What is Alport Syndrome?

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EXPLANATION OF ALPORT SYNDROME

Alport Syndrome is named after a British doctor, Cecil A. Alport, who in 1927 described 3 generations of a family with combinations of progressive hereditary nephritis and deafness. Alport also observed that blood in the urine (hematuria) was the most common symptom and that males were affected more severely than females. Subsequently, many more families were described and the disease was named Alport Syndrome in 1961.

Alport Syndrome is an inherited disease of the kidney that can also affect the inner ear (cochlea) and eye. It is estimated to effect at least 1 in 5,000 people. It is caused by genetic mutations that affect the type IV collagen family of proteins. Type IV collagen is a major part of important tissue structures called basement membranes that are present in all tissues including the kidney, inner ear, and eye. Generally, Alport Syndrome affects boys more than girls because 80% of the time the disease is passed on by a mutation on the X chromosome (called X-linked Alport Syndrome). Boys only have one X-chromosome whereas girls have two X chromosomes. In girls, the normal X chromosome buffers the effect of the mutated gene. The other 20% of Alport Syndrome patients have the autosomal recessive or autosomal dominant form of the disease where boys and girls are equally affected. The Genetics of Alport Syndrome are discussed in more detail below.

Kidneys
Alport Syndrome always affects the kidneys. The primary symptom is blood in the urine (hematuria), which 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, associated with a cold or flu. This gross hematuria eventually stops when the child recovers and can be very frightening but is not harmful. As boys with Alport Syndrome get older, they begin to show additional signs of kidney disease, such as protein in the urine (proteinuria) and high blood pressure. These symptoms usually occur by the time the boys are teenagers.

Alport Syndrome causes damage to the kidneys by the progressive formation of scar tissue in the normal kidney structures (glomeruli and tubules). As the kidneys filter proteins out of the blood, these molecules damage the filtering system or glomeruli because of the abnormal collagen makeup. This process is known as fibrosis and it eventually leads to kidney failure. Boys with X-linked (mutation of the X chromosome) Alport Syndrome develop kidney failure by the teenage years or early adulthood, but the onset of kidney failure can be delayed until 40 to 50 years of age in some patients. Most girls with X-linked Alport Syndrome do not develop kidney failure. However, as women with Alport Syndrome age, the risk of kidney failure increases.

Boys and girls with the autosomal recessive form of Alport Syndrome will develop kidney failure by their teens or young adult years. People with autosomal dominant Alport Syndrome are usually well into middle age before kidney failure develops.

Inner Ear
Hearing loss is another symptom of Alport Syndrome. Hearing loss is never present at birth but becomes apparent by late childhood or early adolescence, generally before the onset of kidney failure. Some families with Alport Syndrome hearing is not affected. Fortunately, hearing aids are usually very effective for patients with hearing loss caused by Alport Syndrome.

It is estimated that about 80% of boys with X-linked Alport Syndrome develop hearing loss at some point in their lives, often by the time they are teenagers. In girls with X-linked Alport Syndrome hearing loss is less frequent and occurs later in life. Boys and girls with autosomal recessive Alport Syndrome typically have childhood hearing loss. Patients with autosomal dominant Alport Syndrome develop hearing loss at a later age.

Eyes
Anterior lenticonus is an abnormality in the shape of the lens of the eye and affects about 15% to 20% of patients with X-linked and autosomal recessive Alport Syndrome. People with anterior lenticonus may have a slow progressive deterioration of vision requiring patients to change the prescription of their glasses frequently. This condition may also lead to cataract formation. Some people with Alport Syndrome have abnormal pigment of the retina called dot-and-fleck retinopathy, but this does not result in any abnormalities of vision. Recurrent corneal erosion is another eye problem that can occur in people with Alport Syndrome. Individuals who suffer from this may need to take measures to protect their corneas from minor trauma such as wearing goggles when riding a bicycle.