What is Alport Syndrome?

This material is intended for informational purposes only and does not constitute medical advice. Please consult with your physician for specific medical recommendations on diagnosis and treatment. References that were used to compile the following discussion include:

Overview of Alport Syndrome

Alport Syndrome is named after a British doctor, A. Cecil Alport, who in 1927 described three generations of a family with combinations of progressive hereditary nephritis and deafness. Dr. 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 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.

There are three genetic types of Alport Syndrome. X-linked Alport Syndrome (XLAS) is the most common; in these families affected males typically have more severe disease than affected females. In autosomal recessive Alport Syndrome (ARAS) the severity of disease in affected males and females is similar. There is also an autosomal dominant form (ADAS) which affects males and females with equal severity. Please see the Genetics of Alport Syndrome for more information.

Alport Syndrome is a rare disease and affects less than 200,000 people in the US. Alport Syndrome is estimated to affect approximately 1 in 5,000-10,000 people in the general population in the United States, which means that approximately 30,000-60,000 people in the United States have the disorder. Alport Syndrome is estimated to account for 3% of children with chronic kidney disease and 0.2% of adults with end-stage renal disease in the United States.

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Images of glomerular basement membrane (G), magnified x100,000, showing a normal kidney on the left and an Alport kidney on the right, illustrating Collagen IV mutations.

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 the disease progresses additional signs of kidney disease begin to show, such as protein in the urine (proteinuria) and high blood pressure.

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.

About 50% of males with X-linked disease require dialysis or kidney transplantation by age 25 years, and about 90% develop end-stage renal disease (ESRD) before 40 years of age. In female patients with X-linked Alport Syndrome, progression to ESRD was previously thought to be rare. However, recent observations have shown that as many as 12% of female patients also develop ESRD by the age of 40 years; this rate increases to 30% by the age of 60 years and 40% by age 80 years. Among female patients, risk factors for progression to ESRD include proteinuria and hearing loss. Males and females 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.

Photo illustrating cochlear basement membrane in the ear of a normal mouse on the left and an Alport mouse on the right. (Photo courtesy of Dominic Cosgrove, PhD)

Photo illustrating cochlear basement membrane in the ear of a normal mouse on the left and an Alport mouse on the right.
(Photo courtesy of Dominic Cosgrove, PhD)

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 do not experience hearing loss. It is estimated that about 80% of males with X-linked Alport Syndrome develop hearing loss at some point in their lives, often by the time they are teenagers. In females with X-linked Alport Syndrome hearing loss is less frequent and occurs later in life. Males and females with autosomal recessive Alport Syndrome typically have childhood hearing loss. Patients with autosomal dominant Alport Syndrome develop hearing loss at a later age.

Fortunately, hearing aids are usually very effective for patients with hearing loss caused by Alport Syndrome. However, hearing loss is not improved by kidney transplantation.

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.

Many 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. This can be helpful diagnostically, though, especially in women who have no other features of Alport Syndrome except hematuria (for which there are other causes).

Recurrent corneal erosion is another eye problem that can occur in people with Alport Syndrome. Individuals who suffer from this have repeated episodes of eye itchiness, and may need to take measures to protect their corneas from minor trauma such as wearing goggles when riding a bicycle.

A macular hole  is another eye issue that  affects only about 5% of patients. This results in a loss of vision and is an extension of the retinal thinning that occurs commonly in Alport Syndrome. Affected individuals will have difficulty with central vision — it will be hazy or distorted.

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