Spectrum of collagen type IV nephropathies: From thin basement membrane nephropathy to Alport syndrome

Alport syndrome and thin basement membrane nephropathy are common causes of persistent familial haematuria. They are associated with various mutations in type IV collagen genes. Mutations in genes, coding for alpha5 chain of collagen IV, cause X-linked Alport syndrome, whereas mutations in genes for alpha3 and alpha4 chains can cause the autosomal recessive and autosomal dominant type of Alport syndrome or benign familial haematuria with thin basement membrane nephropathy. In view of the wide spectrum of phenotypes, an exact diagnosis is sometimes difficult to achieve. Few studies of genotype-phenotype correlations in Alport syndrome have shown that various types of mutations may be a significant predictor of the severity of disease. Histopathologic findings in Alport syndrome vary from normal kidney to nonspecific focal segmental and global glomerular sclerosis with characteristic ultrastructural finding of thickening and splitting of the glomerular basement membrane. Thin basement membrane nephropathy is characterized by diffuse thinning of the glomerular basement membrane on an ultrastructural level, while by light microscopy glomeruli are mostly unremarkable. Because of present limitations of mutation screening techniques, kidney biopsy with mandatory ultrastructural analysis and immunohistochemistry examination for type IV collagen alpha chains remains a standard approach for establishing diagnosis and determining the mode of transmission of the disease.