Can You Live a Normal Life With Alport Syndrome?

Alport syndrome is a multisystem disorder characterized by progressive renal failure, sensorineural deafness, and eye abnormalities. Recently, the high risk of cardiovascular pathology in people with Alport syndrome was also described.

• It is a rare disease that affects people all over the world.
• Estimates of prevalence range from 1 in 5,000 to 1 in 50,000 live births. 

Alport syndrome has no known treatment that can prevent the development of kidney failure, but an early diagnosis is crucial because there are drugs that can delay the disease's progression.

Alport syndrome is a genetic and inherited multisystem disorder that runs in families. It is also considered an inherited form of kidney inflammation (nephritis) caused by a flaw (mutation) in a gene that codes for collagen, a protein found in connective tissue. The protein on the lining of the glomeruli, which are the filters in the kidney, is affected by Alport syndrome, which can lead to kidney disease and kidney failure.

Dysfunctional type IV collagen due to a mutation in genes

• Mutations in the genes COL4A3, COL4A4, and COL4A5, which are responsible for coding their respective protein chains, cause a dysfunctional type IV collagen, which compromises the ability of the kidney's filtration barrier.
• As a result, substances that should have remained in the body, such as blood and proteins, are lost.
• The kidney tissue quickly becomes permanently damaged and is replaced by fibrous tissue in a process known as fibrosis. 
• Finally, the kidney may become so damaged that it fails, causing the person to develop the end-stage renal disease (ESRD).
• It is important to remember that Alport syndrome is a multisystem disease that causes hearing loss and ocular abnormalities due to dysfunctional type IV collagen.

Three genetic types involved in Alport syndrome

1. X-linked Alport syndrome
   • Accounts for approximately 85 percent of cases.
   • Is the most common type.
   • More severe in men than in women.
2. Autosomal recessive Alport syndrome
   • Accounts for approximately 15 percent of cases.
   • Men and women may have equally severe diseases.
3. Autosomal dominant Alport syndrome
   • Accounts for approximately one percent of cases.
   • Is the rarest type.
   • Men and women have equally severe diseases.

Different mutations in type IV collagen genes can result in a wide range of disease phenotypes. Because of the high rate of spontaneous mutation, up to 20 percent of people with Alport syndrome have no family history.

Risk factors for Alport syndrome

• Although the disorder is rare, it primarily affects men. Despite the absence of visible symptoms, women can pass on the Alport syndrome gene to their children. Men have been noted to be associated with worse severity, suggesting maternal transmittance.
• Preexisting kidney diseases, such as nephritis and glomerulonephritis.
• People with hearing loss before age 30.
• Individuals with a family history of Alport syndrome.
• Having ESRD in male relatives.
• In the United States, western states have a significantly higher rate of Alport syndrome (which is up to twofold more common in western states than other US regions).

Genetic mutations cause changes in the protein collagen, which is essential for kidney function. Collagen also protects the eyes and ears. Therefore, any change in collagen can harm the kidneys, ears, and eyes.

Initially, a person with Alport syndrome may not exhibit any symptoms. The glomeruli are gradually destroyed, resulting in blood in their urine and a decrease in the effectiveness of their kidney's ability to filter appropriately. The person experiences a general loss of kidney function and a buildup of wastes and fluids in the body.

Women with Alport syndrome typically have milder symptoms or no symptoms at all. Symptoms in men are typically more severe and worsen at a faster rate.

Common signs and symptoms of Alport syndrome

• Chronic kidney disease
  • Blood in the urine is a common feature of Alport syndrome, which can be detected using urine dipsticks as early as infancy. There may be episodes of visible hematuria in young children.
  • As the disease progresses, protein begins to appear in the urine.
  • Progressive kidney function loss can occur (as evidenced by increased serum creatinine or decreased estimated glomerular filtration rate).
• Hearing loss
  • Alport syndrome can cause hearing loss. However, not all people with Alport syndrome are affected. Hearing in Alport syndrome individuals is normal at birth.
  • Hearing loss develops gradually in afflicted people, generally when they develop proteinuria. In other cases, hearing loss is only discovered after a complete renal function.
  • Early indications may include the diminished capacity to hear high-frequency noises; this grows more severe and affects lower frequencies.
  • Hearing loss is not always complete in Alport syndrome. Once hearing loss has started, it usually worsens slowly over 10 years or more.
• Eye changes
  • Anterior lenticonus (abnormal shape of the lens) and cataracts can lead to a slow decline in vision.
  • Corneal erosion is the loss of the outer layer of the eyeball's covering, resulting in irritation, itching, redness, or impaired vision.
  • Dot-and-fleck retinopathy refers to abnormal retinal coloration. It does not cause visual difficulties, but it can aid in diagnosing Alport syndrome.
  • A macular hole is caused by thinning or a break in the macula. The macula is a region of the retina that helps sharpen and detail center vision. A macular hole causes the central vision to be clouded or distorted.
  • Swelling around the eyes.
• Leiomyomatosis
  • Symptoms usually appear in late childhood and include:
    • Dysphagia
    • Postprandial vomiting
    • Substernal or epigastric pain
    • Recurrent bronchitis
    • Dyspnea, cough, and stridor
• Other symptoms and abnormalities
  • Aortic dissection (rare)
  • Leiomyomas (which are the tumors of smooth muscle affecting the esophagus and female genital tract) may occur rarely
  • Swelling overall (including ankle, feet, and legs)
  • Symptoms of either heart failure or kidney failure can be present or develop in people with Alport syndrome
  • Hypertension
  • Pain in the chest
  • Nausea that persists all-day
  • Extreme fatigue
  • Shortness of breath
  • Weakened bones
  • In some people, there may be no symptoms at all

People with Alport syndrome can develop the end-stage renal disease between adolescence and the age of 40 years.

