Is nephrocalcinosis seen in Alport syndrome?

Nephrocalcinosis in Alport Syndrome

Nephrocalcinosis is not a characteristic feature of Alport syndrome. While Alport syndrome is characterized by progressive kidney disease, the pathological hallmark is abnormalities in the glomerular basement membrane, not calcium deposits in the renal tubules.

Pathophysiological Differences

Alport syndrome is primarily a disorder of type IV collagen in basement membranes, particularly affecting:

• Glomerular basement membrane (causing hematuria and progressive renal failure)
• Cochlear basement membrane (causing sensorineural hearing loss)
• Ocular basement membranes (causing ocular abnormalities)

The key pathological findings in Alport syndrome include:

• Abnormal glomerular basement membrane structure visible on electron microscopy
• Thinning, thickening, and splitting of the glomerular basement membrane
• Absence or abnormal expression of type IV collagen chains (α3, α4, α5)

Conditions Associated with Nephrocalcinosis

Nephrocalcinosis is actually a characteristic feature of other renal disorders, including:

• Bartter syndrome types 1 and 2, where hypercalciuria with subsequent nephrocalcinosis typically occurs after 1-2 months of life 1
• Hypophosphataemia and nephrocalcinosis (NPHLOP1) associated with SLC34A1 mutations 1
• Fanconi renotubular syndrome 2 (FRTS2) 1

Diagnostic Approach

The diagnosis of Alport syndrome relies on:

1. Clinical features (hematuria, progressive renal failure, hearing loss, ocular abnormalities)
2. Family history (X-linked dominant in 85% of cases, autosomal recessive or dominant in 15%)
3. Renal biopsy with:
   • Electron microscopy showing characteristic basement membrane abnormalities
   • Immunohistology for α3(IV) and α5(IV) collagen chains 2
4. Genetic testing for mutations in:
   • COL4A5 gene (X-linked Alport syndrome)
   • COL4A3 and COL4A4 genes (autosomal forms) 3

Clinical Implications

Understanding the correct pathophysiology is crucial because:

1. The treatment approaches differ between conditions with nephrocalcinosis (like Bartter syndrome) and Alport syndrome
2. Prognosis and monitoring strategies vary significantly
3. Genetic counseling implications differ based on the inheritance pattern

Common Pitfalls to Avoid

• Misdiagnosing Alport syndrome based on the presence of nephrocalcinosis
• Failing to perform appropriate genetic testing when Alport syndrome is suspected
• Confusing the pathophysiology of basement membrane disorders with disorders of calcium metabolism
• Not recognizing that Bartter syndrome, not Alport syndrome, is characterized by nephrocalcinosis 1, 4

In summary, nephrocalcinosis should prompt consideration of conditions like Bartter syndrome, while Alport syndrome should be suspected in patients with hematuria, progressive renal failure, and often hearing loss and ocular abnormalities.