An Overview Of Alport Syndrome

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Alport syndrome is an inherited disease that’s characterized by kidney disease, hearing loss, and eyesight problems. Alport syndrome causes kidney disease by damaging glomeruli—the tiny filters in your kidney tasked with filtering your blood. With Alport syndrome, the collagen type IV that’s found in your glomeruli, inner ear, and eyes is affected, making them unable to do their function properly. In turn, your kidneys become weak, and less and less waste is filtered from your blood. This sometimes leads to end-stage renal disease (ESRD).

The disease affects the ears, leading to hearing loss in early adolescence or late childhood. People with Alport syndrome also sometimes develop eye problems such as an abnormally shaped lens, which may lead to cataracts and/or myopia. Also present at times are white flecks scattered around the retina called dot and fleck retinopathy. However, in general, these eye flecks don’t lead to blindness.

Complications of Alport syndrome are more common and more severe in men than in women. Alport syndrome is said to be diagnosed in 1 in 5,000 people.

Alport syndrome diagnosis
 Illustration by JR Bee, Verywell

Symptoms

The major symptoms of Alport syndrome are also its major complications, which are kidney disease, eye abnormalities, and hearing loss/problems. These symptoms also tend to manifest early in life, prior to an official diagnosis of Alport syndrome.

Symptoms of Alport Syndrome

  • Blood in urine (hematuria). This is the first symptom a person with Alport syndrome will have.
  • Protein in urine (proteinuria)
  • High blood pressure
  • Swelling in the feet, ankles and eye area. Swelling is also called edema.
  • Smooth muscle tumors (leiomyomatosis)
  • Occasional aneurysms

Causes

Alport syndrome is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes. These genes are responsible for the formation of a part of type IV collagen. Collagen is the major protein in your body that’s responsible for giving strength and support to your connective tissues.

This type IV collagen is really crucial to the work of your glomeruli, and the mutations in these genes make it so that the collagen found in the glomeruli is abnormal. This, in turn, damages your kidneys and makes them unable to clean out your blood properly.

This collagen is found in your inner ears, and abnormalities in it can lead to sensorineural hearing loss. Type IV collagen is also important in keeping the shape of your eye lens and the normal color of your retina, and it’s the abnormalities with it that cause the eye complications associated with Alport syndrome.

Alport syndrome is inherited in three different ways:

X-Linked Pattern

This is the most common way Alport syndrome is inherited, and about 80 percent of people with this disease have this form. It is caused by mutations in the COL4A5 gene. What inheritance by ‘‘X-linked pattern" means is that the gene is located on the X chromosome. Because males only have one X chromosome, one mutation of the gene on that chromosome is enough to cause kidney disease and other severe symptoms of the condition in them.

Females, on the other hand, have two X chromosomes and, accordingly, two copies of the gene, so the mutation of the gene in just one of the chromosomes is usually unable to cause the serious complications of Alport syndrome. Because of this, females that have X-linked Alport syndrome usually only experience blood in their urine and they are sometimes referred to as just carriers. It is uncommon for them to develop the other serious complications of the disease, and even when they do it is milder than in their male counterparts.

With X-linked pattern of inheritance, fathers cannot pass the condition to their sons because biologically, men don’t pass down their X chromosomes to their male children. On the other hand, every child has a 50 percent chance of inheriting the gene if the mother has the defective gene on one of her X chromosomes. Boys who inherit the defective gene will typically develop Alport Syndrome during his lifetime.

Autosomal Dominant Pattern

This is a rare form of inheritance, and it’s found in only about 5 percent of cases of Alport syndrome. People with this form have one mutation in either the COL4A3 or COL4A4 genes, meaning only one parent has the abnormal gene and passed it on. With this form of Alport syndrome, males and females experience similar symptoms at similar levels of severity.

Autosomal Recessive Pattern

This form of inheritance is found in about 15 percent of cases of Alport syndrome. A child inherits this way when both parents are carriers and each have a copy of the abnormal COL4A3 or COL4A4 gene. With this, too, males and females are affected similarly.