Alport syndrome currently has no particular treatment option. Treatment strategies for Alport syndrome involve monitoring and controlling the disease's severity and treating the symptoms.

• Hypertension
  • Blood pressure must be monitored and controlled in people with Alport syndrome.
  • Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers effectively delay disease progression and control hypertension.
• Chronic kidney diseases
  • The incidence of hematuria and proteinuria in people with Alport syndrome will eventually lead to chronic kidney disease (CKD).
  • ACE medications decrease proteinuria and the development of renal disease. They should be considered in individuals with Alport syndrome (especially youngsters) who have proteinuria with or without hypertension.
  • Proteinuria has been demonstrated to be considerably reduced when ACE inhibitors are used with spironolactone.
  • For individuals with considerable protein leaks into their urine, ACE inhibitor medication or equivalent options should now be the standard treatment protocol. When taken over a long period, this might have a significant effect on when dialysis/transplantation is required. It can sometimes mean the difference between needing it and not needing it 
  • Kidney disease must also be controlled or treated with fluid restriction, dietary changes, and other interventions.
  • Dialysis or a kidney transplant will be required if CKD progresses to end-stage renal disease.
• Eye and hearing defects
  • Although eye impairments may require surgery, hearing difficulties must be handled via the development of new skills, such as lip reading, sign language, and the use of hearing aids.
  • Hearing aids are highly required during the adolescent or young adult years to cope with hearing loss.
  • In addition, ear protection equipment should be used in noisy or loud environments.
• Genetic counseling
  • People with Alport syndrome should be given genetic counseling on how the condition is passed down to their children.
  • Education regarding the disease and counseling can both be helpful.
• Clinical trials
  • Alport syndrome cannot be treated directly since there are no specific and authorized medicines for it. However, clinical trials are presently underway, so an approved treatment may be available shortly.
  • Gene therapy has been widely explored. Gene therapy may one day be able to treat Alport syndrome by replacing the COL4A5 gene. But getting it to the podocytes in the glomerulus, which ordinarily make type IV collagen in the glomerular basement membrane, is challenging.
  • Researchers are presently working on novel ways to diagnose and treat Alport syndrome. People with Alport syndrome and their families can discuss joining these clinical trials with their doctor as a way to improve their chances of a better future.

Excessive or insufficient protein consumption may put a person with Alport syndrome at risk, necessitating careful monitoring. Complications such as anemia, malnutrition, osteodystrophy, and acidosis should be continuously monitored, as should any danger from heart disease, vascular disease, or diabetes. It should be noted that the earlier the treatment, the better the outcomes.

Because Alport syndrome is inherited, there is no way to prevent it. However, early diagnosis and a skilled multidisciplinary medical team can help slow the progression of the disease and improve the quality of life.

People with Alport syndrome should always keep a detailed list of symptoms and discuss it with their doctor.

Ways to reduce the complications of Alport syndrome

• Blood pressure control
  • For people with Alport syndrome, it is critical to control blood pressure.
  • It aids in preserving kidneys and lowers the risk of cardiovascular disease (heart disease or stroke).
  • Consult the doctor to determine the ideal blood pressure. 
  • A healthier lifestyle with dietary changes such as quitting smoking, maintaining a healthy weight, exercising regularly, eating a low-salt diet, having fluid restriction, and having protein intake checked can all help slow the disease.
• Awareness
  • Awareness of the risk factors for Alport syndrome, such as a family history of the disease, can allow the condition to be detected at an early stage.
  • If the condition is detected early, it may be possible to slow the progression of kidney disease by using blood pressure medications.
  • If a patient has a family history of Alport syndrome, they should talk to their doctor or a genetic counselor before starting a family. 
  • To ensure that the Alport gene is not passed on, in vitro fertilization can be combined with genetic testing.
• Others
  • Reduce exposure to loud noise and avoid earphones as much as possible.
  • Regular blood and urine tests are also performed to assess kidney function, and the patient may be offered treatments if they develop high blood pressure, anemia, or bone weakness.
  • Avoid the use of nonsteroidal anti-inflammatory drugs.
  • Regular checkups with a physician to rule out or avoid complications

Over the last decade, significant advances in genetic technologies have increased the availability of genetic testing for Alport syndrome. This is now the first-line investigation for making a diagnosis. Furthermore, there has been a significant increase in the development of new treatments for Alport syndrome over the last five years, with several new therapies now in clinical trials. While there are currently no formally approved treatments for Alport syndrome, this may not be too far away.