Alport syndrome is a rare genetic disease that affects the kidneys. This condition is caused by problems with three genes that control how parts of the eyes, kidneys, and ears are formed. Alport syndrome almost always results in kidney disease and may also result in eye and hearing problems.
While there is no cure for Alport syndrome, there are treatments such as ACE inhibitors and ARBs that can help protect the kidneys and keep them working longer. In this blog, we break down the causes, symptoms, and available treatment options for Alport syndrome.
Key Points
- Alport Syndrome is a genetic condition that is characterized by progressive kidney damage and deformities of the eye and inner ear.
- The severity of Alport syndrome depends on the type of mutation and how severely it affects the building of the basement membrane.
- Treatments, such as ACE inhibitors and ARBs, can help protect and keep the kidneys working longer.
What is Alport Syndrome?
Alport syndrome is a rare genetic disorder (inherited condition) that causes deformities in the glomerular basement membrane. This can result in kidney disease and lead to kidney failure. In the United States, Alport syndrome is estimated to affect 1 in 5,000 people and occurs in 3% of children who have chronic kidney disease.
What Causes Alport Syndrome?
A genetic mutation in the DNA sequence of specific genes causes Alport syndrome. In the case of Alport syndrome, the genes provide the instructions for collagen (a protein) that plays an essential role in many different functions in the body. Collagen (type IV) is a protein that helps make up part of the glomeruli (kidney filters) called the basement membrane.
The basement membrane is part of a three-layer structure that filters the blood, removing waste products, toxins, and excess water. The basement membrane also ensures that no proteins, blood cells, or other vital contents stay in the blood. When the basement membrane is damaged, it can no longer work properly, which may result in blood or protein leaking into the urine. The kidney’s ability to filter the urine and blood also decreases, which may cause complete kidney failure.
Type IV collagen is also an essential protein in the eyes and ears. Therefore, those who have Alport syndrome can also have or develop problems with their hearing and vision.
What are the Different Genetic Types of Alport Syndrome
Alport syndrome is a genetic condition, meaning that it is passed down from parent to child. There are three genetic types:
Autosomal recessive Alport syndrome (ARAS)
Autosomal recessive genetic conditions result when a child inherits an abnormal or mutated copy of the gene from each parent. A parent with an autosomal recessive trait does not show any symptoms.
In Alport syndrome, ARAS accounts for approximately 15% of all cases. The genes COL4A3 and COL4A4 reside on chromosome 2, and in ARAS, the mutation occurs in both copies of either gene. The risk is the same for the same females or males. If you have ARAS, there is a 50% chance of passing one mutated gene to your biological child and a 25% chance of passing both mutated genes to your biological child.
Autosomal dominant Alport syndrome (ADAS)
This type of Alport syndrome is caused by mutations or abnormalities in one copy of either the COL4A3 gene or the COL4A4 gene. Dominant genetic disorders result when there is a single copy of a mutated gene. This mutated gene can be inherited from either parent or can be a result of a new gene change (variant).
There is a 50% risk of passing the mutated gene to the offspring in each pregnancy. The risk is the same for both females and males. ADAS accounts for 25-35% of all Alport syndrome cases.
X-linked Alport syndrome (XLAS)
This is the most common type of Alport syndrome. X-linked (related to the X chromosome) affects about 80% of people with this disease. The X chromosome is one of the two sex chromosomes (X and Y) and where the COL4A5 gene is found.
Typically, most men have one X and one Y chromosome, with most women having two X chromosomes. As males only have one X chromosome, if they have the mutated COL4A5 gene, they may have more severe symptoms compared to females who have one mutated X chromosome and one normal X chromosome.
Men cannot pass on XLAS to their male children as they only inherit the Y chromosome. However, men can pass on their abnormal X chromosome to all their female children, resulting in Alport syndrome. Females have a 50% chance of passing on XLAS to any of their children, as one of their X chromosomes is passed on to either child regardless of sex.
Alport Syndrome Symptoms
Due to the weakened glomerular wall and damaged filters, the first symptom of Alport syndrome is typically blood in the urine. Other signs and symptoms may include:
- Hypertension (high blood pressure)
- Proteinuria (protein in the urine)
- Edema (swelling in the legs, feet, ankles, and around the eyes)
- Vision loss
- Hearing loss
- Fatigue (extreme tiredness)
- Muscle cramps
- Nausea and vomiting
Symptoms of Alport syndrome may differ per person, as they are based on gender, age, and the inherited type.
As kidney function starts to decline and chronic kidney disease (CKD) progresses to late-stage or kidney failure, symptoms may include:
- Hypertension (high blood pressure)
- Fatigue (extreme tiredness)
- Muscle cramps
- Edema (swelling in the legs, feet, ankles, and around the eyes)
- Nausea and vomiting
Symptoms of Alport syndrome may differ per person, as they are based on gender, age, and the inherited type.
How is Alport Syndrome Diagnosed?
If your healthcare provider believes (based on medical history, family history, and signs and symptoms) that you or your child have Alport syndrome, the following tests or exams will be conducted for a diagnosis to be made:
- Kidney biopsy
- Eye (ophthalmological) exam
- Urine test
- Blood test
- Hearing test
- Glomerular filtration rate (GFR)
- Genetic test
- Kidney ultrasound
Families looking at pre-implantation genetic diagnosis (PGD) or prenatal diagnosis should seek advice from a certified genetic counselor.
How is Alport Syndrome Treated?
The aim of treatment is to slow kidney damage (disease progression) and treat any symptoms. Your nephrologist and healthcare provider will provide you with the treatment options that are best suited for your needs. Treatments may include:
- Angiotensin II receptor blockers (ARBs): The medications lower blood pressure and decrease protein in the urine. They are typically used in people who poorly tolerate ACE inhibitors.
- Angiotensin-converting enzyme (ACE) inhibitors: These medications are similar to ARBs and also work to lower blood pressure and decrease the amount of protein leaking into the urine.
- Kidney-friendly diet: A low-sodium and salt diet can help lower blood pressure, helping preserve heart and kidney health.
While these treatments do not cure Alport syndrome, they can help protect the kidneys and keep them working for longer. If kidney failure is approaching, dialysis or a kidney transplant is needed. Kidney transplantation in those with Alport syndrome is typically successful and is often the preferred treatment option in the event of kidney failure.
Where can I find more information about Alport syndrome?
If you would like to know more about Alport syndrome or information about current clinical trials:
You can also talk to your nephrologist and care team about any concerns that you may have about an Alport syndrome diagnosis and what that means for your future.
Panoramic Health
Panoramic Health is placed at the forefront of kidney care innovation. By investing and partnering with sponsors and clinical research organizations (CROs), we are committed to improving patient outcomes, slowing disease progression, and ultimately improving patients’ quality of life. We also provide the latest updates in kidney care.
