Are you aware of Alport Syndrome? Let's talk about it!

Have you ever noticed that there is a little blood in your urine? Or do you sometimes feel like your hearing is a little low, or your vision is a little different? These are things that we sometimes don't pay much attention to in our daily lives. However, sometimes behind these minor symptoms there may be a condition that needs some attention, such as Alport Syndrome . So today we will talk about this in a simple way that you can understand.

What is Alport Syndrome?

Simply put, Alport syndrome is a genetic condition in which your kidneys are unable to produce Type IV collagen proteins normally.

Think about it, this ``Type IV collagen'' is made up of three collagen chains (alpha chains) twisted together like a rope. These chains are called alpha 3, alpha 4, and alpha 5. Now, if your body doesn't produce any of these chains, the other two can't join together. That's when the most severe symptoms of Alport syndrome occur.

Sometimes, all of these chains are formed in your body, but if one of them doesn't form properly, sometimes the chains can't come together, or even if they do come together, they don't work properly. In these cases, symptoms may be reduced a little.

This protein, called ``Type IV collagen'', is very important for the filtering membranes in your kidneys, ``glomerular basement membranes or GBM''. This ``(GBM)'' is what filters your blood, separating toxins and other things that the body doesn't need and helping to make urine. It also helps to keep things like blood cells and proteins in the blood in the blood instead of going into the urine.

Now, when this `(GBM)` is not working properly, blood or protein can leak into your urine. Over time, your kidneys' ability to filter urine also decreases. This increases the risk of kidney failure.

But this doesn't just affect the kidneys. This ``Type IV collagen'' is also found in your ears and eyes. So, in addition to kidney problems, someone with Alport syndrome can also have vision and hearing problems.

How do we inherit this?

There are three main genetic types of Alport syndrome. Let's take a look at what they are.

X-linked Alport syndrome (XLAS)

This is related to your X chromosome. The X chromosome is one of your two sex chromosomes (X and Y). It contains the gene that makes the alpha 5 chain `(COL4A5)`.

Now, look, a male has one X chromosome and one Y chromosome. A female has two X chromosomes. Because males have only one defective X chromosome, they are more likely to have severe symptoms. Because females have one defective X chromosome and one healthy X chromosome, their symptoms are usually milder.

A man passes his Y chromosome to his sons. Therefore, they cannot pass on `(XLAS)` to their sons. However, a man passes his X chromosome to all of his daughters. Therefore, all of his daughters can develop Alport syndrome.

A woman passes on one of her two X chromosomes to her child, regardless of whether the child is a boy or a girl. Therefore, she has a 50% chance of passing on `(XLAS)` to any child.

This is the most common type of Alport syndrome, accounting for between 60% and 80% of all Alport syndrome patients.

Autosomal recessive Alport syndrome (ARAS)

"Autosomal" refers to the 23 pairs of autosomal genes. "Autosomal recessive" refers to the pattern of inheritance. If one parent has an autosomal recessive trait, they will not show symptoms. For it to be passed on to their children, both parents must carry the trait. However, because they do not have symptoms, they do not even know they have it.

In Alport syndrome, the genes encoding the alpha 3 (COL4A3) and alpha 4 (COL4A4) proteins are located on chromosome 2. "Recessive" means that mutations in both genes of a gene pair are required for the disease to occur.

So, in `(ARAS)`, there is a mutation in either the genes encoding the alpha 3 or alpha 4 proteins on chromosome 2. `(ARAS)` is not gender-dependent, so the inheritance and severity of symptoms are the same for everyone.

If you have `(ARAS)`, your children have a 50% chance of passing on one of these faulty genes. This usually does not cause Alport syndrome. However, there is a 25% chance of passing on both faulty genes to your children. If this happens, your child will have `(ARAS)`.

(ARAS) accounts for about 15% of Alport syndrome patients.

Autosomal dominant Alport syndrome (ADAS)

"Dominant" means that a disease can be caused by a mutation in only one gene in a pair of genes. In ADAS, there is a mutation in one of the genes that encode the protein COL4A3 or COL4A4 on chromosome 2.

