Clinical scenario: hematuria | +ve family history | deafness
An 11-year-old boy is referred for evaluation of persistent microscopic hematuria, detected on three separate occasions over the past year. He is normotensive and has normal renal function, but his urine protein-to-creatinine ratio is mildly elevated. His mother has persistent microscopic hematuria, and a maternal uncle developed end-stage kidney disease at the age of 28 years. On further questioning, the boy reports difficulty hearing his teacher in a noisy classroom over the past several months. Audiometry confirms bilateral high-frequency sensorineural hearing loss.
What is the most likely diagnosis?
A. Alport syndrome
B. IgA nephropathy
C. Membranoproliferative glomerulonephritis
D. Post-infectious glomerulonephritis
E. Thin basement membrane nephropathy
Correct answer & Explanation:
Correct Answer: B. Alport syndrome
Explanation: Alport syndrome
Alport syndrome is an inherited disorder caused by mutations in type IV collagen genes (COL4A3, COL4A4, or COL4A5), resulting in abnormalities of the glomerular basement membrane, cochlea, and ocular lens.
The classic triad consists of:
- Persistent microscopic hematuria progressing to proteinuria and chronic kidney disease
- Sensorineural hearing loss (typically high-frequency)
- Ocular abnormalities, especially anterior lenticonus, which is highly characteristic
The X-linked form (COL4A5 mutation) accounts for approximately 80–85% of cases. A history of affected maternal male relatives strongly suggests X-linked inheritance.
Why the other options are incorrect
- A. IgA nephropathy: Usually presents with recurrent episodes of gross hematuria following upper respiratory infections and is not associated with hearing loss or ocular abnormalities.
- C. Thin basement membrane nephropathy: Causes isolated microscopic hematuria with an excellent prognosis and does not cause hearing or ocular abnormalities.
- D. Post-infectious glomerulonephritis: Presents with acute nephritic syndrome after streptococcal infection, not progressive familial hematuria.
- E. Membranoproliferative glomerulonephritis: Typically presents with nephritic or nephrotic syndrome and hypocomplementemia without hearing or ocular involvement.
Learning Point
Features highly suggestive of Alport syndrome include:
- Persistent familial microscopic hematuria
- Progressive proteinuria and chronic kidney disease
- High-frequency sensorineural hearing loss
- Anterior lenticonus (virtually pathognomonic)
- Family history of early renal failure, particularly in maternal male relatives (X-linked disease)
Reference:
- KDIGO Clinical Practice Guideline for the Management of Inherited Kidney Diseases
- Nelson Textbook of Pediatrics, 22nd Edition
- KDIGO 2021 Glomerular Disease Guideline
