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$Unique_ID{BRK03445} $Pretitle{} $Title{Alport Syndrome} $Subject{Alport Syndrome Hereditary Nephritis Nephritis and Nerve Deafness, Hereditary Nephropathy and Deafness, Hereditary Epstein Syndrome Type I Alport Syndrome Type II Alport Syndrome Type III Alport Syndrome Type IV Alport Syndrome Type V Alport Syndrome (Epstein syndrome) Type VI Alport Syndrome Chronic Renal Failure Benign Essential Hematuria Fabry Disease Medullary Cystic Disease Glomerulonephritis} $Volume{} $Log{} Copyright (C) 1988, 1989 National Organization for Rare Disorders, Inc. 592: Alport Syndrome ** IMPORTANT ** It is possible that the main title of the article (Alport Syndrome) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Hereditary Nephritis Nephritis and Nerve Deafness, Hereditary Nephropathy and Deafness, Hereditary Epstein Syndrome Disorder Subdivisions: Type I Alport Syndrome Type II Alport Syndrome Type III Alport Syndrome Type IV Alport Syndrome Type V Alport Syndrome (Epstein syndrome) Type VI Alport Syndrome Information on the following diseases can be found in the Related Disorders section of this report: Chronic Renal Failure Benign Essential Hematuria Fabry Disease Medullary Cystic Disease Glomerulonephritis 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. Alport Syndrome is a group of hereditary kidney disorders. They are characterized by progressive deterioration of the glomerular basement membranes (GBM's) which are microscopic parts of the kidney. This deterioration may lead to chronic renal (kidney) failure causing excess waste products in the blood (uremia). Eventually severe renal failure (end-stage renal disease or ESRD) may develop. Uremia and kidney failure may cause heart and bone problems. Some types of Alport Syndrome also affect vision and hearing. Symptoms The kidney (renal) malfunction that is characteristic of Alport Syndrome causes the loss of red blood cells and blood plasma proteins in the urine (hematuria, proteinuria). Bleeding into the glomerulus causes material (including various elements of the blood) to be excreted into the urine. Other symptoms may occur in Alport patients when chronic renal failure, uremia, or end-stage renal disease occurs. Symptoms of chronic renal failure begin gradually when the functioning nephrons (basic unit of the kidney consisting of the glomerulus and associated structures) can no longer compensate for the non-functioning nephrons. Renal bone disease may occur as a result of renal failure. This can cause abnormalities of bone, calcium, phosphorus, and vitamin D metabolism, as well as parathyroid hormone secretion which regulates calcium and phosphate levels in the blood. Uremia occurs when the kidneys fail to remove waste products from the blood. Upset stomach, which may vary from loss of appetite to severe pain, can occur along with nausea, vomiting of food and blood, weakness, fatigue, excessive need for sleep, and dry often itchy skin. Peculiar-smelling breath similar to urine, pale skin (pallor), shortness of breath, hypertension, fluid retention, and swelling (edema) may also occur. End-stage renal disease (ESRD) is the final stage in chronic renal failure when there is virtually no more functioning nephrons present. Patients with ESRD must depend upon hemodialysis machines to cleanse their blood of waste products. Abnormalities of the eye may occur in the juvenile forms of Alport Syndrome. The surface of the eye's lens may be cone-shaped (lenticonus) or spherical (spherophakia). The lens of the eye may be opaque or cloudy (cataracts). White dots may appear on the retina (retinal macular flecks or fundus albipunctatis). Children with Alport syndrome may be nearsighted (myopic). A disorder of blood platelets which help with clotting (Thrombocytopathia) may also occur in Type V Alport Syndrome. Some forms of Alport syndrome also include nerve or cochlear deafness (see Disorder Subdivision section). Alport Syndrome is classified according to three criteria: mode of inheritance, age, and features other than kidney abnormalities. 