Alport Syndrome: Definition, Causes, Symptoms, Diagnosis, Treatment and Prevention

This disease was first described in British medical literature in the early years of the 20th century.

In 1927, Dr. Cecil Alport published an article describing the association of kidney disease and deafness in affected individuals.

Many additional cases were described in the literature and the disorder was named after Dr. Alport in 1961.

Alport syndrome is a rare inherited genetic condition caused by a mutation in one of the genes that makes collagen , the body’s building block.

Alport syndrome can cause kidney problems, hearing loss, eye pain, and vision problems.

It is also sometimes associated with certain types of tumors and blood vessel problems.

Alport syndrome is a rare condition that affects approximately 1 / 50,000 newborns.

There is no cure for Alport syndrome, but close follow-up with your doctor can help reduce or prevent damage to organs such as the kidneys, eyes, and ears.

Alport syndrome is also known as:

  • Hereditary nephritis.
  • Hereditary congenital hematuria.
  • Hematuria-nephropathy-deafness syndrome.
  • Hemorrhagic familial nephritis.
  • Hereditary hematuria syndrome.

Subdivisions of Alport Syndrome

  • Autosomal dominant Alport syndrome (ADAS).
  • Autosomal recessive Alport syndrome (ARAS).
  • COL4A3-related nephropathy.
  • COL4A4-related nephropathy.
  • COL4A5-related nephropathy.
  • Síndrome de Alport X-Linked (XLAS).

Causes of Alport Syndrome

Alport syndrome is caused by mutations in specific genes. Genes provide instructions for creating proteins that play critical roles in many functions in the body.

When a gene mutation occurs, the protein product can be defective, inefficient, or absent. Depending on the functions of the particular protein, this can affect many organ systems in the body.

Alport syndrome is a genetic disease caused by a mutation in certain genes that make proteins called type IV collagen, which are important components of tissue found in the kidneys, ear, and eye.

There are a few ways that Alport syndrome runs in families:

  • Autosomal dominant inheritance: In autosomal dominant Alport syndrome, only one side of the family must have the mutation for Alport syndrome to pass it on to children.
  • Autosomal recessive inheritance: In autosomal recessive Alport syndrome, both sides of the family owe the mutation for Alport syndrome to pass on to children.
  • X-linked inheritance: In X-linked Alport syndrome, the disease is usually passed from a mother who has the Alport syndrome mutation to her child.

Symptoms of Alport syndrome

The onset, symptoms, progression, and severity of Alport syndrome can vary greatly from person to person, in part due to the specific subtype and genetic mutation present.

Some people may have a mild, progressive form of the disorder, while others may have an earlier onset of serious complications.

The symptoms of Alport syndrome can be classified according to symptoms related to urine and kidneys, ear and eye symptoms, smooth muscle tumors, and abnormal blood vessels.

Urinary and kidney symptoms

Urinary symptoms can present as early as childhood, such as blood in the urine, or they can develop later in life, such as foamy urine.

Blood in the urine

Also called hematuria, it initially involves a small amount of blood in the urine, such that it cannot be seen with the naked eye and can only be noticed when the urine is analyzed in a laboratory.

Eventually, people with Alport syndrome can have episodes of visible blood in the urine that usually occur before the age of 10. Bloody urine is painless.

Foamy urine

It usually occurs at a later age (16 to 35 years) and occurs because long-term damage to the kidneys causes protein to be lost in the urine.

High blood pressure and swelling of the body

This occurs at a later age, with the advancement of the disease, due to prolonged kidney damage that prevents the kidneys from carrying out their functions of production and excretion of urine normally.

Auditory and visual symptoms

Symptoms related to the ears and eyes can develop, including:

Hearing loss on both sides

Most people with Alport syndrome develop progressive hearing loss (sensorineural deafness in both ears, which begins with an inability to hear high-pitched sounds, but then progresses to unable to hear conversational speech.

Hearing loss will begin during childhood and worsen during adulthood.

Blurred vision or changes

Vision changes or blurred vision are caused by the development of cataracts, which is when the normally clear lens of the eye becomes cloudy and does not let as much light into the eye.

Anterior lenticone is a condition in which the lenses of the eyes are abnormally shaped, specifically the lens protrudes into the space (anterior chamber) behind the cornea.

The anterior lenticone can result in the need for glasses and sometimes leads to cataract formation.

The retina, which is the light-sensitive and nerve-rich membrane that lines the back of the eyes, can also be affected, usually by pigmentary changes caused by the development of superficially located yellow or white spots on the retina. These changes do not appear to affect vision.