ADAS is not gender-dependent, so the heritability and severity of symptoms are similar for everyone.

If you have ADAS, there is a 50% chance that your children will pass on this defective gene and develop ADAS.

(ADAS) accounts for between 25% and 35% of Alport syndrome patients.

Who does this affect? ​​How common is it?

Alport syndrome can affect anyone. It is an inherited condition, meaning that one or both parents pass it on to their child. However, in about 15% of cases, it can develop even if both parents do not have the mutated gene.

Doctors think Alport syndrome is a rare condition . Researchers say that fewer than 200,000 people in the United States have it. Worldwide, the prevalence is about one in 50,000 live births. However, as researchers continue to study the condition, they are finding people with fewer symptoms. So Alport syndrome may be more common than currently known.

How does Alport syndrome cause kidney failure?

If you have Alport syndrome, the glomerular basement membranes that I mentioned earlier don't filter properly. So blood and proteins leak into the urine. Not only that, but the cells on either side of those membranes don't get the proper support. Then those cells become irritated and inflamed . These cells called podocytes make the GBM. When the surrounding cells become inflamed, these podocytes try to put more type IV collagen into the GBM. When that happens, the GBM thickens and becomes disorganized. This is what causes protein to leak into the urine (proteinuria).

Over time, as more protein passes into the urine, the GBM thickens, and scar tissue (fibrosis) can form. As a result, your kidneys begin to lose their ability to clean your blood. This is called chronic kidney disease (CKD). As more scar tissue builds up, kidney function gets worse, and eventually the kidneys stop working (kidney failure).

What are the main symptoms of Alport syndrome?

Symptoms may vary depending on the type you have. The main symptoms are:

• Blood in the urine that you can't see (microscopic hematuria).
• The presence of protein in the urine (proteinuria).
• Chronic kidney disease (CKD) or kidney failure.
• Hearing loss.
• Eye problems.

The first sign of Alport syndrome is microscopic hematuria. This means that your defective GBM is causing red blood cells to leak into your urine. This is not visible to the naked eye, but can only be seen under a microscope. Males with XLAS and anyone with ARAS can have microscopic hematuria from birth. Many females with XLAS develop microscopic hematuria over time. Not everyone with ADAS develops microscopic hematuria.

Chronic kidney disease (CKD) develops when kidney function begins to decline. Many people do not show symptoms of CKD until their kidneys are inoperable.

Symptoms of kidney failure:

• Swelling (edema), especially around the hands or ankles.
• Extreme fatigue.
• Nausea and vomiting.
• Muscle cramps.

Hearing loss is more common in men with XLAS and ARAS. But it can happen to anyone with Alport syndrome. Hearing loss happens gradually. Many people don't notice it until it's too late. Many people have difficulty hearing high-pitched sounds, and some may eventually lose all hearing. You may eventually need to use hearing aids. In severe cases, you may even lose your hearing completely (deafness).

There are also various problems with the eyes. Some people are more likely to have corneal abrasions, which take longer to heal. This can cause watery eyes and pain, but usually does not cause vision loss. Some people have problems with the clear part of the eye, the lens, which helps focus vision, and can eventually develop cataracts.

If you have Alport syndrome and are experiencing hearing or vision problems, see a doctor immediately.

What causes Alport syndrome?

Simply put, this is caused by mutations in your collagen genes.

Is this contagious?

No, Alport syndrome is not a contagious disease. It is not transmitted from one person to another through close contact. It is an inherited condition.

How do you recognize this?

If you have microscopic hematuria or chronic kidney disease, a doctor may suspect Alport syndrome. If someone in your family has Alport syndrome, tests can detect it. If no one in your family has it, a doctor can diagnose you based on your medical history and additional tests.