Diagnosis

Your doctor may first suspect that you have Alport syndrome based on your family history. The symptoms you report will also indicate the likelihood of you having this disease. To confirm, your doctor may use these two types of diagnostic tests:

  • Kidney or skin biopsy: In this test, a very tiny piece of your kidney or skin will be removed and examined with a microscope. Careful microscopic evaluation of the specimen can show the characteristic findings of Alport's.
  • Genetic test: This test is used to confirm whether you have the gene that could lead to Alport syndrome. It’s also used to determine the particular way you inherited the gene.

An early diagnosis of Alport syndrome is very imperative. This is because the complications of Alport syndrome usually manifest in childhood/early adulthood and without beginning treatment on time, the kidney disease may become fatal in early adulthood.

Other types of testing may be important to rule out other diseases on the differential diagnosis list, assess the status of the patient, or develop an initial suspicion of Alport's—however, these are not diagnostic tests. These include:

  • Urinalysis: A urinalysis test will be used to check the contents of your urine for the presence of blood or protein.
  • eGFR test: This is kidney function testing, and it estimates the rate at which your glomeruli are filtering waste. This rate is a strong marker of whether or not you have kidney disease. Blood tests such as a blood urea nitrogen (BUN) test and your creatinine levels help determine the state of your kidneys.
  • Hearing test: This test will be used to determine if your hearing has been affected in any way.
  • Vision and eye tests: This will be used to see if your vision has been affected or you have cataracts. They will also be used to check for any of the telltale signs of Alport's syndrome, such as the white flecks in the eye and abnormally shaped lens which could indicate dots and fleck syndrome.

Treatment

There isn't one single treatment for Alport syndrome, because each of the symptoms and complications are treated individually.

Kidney Disease

Managing and slowing down the progression of kidney disease is the first and primary consideration in treating Alport syndrome. In order to do this, Your doctor may prescribe:

  • Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers to lower your blood pressure, and potentially reduce protein in your urine and slow down the progression of your kidney disease
  • A limited salt intake diet
  • Water pills, also known as diuretics.
  • A low-protein diet

Your doctor will likely recommend that you see a dietitian to help you stick to your new limitations while still maintaining a healthy diet.

A lot of times, though, the kidney disease will progress to end-stage renal disease, for which you’ll either have to go on dialysis or alternatively receive a kidney transplant. 

  • Dialysis is an artificial process of removing and filtering waste from the body using a machine. The dialysis machine basically functions as a substitute for your kidneys.
  • Kidney transplant involves surgically replacing the defective kidney with a healthy one from a donor.

You don’t necessarily have to be on dialysis before you can get a kidney transplant and, ultimately, your doctor will help you decide which option will be better for you.

High Blood Pressure

Your doctor will prescribe the appropriate pills/medication to help keep your blood pressure under control. Some of these medications are ACE inhibitors, beta blockers, and calcium channel blockers. These help to reduce your chances of developing heart disease and also slow down the progression of your kidney disease.

Eye Problems

Your doctor will refer you to an ophthalmologist to help solve vision problems, if any, caused by the abnormality in the shape of your lens. This can take the form of changing the prescription of your glasses or you undergoing cataract surgery. The white flecks in the eyes do not affect vision in any way, so usually, there’s no attention paid to treating it.

Hearing Loss

If you develop hearing loss due to your Alport syndrome, chances are it’ll be permanent. Fortunately, you can get hearing aids that are very effective in helping with this.

In general, you may also benefit from lifestyle changes like keeping active, eating well, and maintaining a healthy weight.

A Word From Verywell

If you’ve been diagnosed with Alport syndrome, you should discuss your treatment options extensively with a doctor because each individual case is different in terms of severity and which organs are affected. It is crucial to seek expert care from a specialized doctor who is experienced in the care of this unusual disease. You should also try to have your family evaluated by genetic counseling to determine who else may be at risk. Alternatively, if you don't have the disease but are a carrier or you have a family history of it, you should undergo genetic counseling before starting a family. This will enable you to know the best ways to reduce your chances of passing the genetic mutation to your future children if you plan to have any.

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