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ALPORT SYNDROME

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ALPORT SYNDROME

Alport syndrome is a rare genetic disorder of the kidney marked by progressive kidney disease involving the basement of the kidney membrane and frequently involving the cochlea as well as the eye.

  • Alport syndrome affects the kidney by attacking the glomeruli that help with the filtering process.
  • The condition affects about 1 in 500,000 newborns.
  • Males and females are not equally affected, while males tend to be more badly affected, females only have mild symptoms
  • It is the second most common cause of chronic kidney disease (CKD) after polycystic kidney disease, a condition in which fluid-filled sacs develop in the kidney impairing kidney function.
  • In CKD, the kidney loses its functions progressively and does not effectively filter out wastes from the body.
  • Without treatment, the condition will result in end-stage kidney disease

CAUSES

The condition is caused by mutations in the COL4A3, COL4A4, and COL4A5. These genes give instruction responsible for making one component of a protein called type IV collagen, which is a major part of the basement membranes present in all tissues including the kidneys, inner ear, and eyes.

Type IV collagen plays an important role in the glomeruli found in the kidney. Glomeruli are clusters of blood vessels that remove water and waste products from the blood and creates urine. Mutations in these genes result in abnormalities of the type 1V collagen in the glomeruli. This leads to an improper filtering of blood by the kidneys, allowing protein and blood to pass down into the urine. Over time, scarring of the kidney occurs, eventually leading to kidney failure in the majority of people suffering from the condition.

In the inner ear structures especially the organ of Corti which transforms sound waves into nerve impulses that the brain can process, type IV collagen also plays an important role. Mutations in these genes often result in abnormal inner ear function.

Type IV collagen also plays an important role in maintaining the shape of the lens and the normal color of the retina. Any alteration that disrupts the functionality of this protein can result in eye problems.

Alport syndrome is a genetic condition inherited in three different patterns: the X-linked recessive pattern (XLAS), autosomal recessive pattern (ARAS), and autosomal dominant form (ADAS).

Note that the AS refers to Alport Syndrome

About 80% of this condition is inherited in the X-linked pattern due to mutations in the COL4A5 gene. A condition is considered X-linked if the gene involved is located on the X-chromosome. In this type, the male typically has kidney failure and more severe symptoms than female. This is because males usually have one X- chromosome and one altered copy of the COL4A5 is sufficient to cause the symptoms. In females with two chromosomes, a mutation in one copy of the COL4AS causes mild symptoms, although some female experience severe symptoms.

About 15% of this condition is inherited in an autosomal recessive pattern due to mutations in the COL4A3 or COL4A4. Autosomal recessive occurs when two abnormal genes are inherited, one from each parent. This means that both parents must carry the defective gene and transmit the gene to the child for the child to have the condition.

About 5% of cases are inherited in an autosomal dominant pattern due to mutations in the COL4A3 and COL4A4 genes.

SYMPTOMS

Symptoms may differ from person to person

  • Blood in the urine (hematuria)
  • Hearing loss
  • An abnormal pigment of the retina (dot-and-fleck retinopathy)
  • Protein in the urine (proteinuria)
  • Joint pain (osteodystrophy)
  • Swelling (edema)
  • Damage to the macula that allows for central vision
  • Cone-shaped lens (anterior lenticonus)
  • Bone weakening

DIAGNOSIS AND TREATMENT

The condition is suspected based on family history or symptoms of the condition.

To make a diagnosis, the doctor may recommend a kidney biopsy to check for abnormalities of the glomeruli cells as well as test for the presence of the type IV collagen, this is usually absent in an individual with the condition.

Tests may be ordered to measure the amount of blood and protein in the urine.

An eye doctor may carry out eye examination to check for symptoms such as anterior lenticonus).

If the condition is suspected after diagnosis, genetic testing may be used to confirm the diagnosis and check the pattern of inheritance.

TREATMENT

No specific treatment exists. Treatment options aim to monitor and control the progression of the condition and treat the symptoms.

Treatment option may include:

  • Ace inhibitor to slow down the progression of kidney disease.
  • Surgical repair of the eyes.
  • Loss of hearing may be permanent, hearing aids may be recommended.
  • Counseling and education to be able to cope with the condition
  • Learning sign languages or lip reading may be advantageous.

If the condition has resulted in end-stage kidney failure, dialysis, and kidney transplant may be needed.