'Juvenile' forms are characterized by the occurrence of end-stage renal disease (ESRD) before the age of 31. In 'adult' forms, ESRD occurs after the age of 31. Type I Alport Syndrome is the dominantly inherited 'juvenile' form which includes kidney disease with nerve deafness and eye abnormalities. Type II Alport Syndrome is the X-linked dominant 'juvenile' form which includes kidney disease with nerve deafness and eye abnormalities. Type III Alport Syndrome is the X-linked dominant 'adult' form which includes kidney disease with nerve deafness. Type IV Alport Syndrome is the X-linked dominant 'adult' form with NO vision or hearing impairment. It is purely a kidney disease. Type V Alport syndrome is the autosomal dominant form with nerve deafness and thrombocytopathia (disorders of blood platelets). This type of Alport Syndrome is so rare that it has not yet been classified as a 'juvenile' or as an 'adult' form. In the few cases reported it appears that the incidence of ESRD in females may equal that of males. Type V is also called Epstein Syndrome. Type VI Alport Syndrome is the autosomal dominant 'juvenile' form which includes kidney disease with nerve deafness and eye abnormalities. Causes Alport Syndrome, depending on the type, may be inherited as an autosomal dominant trait or an X-linked dominant trait. It may also occur as a mutation without any family history of kidney disease. Hereditary traits including the classic genetic diseases are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child. In X-linked dominant disorders the female with only one X chromosome affected will develop the disease. However, the affected male always has a more severe condition. Sometimes affected males die before birth so that only female patients survive. In the normal kidney, the basement membranes along with other tissues tightly hold the glomeruli (which are groups of capillaries that filter water and chemicals from the blood to become urine) together. Alport patients are born with basement membranes that are thin and weak. The basement membranes progressively deteriorate interfering with the normal filtering activity of the glomeruli. This may lead to chronic renal failure when the normal- functioning nephrons can no longer compensate for the non-functioning ones. Kidney symptoms are rarely perceived until 90 to 95 % of kidney function is lost. When the kidneys no longer remove waste products from the blood, uremia occurs and the patient must be maintained on hemodialysis. Affected Population Approximately 1 in 50,000 Americans carry the Alport Syndrome gene but not all of them get Alport Syndrome. Twice as many females carry the gene, but a higher percentage of males with the gene have symptoms of the syndrome. Nearly all males with the Alport Syndrome gene will show symptoms, and will eventually develop chronic renal failure and end-stage renal disease (ESRD) usually before age 50. Most gene-carrying females manifest the same symptoms, but progression and severity of the disease are generally less severe in females who have inherited the X-linked dominant form of the disorder. Roughly 20% of females with Alport Syndrome will experience ESRD, generally at advanced ages. A fraction of the females will have no symptoms at all. About 15 to 18% of newborns affected with Alport Syndrome have no family histories of kidney disease. In these cases a mutation of a gene may cause the syndrome. There appears to be no racial or geographic concentrations of Alport Syndrome. Related Disorders Symptoms of the following disorders can be similar to those of Alport Syndrome. Comparisons may be useful for a differential diagnosis: Chronic Renal Failure can be a complication of many kidney diseases or a symptom of a variety of diseases and conditions. It occurs gradually when the kidneys can no longer filter waste products from the blood. Urinating at night (nocturia), increased urination (polyuria), red blood cells and blood plasma proteins in the urine (hematuria, proteinuria), high blood pressure, and anemia may occur. Malaise, fatigue, loss of appetite (anorexia), shortness of breath, and bad breath (halitosis) may also occur. The skin may itch (pruritus) and bruise easily. There may be bleeding in the stomach or in the intestines. Symptoms of pseudogout or gout may occur: painful, inflamed joints, waste products around the joints and in the blood. Abnormal and possibly degenerative peripheral nerves may be present (peripheral neuropathy). (For more information about these disorders, choose "Pseudogout" or "Neuropathy" as your search term in the Rare Disease database.) Familial Benign Essential Hematuria is a hereditary non-progressive kidney disease that begins in childhood. Major symptoms may include red blood cells in the urine (hematuria), kidney function impairment, and hearing deficit. Blood plasma proteins in the urine (proteinuria) and certain abnormalities of the glomerular basement membranes characteristic of Alport Syndrome are not found. Fabry Disease (also called Anderson-Fabry Disease) is a metabolic disease causing accumulation of a certain enzyme in many tissues. Burning pain in the limbs and abnormal sensations in the peripheral parts of the body (hands, feet, ears, etc.) is common. Dark-blue, red, or black areas of skin (macules) turning into hard raised spots (papules) may appear in clusters on the skin of the lower trunk, thighs, and scrotum. Eye abnormalities, cerebrovascular disease (involving blood vessels in the brain), cardiovascular disease (involving blood vessels in the heart), and high blood pressure (hypertension) may occur. Kidney failure and ESRD may also occur. (For more information on this disorder, choose "Fabry" as your search term in the Rare Disease Database). Medullary Cystic Disease is a possibly genetic kidney disease usually affecting children or young adults. Excessive urination (polyuria) is commonly the earliest symptom. Acidity of the body tissue (acidosis) with or without high chloride in the blood (hyperchloremia) may be present. Retarded growth and bone disease may occur in affected children. Chronic renal failure and uremia may also occur. Protein in the urine (proteinuria) is minimal or absent. (For more information on this disorder, choose "Medullary Cystic Disease" as your search term in the Rare Disease Database.) Glomerulonephritis is a group of kidney diseases characterized by inflammatory changes in the glomeruli of the kidney. Hematuria, proteinuria, swelling of the face, scanty urination (oliguria), hypertension, nephrotic syndrome, and chronic renal failure may also occur. Therapies: Standard Chronic renal failure caused by Alport Syndrome must be treated vigorously. Renal function and certain components in the blood are regularly monitored. Fluid intake and diet, particularly salt and protein, may be restricted and regular medications prescribed. Control of blood pressure, prompt and aggressive treatment of urinary tract and ear infections is important. Hemodialysis may be used to treat chronic renal failure and ESRD. Dialysis involves removing blood from the patient's artery, cleansing it of unwanted substances that would normally be excreted in the urine, and returning the cleansed blood to a vein. Kidney transplantation is an alternative treatment. Because of the slight or inapparent disease in some female family members, great care must be taken in selecting living related kidney donors. In patients with hearing loss, it may stabilize after successful kidney transplantation. Transplantation of the eye's cornea or removal of the eye's lens may be helpful in patients with visual problems. Genetic counseling will be of benefit for patients and their families. Other treatment is symptomatic and supportive. Therapies: Investigational Calcium Acetate is a new orphan drug being used in the treatment of hyperphosphatemia in end stage renal disease (ESRD). It is manufactured by Pharmedic Co., 130 Exmoor Ct., Deerfield, IL 60015. This disease entry is based upon medical information available through October 1989. 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 Alport Syndrome, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Hereditary Nephritis Foundation P.O. Box 731 Blanding, UT 84511 (801) 678-3382 Alport Syndrome Study c/o Drs. C.L. Atkin and M.C. Gregory Department of Internal Medicine University of Utah Salt Lake City, UT 84132 (801) 581-6709 National Kidney and Urologic Disease Information Clearinghouse Box NKUDIC Bethesda, MD 20892 (301) 468-6345 National Kidney Foundation 2 Park Avenue New York, NY 10016 (212) 689-2210 (800) 622-9010 American Kidney Fund 6110 Executive Blvd., Suite 1010 Rockville, MD 20852 (301) 881-3052 (800) 638-8299 (800) 492-8361 (MD) 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 HEREDITARY NEPHROPATHIES: M.C. Gregory, et al.; In: Textbook of Internal Medicine. Lippincott, in press, 1988. Chapter 118. ALPORT SYNDROME: C.L. Atkins, et al.; In: Diseases of the Kidney, 4th ed.; Little, Brown & Co, 1988. Pp. 617-641. MENDELIAN INHERITANCE IN MAN, 7th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 37-38, 803, 1254-1255. INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. Pp. 762-783, 860, 876-879, 1006.