The doctor will examine your symptoms and ask about your family medical history. Various tests can also help diagnose this. These tests include:

• Urinalysis: This tests the appearance, chemistry, and microscopic properties of your urine. It can detect whether there is blood or protein in the urine.
• Creatinine clearance test or cystatin C blood test: These tests measure the levels of creatinine and cystatin C, a waste product in your blood. This can show how well your kidneys are filtering your blood.
• Estimated glomerular filtration rate (eGFR): This is a value that a doctor calculates from either creatinine or cystatin C. It estimates how well your kidneys are cleaning your blood.
• Kidney biopsy: A doctor takes a few very small pieces of your kidney tissue and examines them under a microscope in a lab. These samples show the different patterns that are affecting your kidneys. In Alport syndrome, the defective GBMs appear thin, but there may also be areas of thickening. If the disease is severe, it can show scarring of the filtering units and supporting structures.
• Genetic testing: This can identify mutations in your collagen genes. This will require a visit to a specialized genetics clinic. A doctor will do this with a blood test or a saliva sample.
• Hearing test (audiogram): If a doctor suspects Alport syndrome, they may order a hearing test. Anyone with Alport syndrome should have this test. This test should be done every few years to see if hearing loss is decreasing or getting worse.
• Eye exam: This test should be performed by an eye specialist who specializes in diagnosing and treating eye diseases. They will examine your vision and look at the surface of your eye (cornea), lens, and back of your eye (retina) to see if Alport syndrome has affected your vision. They may also do an imaging test called optical coherence tomography (OCT).

Can Alport syndrome be cured? What are the treatments?

There is no cure for Alport syndrome. Researchers are working on gene therapies that correct the defective genes, but they are not yet successful. Even if a successful gene therapy is developed, it will be years before we have it. However, there are treatments that can slow the decline in kidney function and delay kidney failure.

A doctor may prescribe things like:

• Angiotensin-converting enzyme (ACE) inhibitors: These lower your blood pressure, reduce protein in your urine, and help protect your kidneys. Men with (XLAS) and anyone with (ARAS) should start taking ACE inhibitors after diagnosis. Women with (XLAS) or (ADAS) should start taking ACE inhibitors as soon as they start seeing protein in their urine, or at the time of diagnosis.
• Angiotensin II receptor blockers (ARBs): ARBs are similar to ACE inhibitors and have the same benefits.
• Sodium-glucose transported type 2 (SGLT-2) inhibitors: If you have CKD or Alport syndrome, SGLT-2 inhibitors can help reduce your risk of kidney failure. Your doctor may add these to your ACE inhibitor or ARB. Not all SGLT-2 inhibitors are approved to treat CKD. Your doctor may not give you these if your eGFR is very low.
• Sodium-controlled diet: Limiting the amount of salt and sodium in your diet can help lower blood pressure and maintain kidney and heart health.

Can a kidney transplant cure Alport syndrome?

Yes and no. With a kidney transplant, you get a kidney with normal ``Type IV collagen'' and filtration membranes. Therefore, Alport syndrome will not return in the new kidney.

However, a kidney transplant will not help with other symptoms, such as hearing loss and eye problems.

How can we prevent this?

Alport syndrome cannot be prevented. However, being aware of your family history can help you identify it early. It can also help you prevent your children from passing it on.

Early diagnosis of Alport syndrome and initiation of treatment with ACE inhibitors/ARBs and SGLT-2 inhibitors is the best way to delay kidney failure.

If a doctor says you have blood in your urine, it's a good idea to get additional tests for Alport syndrome, especially if you have hearing problems or decreased kidney function.

If someone in your family has a history of blood in the urine (hematuria), a doctor should check your urine for blood and do blood tests to check your kidney function.

What will my life expectancy be like if I have Alport syndrome?

Men with `(XLAS)` and anyone with `(ARAS)` often develop kidney failure and hearing loss before the age of 30.

Women with XLAS usually have a normal lifespan. You may have microscopic hematuria, proteinuria, CKD, or kidney failure and hearing loss. Everyone responds differently. But 16% of women will have kidney failure by age 60, and 20% will by age 80.

People with `(ADAS)` can have different responses, and they can have a normal lifespan. Hearing loss and kidney failure are less common in `(ADAS)`.

Chronic kidney disease (CKD) and kidney failure usually shorten the life span of people with Alport syndrome. CKD increases the risk of death from heart disease and strokes. Kidney failure is fatal without dialysis or a kidney transplant. Even with treatment, kidney failure increases the risk of death from heart disease, stroke, and infections. Depending on how well a transplanted kidney works, a kidney transplant may help you live a normal life.

