Alport Syndrome

Question 1

What is Alpert syndrome?

Answer 1

Genetic disorder that is characterised by glomerulonephritis, often in combination with sensorineural hearing loss and sometimes eye abnormalities

Question 2

What is the aetiology behind Alport syndrome?

Answer 2

Usually X linked
Can also be autosomal recessive or autosomal dominant
Tends to be more severe in males

Question 3

What is the pathophysiology?

Answer 3

Genetic defect of type 4 collagen chains (component of basement membrane of kidneys, eyes and cochlea) -> kidney damage (glomerulonephritis), sensorineural hearing loss, and ocular abnormalities

Question 4

What are the clinical features of alport syndrome?

Answer 4

Age of onset changes the clinical features
Often asymptomatic
Initially intermittent gross Hematuria

As glomerular damage progresses, symptoms of nephritic syndrome and chronic kidney diseases occur (usually leads to ESRD) between 16-35 years of age

Sensorineural hearing loss
Ocular findings - retinopathy, anterior lenticonus (congenital conical elevation of the anterior or posterior pole of the crystalline lens in the eye)

Question 5

What is the diagnosis for alport syndrome?

Answer 5

Lab test - urinalysis - best initial test - signs of nephritic syndrome eg Hematuria, minor proteinuria.BUN and creatinine to assess severity of renal disease

Skin biopsy - confirmatory test, shows absence of collagen type 4 alpha 5 chains

Kidney biopsy - light microscopy - mesangial cell proliferation and sclerosis. Electron microscopy - splitting and alternating irregular thickening and thinning of the glomerular basement membrane. Immunostaining - absence of type 4 collagen alpha 3, alpha 4 and or alpha 5 chains in basement membrane

Molecular genetic testing - cans confirm and distinguish types

Question 6

What is the treatment for alport syndrome?

Answer 6

Monitor renal function regularly
In patients with proteinuria: ACE inhibitors/angiotensin II receptor blockers
In patients with renal failure: See “Treatment” in “Chronic kidney disease” (e.g., sodium restriction, diuretics).
Kidney transplant
The only definitive treatment of Alport syndrome
Complication: Goodpasture disease can occur due to newly developed collagen type IV antigens following a kidney transplant. [6]
Hearing aids in patients with hearing loss
Consider ocular surgery in patients with lenticonus