Alport syndrome is a rare genetic condition leading to kidney disease, as well hearing loss and eye problems. The disorder, also going under the name Hereditary Nephritis, Hereditary Deafness and Nephropathy, among others, is more common in boys.
According to the National Organization for Rare Disorders (NORD), about one in 5,000-10,000 people in the U.S. are born with the disease, which can be caused by three types of genetic mutations, all affecting the production of collagen IV, that is required for the kidneys to work properly.
The most common form of the disease is called X-linked Alport syndrome (XLAS), and is caused by mutations in the Col4A5 gene. The gene sits on the X chromosome, and since men have only one X chromosome, this condition is more common and tends to be more severe in males.
Two other types of Alport syndrome, called autosomal recessive (ARAS) and autosomal dominant (ADAS), are caused by mutations in the Col4A3 and Col4A4 genes. Depending on the type of mutations, the disease will be either recessive or dominant.
Alport onset and the severity of its symptoms can vary widely, and are mainly determined by the type of mutations a patient carries. Likewise, the course of the disease may be more or less aggressive.
Blood in the urine is usually the first sign that a person with Alport has kidney disease. The amount of blood is, however, not always visible, and this so-called microscopic hematuria is usually detected by urine analysis.
The amount of blood in the urine can be higher when a patient has a cold, or the flu, and is then visible as discolored urine.
As people with Alport grow older, higher levels of proteins such as albumin are also found in the urine, since the kidneys are less able to filter the urine. As the kidney disease advances further, the organ begin to lose their ability to function, most often leading to high blood pressure.
Ultimately, the kidneys will stop working altogether, and patients arrive at what doctors refer to as end-stage renal disease. This condition is characterized by symptoms that may not always be intuitively linked to the workings of the kidneys, such as weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, increased thirst and frequent urination.
Men with XLAS can reach this stage in their teens, but women and patients with the other types of Alport do not develop kidney failure until later in life, if at all.
Since the type of collagen affected by Alport syndrome is also present in the ears, progressive hearing loss is the second main feature of the disease. In boys with XLAS, it usually becomes evident in their teens, and by the age of 40, most men are affected by hearing loss.
As with the kidney disease, the onset, severity and course of the hearing loss differs among the different types of the disease.
The eyes are also affected by a lack of collagen IV in Alport, and may impact the lens, retina, or cornea. Usually, these problems do not cause blindness, and people with ADAS usually do not have eye problems. Eye symptoms vary from a decreased eyesight to pain and cataract.
A small number of men with Alport syndrome have also developed aneurysms of the aorta. Aneurysms are weakened portions of a blood vessel wall that start bulging, and risk to rupture and cause severe internal bleeding.
If doctors suspect Alport syndrome, there is a variety of tests to confirm the disease.
Urine samples are used to check for evidence of blood or proteins. XLAS can be diagnosed with the help of a skin biopsy, where a pathologist looks for the presence of a specific type of collagen. Kidney biopsies can also be used to detect all three forms of Alport syndrome.
Genetic testing is the most accurate way to diagnose the condition and its type, but is only possible at specialized centers.
Since the condition is inherited, family history also helps physicians in setting a diagnosis. If a woman knows she carries Alport mutations, prenatal genetic testing may be performed.
There is no cure for Alport syndrome, and treatment is directed at the individual symptoms of each patient. Some patients may be treated with a blood pressure medicine called angiotensin-converting enzyme (ACE) inhibitors. This is particularly used in patients with high levels of protein in the urine, and has been shown to slow the progression of the kidney disease. Another related type of blood pressure medicine, angiotensin receptor blockers, are also used.
Once the kidneys stop working, patients need to undergo frequent dialysis or a kidney transplant.
The rarity of Alport syndrome makes it difficult to gather enough patients to perform clinical trials into potential treatments.