Synonyms of Alport Syndrome
- Congenital hereditary hematuria
- Hematuria-Nephropathy Deafness
- Hemorrhagic familial nephritis
- Hemorrhagic Familial Nephritis
- Hereditary Deafness and Nephropathy
- Hereditary Nephritis
- Hereditary Nephritis With Sensory Deafness
- Nephritis and Nerve Deafness, Hereditary
- Nephropathy and Deafness, Hereditary
- Autosomal Dominant Alport Syndrome (ADAS)
- Autosomal Recessive Alport Syndrome (ARAS)
- X-Linked Alport Syndrome (XLAS)
Alport syndrome is a group of hereditary disorders characterized by progressive deterioration of parts of the kidney known as basement membranes. This deterioration may lead to chronic kidney (renal) disease. Eventually, severe renal failure (end-stage renal disease or ESRD) may develop. Some types of Alport syndrome may also affect vision and hearing. Most cases of Alport syndrome have an X-linked pattern of inheritance.
Some individuals do not exhibit symptoms (asymptomatic). When symptoms are present, they can vary widely. In most cases, they are progressive.
The more common early symptoms are an abnormal urine color due to serum proteins or red blood cells in the urine. These signs suggest a decline in kidney's filtering function. Loss of hearing and/or loss of vision may occur. Hearing and vision problems tend to affect males more often than females.
As the disease progresses, the affected individual's legs may swell. There may also be swelling around the eyes.
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. A urine-like smell on the breath, pale skin (pallor), shortness of breath, hypertension, and fluid retention may also occur.
As the disease progresses, it can lead to chronic heart failure and end-stage renal disease, requiring regular dialysis.
Abnormalities of the eye may occur in certain 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). Children with Alport syndrome are often very nearsighted (myopic).
Most (about 85 percent) cases of Alport syndrome exhibit the X-linked pattern of inheritance. Almost all of those affected are male. Of the remaining cases, most have an autosomal recessive pattern of inheritance. In a small number of cases, the inheritance pattern is autosomal dominant.
Alport syndrome is caused by mutations of genes involved in the production of proteins known as collagens. The genetic defect associated with the classical form of the syndrome (XLAS) has been tracked to a site on the X chromosome (Xq22). Another form (ARAS) is associated with mutations on the long arm of chromosome 2 (2q36-q37). A third type (ADAS) may be linked to a site on chromosome 11 (11q24).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm (p) and a long arm (q). Chromosomes are further sub-divided into many bands that are numbered. For example, chromosome 2q36-q37 refers to the region between bands 36 and 37 on the long arm of chromosome 2. Similarly, chromosome Xq22 refers to band 22 of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, 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 and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is turned off and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. A male has one X chromosome, and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.
X-linked dominant disorders are also caused by an abnormal gene on the X chromosome, but in these rare conditions, females with an abnormal gene are affected with the disease. Males with an abnormal gene are more severely affected than females, and many of these males do not survive.
The prevalence rate for Alport syndrome is approximately 1 in 50,000 newborns.
The more common X-linked form of Alport syndrome affects mainly males. About 15% of newborns affected by Alport syndrome have no family history of kidney disease. There appear to be no racial or geographic concentrations related to this syndrome.
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 pseudo-gout 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 "Pseudo-gout" 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.
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.
In suspected cases of Alport syndrome, electron microscopy of a sample of kidney tissue may be performed to evaluate the condition of the basement membrane. Progressive loss of kidney function accompanied by loss of hearing is a clue to diagnosis.
Hearing aids may be required for deafness and corrective surgery for vision problems. Renal function and certain components in the blood are regularly monitored. No treatment prevents the progression of renal failure. Dialysis and/or transplantation may be initiated when ESRD develops. 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.
If kidney transplantation is indicated, great care must be taken in selecting living related kidney donors because of the slight or in apparent disease in some female family members.
Genetic counseling will be of benefit 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 website.
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Organizations related to Alport Syndrome
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FROM THE INTERNET
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Alport syndrome-Genetics Home Reference
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