Sporadic case of X-chromosomal Alport syndrome in a consanguineous family

Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematu ria and progressive nephropathy lending to renal failure. The main extraren al features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected famil ies, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who pres ented with an unusual association of obstructive uropathy and AS. Hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persis tence of symptoms after medical treatment of poststreptococcal GN and surgi cal correction of obstructive uropathy finally led to renal biopsy. The obs erved ultrastructural changes of the glomerular basement membrane were typi cal fur AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the va lue of molecular studies for genetic counselling in AS.