[Alport syndrome: Hereditary nephropathy associated with mutations in genes coding for type IV collagen chains].
Alport syndrome is an inherited disorder characterized by the association of a progressive haematuric nephropathy with ultrastructural abnormalities of the glomerular basement membranes, a progressive sensorineural hearing loss and sometimes ocular involvement. Its incidence is less than 1 per 5000 individuals and the disease is the cause of about 2% of end stage renal disease in Europe and the United States. Alport syndrome is clinically and genetically heterogeneous. It is related to mutations in the genes encoding one of three chains, α3, α4 α5 of type IV collagen, the main component of basement membranes, expressed in the glomerular basement membrane. COL4A5 mutations are associated with X-linked Alport syndrome, which represents 80 to 85% of cases and is more severe in boys than in girls. Mutations in COL4A3 or COL4A4 are associated with autosomal Alport syndrome. The expression of collagen chains in skin and kidney basement membranes allows for the diagnosis and characterization of the mode of transmission in most patients. It is necessary to diagnose this syndrome because its family involvement, its severity, and the importance of genetic counseling. Angiotensin blockers are increasingly prescribed in proteinuric patients. Prospective studies are needed to assess the effectiveness of these treatments on proteinuria and progression of kidney failure, and to specify indications. Animal studies have shown the potential value of different molecules (protease inhibitors, chemokine receptor blockers, transforming growth factor-β1 inhibitors, hydroxy-methyl-coenzyme A reductase inhibitors, bone morphogenetic protein-7 inhibitors), hematopoietic stem cells, and of a anti-micro-RNA.
Service de néphrologie pédiatrique, centre de référence des maladies rénales héréditaires de l'enfant et de l'adulte (Marhéa), hôpital Necker-Enfants-malades, 149, rue de Sèvres, 75743 Paris cedex 15, France. Electronic address: laurence.heidet@aphp.fr.
Laurence
L
Heidet
Inserm U1163 Laboratory of Hereditary Kidney Diseases, Imagine Institute, 24, boulevard du Montparnasse, 75015 Paris, France.
Marie-Claire
MC
Gubler
D015415:Biomarkers / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics*; D016572:Cyclosporine / Q000627:therapeutic use*; D003937:Diagnosis, Differential; D018450:Disease Progression; D005817:Genetic Counseling; D050533:Glomerular Basement Membrane / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009154:Mutation; D009394:Nephritis, Hereditary / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
D015415:Biomarkers; D024141:Collagen Type IV; D007166:Immunosuppressive Agents; D016572:Cyclosporine
Alport syndrome; COL4A3; COL4A4; COL4A5; COL4A6; Collagen IV; Collagène IV; Diffuse oesophageal leiomyomatosis; Glomerular basement membrane; Léiomyomatose œsophagienne diffuse; Macrothrombocytopathy; Membrane basale glomérulaire; Syndrome d’Alport; Thrombopathie à plaquettes géantes