes Cystinosis 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. Affected Population Cystinosis is a rare disorder that affects males and females in equal numbers. Approximately 200 cases have been identified in the United States. Related Disorders Symptoms of the following disorders can be similar to those of Cystinosis. Comparisons may be useful for a differential diagnosis: The renal fanconi syndrome is a rare disorder characterized by abnormal kidney function (proximal tubular), particularly involving excessive excretion of glucose, phosphates, amino acids, bicarbonate, water, potassium, calcium, sodium, and carnitine. Other symptoms of this disorder may include abnormally low levels of potassium in the blood (hypokalemia), excessive urination (polyuria), excessive thirst (polydipsia), and/or abnormally low levels of phosphate in the blood (hypophosphatemia). The renal fanconi syndrome may be, besides nephropathic Cystinosis, associated with other hereditary metabolic conditions including tyrosinemia, galactosemia, fructose intolerance, glycogen storage disease type I, Wilson Disease, familial Nephrosis, and Lowe Syndrome. The onset of the renal fanconi syndrome is also associated with the use of certain aminoglycosides and outdated tetracycline. It has been associated with poisoning by heavy metals or other chemicals. Therapies: Standard Benign forms of Cystinosis require little or no treatment. Nephropathic Cystinosis is treated symptomatically. Renal tubular dysfunction requires a high intake of fluids and electrolytes to prevent excessive loss of water from the body (dehydration). Sodium bicarbonate, sodium citrate, and potassium citrate may be administered to maintain the normal electrolyte balance. Phosphates and Vitamin D are required to correct the impaired resorption of phosphate into the kidneys (hypophosphatemia) and prevent rickets. Hemodialysis or kidney transplantation is required in end stage renal disease. Kidney transplantation is successful in this condition, however linear growth does not improve. Corneal transplantation has been successfully performed in Cystinosis patients using related donors. Cystinosis can be detected during pregnancy by a special obstetric procedure in which a small amount of amniotic fluid is removed for laboratory analysis (amniocentesis). In another prenatal procedure, chorionic villus sampling, a small amount of tissue from the placenta is removed and examined. Genetic counseling will be of benefit for patients and their families. Therapies: Investigational Cysteamine and phosphocysteamine, which are both cystine depleting agents, are being investigated for the treatment of Cystinosis. These two drugs lower cystine levels within cells. Cysteamine has a strong, unpleasant odor, a disadvantage that phosphocysteamine lacks. For more information patients may wish to have their physicians contact: Jess Thoene, M.D., University of University of Michigan, Ann Arbor, MI, 48109 This disease entry is based upon medical information available through June 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 Cystinosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Cystinosis Foundation, Inc. 17 Lake Ave. Piedmont, CA 94611 (800) 392-8458 (415) 601-6940 National Kidney and Urologic Diseases Information Clearinghouse Box NKUDIC Bethesda, MD 20892 (301) 468-6345 Research Trust for Metabolic Diseases in Children Golden Gate Lodge, Weston Road Crewe CW1 1XN, England Telephone: (0270) 250244 Jerry Schneider, M.D. University of California at San Diego 9500 Gilman Drive La Jolla, CA 92093 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Ave. 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. Pp. 92-94. THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., Editors; McGraw Hill, 1989. Pp. 2619-2635. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 482-483. THE KIDNEY, 4th Ed.; Barry M. Brenner, M.D. and Floyd C. Rector, Jr., M.D., Editors; W. B. Saunders Company, 1991. Pp. 1618, 1758. NIH CONFERENCE. CYSTINOSIS: PROGRESS IN A PROTOTYPIC DISEASE: W.A. Gahl, J.G. Thoene et al.; Ann Intern Med (Oct 1988; 109(7)). Pp. 557-69.