Alport Syndrome

Definition and EtiologyTop

Alport syndrome (AS) is a hereditary nephropathy caused by abnormal synthesis of type IV collagen alpha chains, which leads to damage of the glomerular basement membranes. AS is most commonly X-linked (in ~80% of patients). A fully symptomatic disease occurs in men, while women are carriers or have a milder form of the disease. Other types of AS have autosomal inheritance (either autosomal recessive or autosomal dominant), occur in both sexes, and have a course similar to a milder variant of X-linked AS.

Clinical FeaturesTop

Microscopic hematuria, progressive nephritis, proteinuria, declining renal function, sensorineural deafness, and ocular manifestations are observed. End-stage renal disease (see Chronic Kidney Disease) occurs in almost all men and usually develops by their second and third decades of life. Most patients have high-frequency sensorineural hearing loss. Various ocular lesions, such as anterior lenticonus, maculopathy, corneal endothelial vesicles, and bilateral posterior subcapsular cataract can occur. Ocular or ear problems are never congenital and usually become apparent by late childhood to early adolescence.

TreatmentTop

There is no curative therapy for AS; however, a registry study identified that therapy with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs; with original evidence being available mostly for ACEIs), or both decreased proteinuria, delayed renal failure, and improved life expectancy.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to observational data and increased from low to moderate due to sibling control and effect size. Gross O, Licht C, Anders HJ, et al. Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int. 2012 Mar;81(5):494-501. doi: 10.1038/ki.2011.407. Epub 2011 Dec 14. PMID: 22166847. At present renal transplant is the only available treatment of AS.