Eye pain

The cornea, which is the transparent (transparent) outer layer of the eyes, can also be affected, although the specific abnormalities can vary.

The effects on the cornea can be slowly progressive. Recurrent corneal erosions can occur in which the outermost layer of the cornea (epithelium) does not adhere (adhere) to the eye properly.

Recurrent corneal erosions can cause severe eye pain or discomfort, abnormal sensitivity to light (photophobia), blurred vision, and the sensation of a foreign body (such as dirt or an eyelash) in the eye.

Smooth muscle tumors

A small percentage of people with Alport syndrome can develop smooth muscle tumors known as leiomyomas. Details include:

  • Location: These tumors can occur in the respiratory system, the gastrointestinal system, or the female reproductive system.
  • They are not cancerous.
  • They are usually painless.
  • Inhibitor: These tumors can interfere with normal functions, such as breathing, digestion, and fertility.

Abnormal blood vessels

Additional symptoms can occur in certain individuals with Alport syndrome.

In a small number of men, aneurysms of the chest or abdominal parts of the aorta, the main artery that carry blood from the heart, have developed.

Aneurysms occur when the walls of the blood vessels swell or bulge outward, which could rupture and cause bleeding within the body.

Diagnosis

Diagnosis is based on having the correct symptoms, genetic testing, and blood tests to determine kidney function.

Treatment is with medications (angiotensin converting enzyme inhibitors) and the patient is referred to a nephrologist for long-term treatment.

If you have any symptoms of Alport syndrome, such as blood in the urine, swelling of the body, hearing loss, eye pain or blurred vision, you should see your doctor.

The doctor may order tests to determine if the person has Alport syndrome.

If any member of the family has been diagnosed with Alport syndrome, a doctor should be consulted. He or she may order tests to see if you have the gene mutation that causes Alport syndrome.

Treatment and prevention options for Alport syndrome

Alport syndrome is a chronic condition that cannot be cured. Therefore, treatment focuses on regularly monitoring organ damage and managing any damage that occurs.

Specific treatments include seeing your doctor regularly, medications to decrease kidney damage, lifestyle adjustments and other support medications, dialysis, kidney transplantation, eye treatments, and hearing aids.

Once you have been diagnosed with Alport syndrome, or if your doctor suspects that you may have Alport syndrome, you should see your doctor at least once a year, to:

  • Examine the urine: This is to look for blood or protein, which may indicate that damage is occurring in the kidneys.
    Make additional recommendations: You may be recommended to follow up with a nephrologist (kidney physician) and consult a genetic counselor [8].

Medicines to slow the progression of kidney damage

If you have signs that suggest kidney damage, your doctor may recommend starting medications that slow the progression of kidney damage. These include:

  • Lisinopril (Prinivil).
  • Enalapril (Vasotec).
  • Ramipril (altace).
  • Losartán (cozaar).

If kidney damage occurs to the point where you begin to experience high blood pressure or swelling of the body, probably due to an imbalance of minerals in the blood, the doctor may recommend various medications and lifestyle changes to alleviate the symptoms. . These include:

  • Diuretics: such as furosemide (Lasix), which will increase the amount of urine you produce.
  • Diet: Limit the salt, potassium, and phosphate you eat.
  • Sodium bicarbonate (Neut): used to maintain a balance of acid and base levels
  • Calcium or vitamin D: to help maintain healthy bones.

Dialysis

If sufficient damage occurs to the kidneys and the kidneys are unable to perform their normal function, the doctor may recommend that dialysis be started, which is a treatment that performs the function of the kidneys. Dialysis is usually required until a kidney transplant can be performed.

There are two main forms of dialysis:

  • Peritoneal dialysis: A tube is placed in the abdomen and fluid is exchanged through a membrane in the abdomen.
  • Hemodialysis: A tube is placed into a blood vessel in the arm and fluid is exchanged in a machine attached to the tube.

Kidney transplant

The best long-term treatment for a kidney damaged by Alport syndrome is a kidney transplant.

This surgery replaces the kidney with a healthy one from a donor. After kidney transplantation, Alport syndrome will not recur in the donor kidney.

Eye treatments or surgery

If Alport Syndrome causes damage to the eyes resulting in eye pain or blurred vision, the doctor may refer the patient to an ophthalmologist, who can assess whether he or she would benefit from eye treatment or surgery.

Possible treatments include:

  • Eye drops.
  • The use of protective contact lenses.
  • Surgery to remove cataracts.
  • Surgery to repair damage to the back of the eye.

Earphones

If Alport syndrome causes hearing loss, your doctor may recommend the use of hearing aids.