Alport syndrome

Abstract

 Alport syndrome (AS) is a hereditary disorder that generally runs a progressive course. It usually presents in children as haematuria and proteinuria associated with neurosensory deafness and progresses to end-stage renal failure (ESRF). The median renal survival rate for male X-linked AS (XLAS) cases is<25 years. Characteristic alterations of the glomerular basement membrane (GBM) are observable with electron microscopy (EM). AS is characterized by irregular thinning and thickening of the GBM as well as replication of the lamina densa, which produces a laminated appearance or basket-weave pattern. When these changes are diffuse, a diagnosis of AS can be made. AS is genetically heterogeneous and X-linked, with both autosomal dominant and autosomal recessive modes of inheritance. However, <90% of AS cases show X-linked inheritance, caused by mutations in the COL4A5 gene, which encodes the α5 chain, a type IV collagen. The α5 chain is expressed in the GBM, Bowman's capsule (BC) and epidermal basement membrane (EBM). In cases with typical male XLAS, immunohistochemical analysis shows a complete loss of the α5 chain in the GBM, BC and EBM, whereas typical female cases show segmental loss with a pattern known as mosaicism.