BioAlport – Biomarker for Alport Disease
Alport Syndrome is an inherited disease that primarily affects the glomeruli, the tiny tufts of capillaries in the kidneys that filter wastes from the blood. The disease was first described by an English doctor named A. Cecil Alport. This disease is caused by changes in genes (mutations) that affect type IV collagen, a protein that is important to the normal structure and function of glomeruli. The earliest symptom of the disease is blood in the urine (hematuria). Alport Syndrome always affects the kidneys. Many people with Alport Syndrome also have hearing problems and abnormalities of the eyes, because the type IV collagen proteins are important to the normal structure and function of the inner ear and the eye. Other signs and symptoms may include:
Blood in the urine (hematuria), the most common and earliest sign of Alport syndrome
Protein in the urine (proteinuria)
Swelling in the legs, ankle, feet and around the eyes
These signs and symptoms may differ, based on age, gender and the genetic type of Alport Syndrome. For example, hearing and vision problems tend to be more common in males than females. High blood pressure is usually detected later in life.
The central feature of the disease is the presence of blood in the urine (hematuria). Boys with X-linked Alport Syndrome develop hematuria in infancy, and it is always present. The great majority of girls with X-linked Alport Syndrome also have hematuria; the hematuria of Alport Syndrome is usually microscopic, meaning it can only be detected with a microscope or a urine dipstick. Sometimes children with Alport Syndrome have brown, pink or red urine (gross hematuria) for several days, brought on by a cold or the flu. This gross hematuria will go away on its own and while it may be frightening, it is not harmful.
As boys with Alport Syndrome grow, they begin to show other signs of kidney disease, including protein in the urine and high blood pressure. These symptoms are often present by the time the boys are teenagers. Girls with Alport Syndrome usually do not have protein in the urine and high blood pressure until much later in life, but occasionally these symptoms appear in teenaged girls with Alport Syndrome. Progressive hearing loss is another important feature of Alport Syndrome. About 80% of boys with Alport Syndrome will develop progressive hearing loss at some point in their lives, often by the time they are teenagers. The progressive hearing loss affects both ears. Fortunately, hearing aids are usually very effective in these people. Girls with Alport Syndrome may also develop progressive hearing loss, but less frequently than boys, and usually later in life. Kidney transplantation does not improve the progressive hearing loss of Alport Syndrome.
About 15% of men with Alport Syndrome have an abnormality in the shape of the lens called anterior lenticonus. People with anterior lenticonus may have some problems with their vision, and may develop cataracts.
Alport Syndrome causes progressive kidney damage. The glomeruli and other normal kidney structures such as tubules are gradually replaced by scar tissue, leading to kidney failure. All boys with Alport Syndrome, regardless of the genetic type, eventually develop kidney failure. These boys often need dialysis or transplantation during their teenage or young adult years, but kidney failure can occur as late as 40-50 years of age in some men with Alport Syndrome. Most girls with the X-linked type of Alport Syndrome do not develop kidney failure. However, as woman with Alport Syndrome get older the risk of kidney failure increases.
All boys and girls with the autosomal recessive type of Alport Syndrome develop kidney failure, usually by their teens or young adult years. People with autosomal dominant Alport Syndrome are usually live well into middle age before kidney failure develops.
Currently, diagnosis of Alport Syndrome relies on careful evaluation of the patient's signs and symptoms, along with their family history. Hearing and vision should also be tested. The evaluation can also include a blood test, urine tests, and a kidney biopsy to determine Alport Syndrome. A genetic test can help confirm the diagnosis and determine the genetic type of Alport Syndrome.
Currently there is no specific treatment for Alport Syndrome. The same treatments that are used in people with high blood pressure and other symptoms of kidney disease are used in people with Alport Syndrome. Kidney transplantation is usually very successful in people with Alport Syndrome, and is considered the best treatment when end-stage kidney failure is approaching.
There are three genetic types of Alport Syndrome. X-linked (related to the X chromosome) is the most common form of Alport Syndrome. About 80% of the people with this disease have the X-linked type. Boys with this type are severely affected and always develop kidney failure sometime in their lives. Girls with this type usually have milder symptoms than boys, but they can develop kidney failure. The rest of the people with Alport Syndrome have either the autosomal recessive type which affects 15 percent, or the autosomal dominant type, which affects 5 percent. If one parent has the disease and passes an abnormal gene to the child, it is called dominant inheritance. In other words, only one copy of the abnormal gene is needed to cause the disease. If both parents carry the abnormal gene, and both parents pass an abnormal gene to the child, it is called recessive inheritance. Both copies of the abnormal gene are needed to cause the autosomal recessive version of the disease.