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An inherited disease characterised by glomerular nephropathy with hematuria, progressing to end-stage renal disease, associated with sensorineural deafness. It involves a structural defect of type IV collagen, which is a normal component of the glomeral basal membrane.
ORPHA:63Classification level: Disorder
Prevalence is estimated at 1/50 000.
Ocular abnormalities are present in 1/3 of the cases (anterior lenticonus, corneal lesions). Sensorineural deafness is linked to cochlear involvement. Extrarenal involvement can also be observed, such as thrombopenia and leiomatosis (see this term). Mutations in the COL4A5 gene, localised on chromosome Xq22 and coding for the alpha 5 chain of type IV collagen, are responsible for the most frequent form of the disease. Male patients are severely affected and present with microhematuria very early in life (around the age of 3.5 years for boys and 9 years for girls), followed by proteinuria and progression to end-stage renal disease before the age of 40. Progression is milder in most female patients. Mutations in COL4A3 and COL4A4 genes, which map to chromosome 2, are responsible for the less frequent (15%) autosomal recessive form of AS. In this autosomal form of AS, the disease is equally severe for female and male patients. A few rare cases of autosomal dominant forms have been reported.
The diagnosis of the disease is based on family history, clinical signs and the results of renal biopsy, showing abnormalities of the glomerular basal membrane by electronic microscopy examination. The study of the binding of antibodies directed against the alpha 3, alpha 4 and alpha 5 chains of collagen IV in the kidney and skin also allows the diagnosis to be made.
Management and treatment
Adult patients retain some hearing capacity, although some of them require a hearing aid. Both hemodialysis and peritoneal dialysis are used to treat patients with end-stage renal failure. Kidney transplantation in AS patients is usually successful, but some authors have reported that about 10% of transplanted patients develop nephritis in the graft.