Alport Syndrome

Alport Syndrome is an inherited disease that affects the glomeruli, the tiny blood vessels within the kidneys that filter the blood of its wastes.  It was first described by an English doctor, A. Cecil Alport.  Because of the way Alport Syndrome is inherited, the disease tends to be more severe in men than in women.

The gene for Alport Syndrome generally is located on the X chromosome, which is one of the chromosomes that determines an individual's sex.  The disease is less severe in women because they have two X chromosomes.  A normal gene on one of the X chromosomes limits the effects of the Alport gene.  Since men only have one X chromosome, there is no normal gene to oppose the effects of the Alport gene, resulting in more severe disease.

About 15-20% of the people who have Alport Syndrome do not have a family history of the disease.  In these cases, Alport Syndrome results from new mutations in the gene that is affected in Alport Syndrome.  In this case, the affected person is the first member of the family to develop the disease.

Signs and Symptoms

The central feature of the disease is the presence of blood in the urine.  Boys with Alport Syndrome develop this symptom in infancy, while girls who carry the Alport gene may or may not have it.

Another important symptom of Alport Syndrome is hearing loss.  In boys with the disease, hearing loss is usually detectable by 8-10 years of age, and it may be severe enough to require the use of hearing aids.  Hearing loss in girls tends to be much milder, rarely resulting in the need for hearing aids.

Some boys with Alport Syndrome lose large amounts of protein in the urine, resulting in retention of fluid and body swelling.  This condition is called "the nephrotic syndrome."  With the passage of years, boys with Alport Syndrome develop the typical signs and symptoms of kidney failure – high blood pressure, swelling and, in some cases, impaired growth.

Some people with Alport Syndrome have an eye problem called anterior lenticonus, in which the shape of the lens becomes distorted.  This can interfere with the sharpness of vision.

Diagnosis and Tests

Absolute diagnosis of Alport Syndrome can be difficult because its symptoms are similar to those of other kidney diseases, particularly benign familial hematuria (BFH).  BFH is another inherited disease that causes many members of a family to have blood in the urine.  However, it does not lead to kidney failure.

The diagnosis of Alport Syndrome is done by a careful family history and a kidney biopsy (examination of a small piece of tissue taken from the kidney).  Characteristic changes occur in the walls of the capillaries that make up the glomeruli which are seen only in people with Alport Syndrome.

Treatment and Prevention

There is currently no specific therapy for Alport Syndrome.  Treatment of the kidney disease consists of controlling high blood pressure and restricting dietary phosphorus.  Men with Alport Syndrome eventually require replacement of kidney function with dialysis or kidney transplantation.

Kidney specialists currently are evaluating new approaches designed to preserve kidney function in people with chronic kidney disease.  Methods such as dietary protein restriction and the use of a specific blood pressure medication called angiotensin converting enzyme inhibitors (ACE inhibitors) may eventually prove useful in delaying, if not preventing, the development of kidney failure in people with Alport Syndrome.

What is the outlook for Alport Syndrome?
Researchers recently isolated the gene responsible for Alport Syndrome.  The research disclosed three mutations of the gene.  This discovery not only will permit more precise diagnosis of Alport Syndrome, but it opens the possibility for future gene therapy for this disorder.

Prognosis; Complications

In most cases, Alport Syndrome does not recur in transplanted kidneys, so successful transplantation essentially cures the kidney component of the disease.

Alport Syndrome causes progressive kidney damage.  This means that the glomeruli undergo a gradual but persistent process of destruction, leading to kidney failure in many cases.  Boys with Alport Syndrome inevitably develop kidney failure, but kidney failure in girls is unusual.  The age at which boys with Alport Syndrome develop kidney failure varies from family to family.  It may occur as early as 15-20 years of age, but in some families, kidney failure does not develop until the men are 40-50 years of age.