How do I take care of myself?

If you have Alport syndrome, a doctor will help you develop the best treatment plan. This may include medications and lifestyle changes.

Medical treatment

• Take ACE inhibitors, ARBs, or SGLT-2 inhibitors as prescribed by your doctor.
• Avoid taking painkillers (non-steroidal anti-inflammatory drugs - NSAIDs). These can accelerate kidney failure if you have abnormal kidney function or Alport syndrome.
• Get your hearing checked. If your hearing is severely impaired and your doctor recommends hearing aids, it's a good idea to use them. Otherwise, you may find it difficult to communicate with others, making you feel lonely and isolated. These feelings of isolation can lead to depression. Hearing aids can improve your relationships with those around you, improve your mood, and help you manage or prevent depression.
• Take care of your mental health. Having a genetic condition can be lonely, and learning that Alport syndrome can cause kidney failure or hearing loss can increase your risk of depression. It's important to talk to your doctor about any mental health issues you're having and get the treatment you need. Ask your doctor if there are support groups for people with Alport syndrome. Meeting people like that can help you feel less alone.

Lifestyle changes

• Reduce the amount of salt in your food.
• If you have CKD, you may need to follow a special diet. This may include reducing your intake of animal protein, switching to a plant-based diet, avoiding foods high in potassium if you have high blood potassium levels, and limiting your protein intake if you have high blood phosphorus or parathyroid hormone (PTH) levels.
• Following a heart-healthy lifestyle can help reduce your risk of heart disease, diabetes, and other conditions that can lead to kidney failure. Exercises like brisk walking, jogging, swimming, cycling, and jumping rope are good. It's also good to maintain a healthy weight that's right for you.
• Avoid smoking and other tobacco products. See a doctor if you need help quitting smoking.

When should I see a doctor?

See a doctor if you have blood in your urine, hearing loss, or vision loss. These could be signs of Alport syndrome.

If you have Alport syndrome, make sure your doctor refers you to a kidney specialist (nephrologist).

If someone in your family has Alport syndrome, see a doctor to see if you have it too.

What questions should I ask my doctor?

If you think you may have Alport syndrome, or if someone in your family has Alport syndrome, ask your doctor these questions:

• Do you know how to recognize Alport syndrome?
• Can you refer me to a specialist who knows how to diagnose Alport syndrome?
• Is there blood in my urine?
• Is my kidney function declining?
• Should I get a hearing test or an eye test?
• Should I have a kidney biopsy?
• Should I get a genetic test?

If you have Alport syndrome, ask your doctor these questions:

• How do you know I have Alport syndrome?
• When can I be referred to a kidney specialist (nephrologist) who knows about Alport syndrome?
• What type of Alport syndrome do I have?
• Will I pass Alport syndrome on to my children?
• What is my `(GFR)`?
• How much protein is in my urine?
• When do you start an `(ACE inhibitor)` or `(ARB)`?
• Will I benefit from an SGLT-2 inhibitor?
• What other medications do you recommend?
• How often should I schedule appointments to check my kidney health?
• How often should I have my hearing tested?
• Should I see an ophthalmologist to check my eyes?
• Can you recommend support groups for people with Alport syndrome?

Alport syndrome is a condition that damages the blood vessels in your kidneys. Mutations in your genes affect how your kidneys work, and can also affect your hearing and vision.

You may experience a variety of emotions as you come to terms with this diagnosis and the way Alport syndrome affects your life. It is important to give yourself time and space to understand your condition and treatment options. Knowing your options and what to expect can help you manage your emotions. You are the one who makes the final decisions about your health, and your doctor is there to provide you with information and guidance. If you have any questions, need support, or need advice, talk to them.

The most important message to take home

Although Alport syndrome is a serious, lifelong genetic condition, early detection and proper management can help people live a largely normal life.

If someone in your family has these symptoms (especially blood in the urine, hearing loss), or if you experience them yourself, it's never too late to seek medical advice. With the right tests and treatment, you can minimize kidney damage and maintain your quality of life. Remember, you are not alone, and doctors and your loved ones are there to help you.

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