Alport Syndrome

General Medical Guideline
Last modified
12 March 2020

Alport syndrome is characterized by progressive renal failure, hearing loss, and ocular abnormalities.

The diagnosis of Alport syndrome is suspected when a person has glomerular hematuria or renal failure and a family history of Alport syndrome or renal failure without another obvious cause. The earliest sign of GBM filter dysfunction is hematuria followed by albuminuria and subsequent nonselective proteinuria in increasing magnitude. These individuals should undergo audiometry, an ophthalmologic examination, and, preferably, renal biopsy for GBM ultrastructure, collagen IV composition, and an assessment of the damage. The diagnosis of Alport syndrome is likely when there are glomerular hematuria and a family history of Alport syndrome with no other cause for the hematuria (erythrocytes in urine).

Although angiotensin-converting enzyme (ACE inhibitor) inhibition is effective in Alport syndrome patients for slowing progression to end-stage renal disease, it is neither a cure nor an adequate long-term protector.

Kidney

Alport syndrome is the second commonest monogenic cause of renal failure after autosomal dominant polycystic kidney disease.

Lack of collagen-α3α4α5(IV) changes the glomerular basement membrane (GBM) morphologically and functionally, rendering it leaky to albumin and other plasma proteins. Filtered albumin has been suggested to be a cause of the glomerular and tubular injuries observed at advanced stages of Alport syndrome. It is important to note that albuminuria does not always appear to be injurious. Despite heavy proteinuria, minimal change disease and some cases of membranous nephropathy are not associated with significant tubulointerstitial injury, glomerulosclerosis, or deterioration of kidney function.

Mechanical stress, due to the less elastic membrane and hypertension, interferes with integrin-mediated podocyte–GBM adhesion. Proteinuria occurs when urinary levels exceed tubular reabsorption rates and initiate tubule-interstitial fibrosis.

Currently, there is no specific therapy for Alport syndrome. The treatment with angiotensin-converting enzyme (ACE) inhibitors delays renal failure progression by reducing intraglomerular hypertension, proteinuria, and fibrosis.

Although experiences vary, the first signs or symptoms of Alport syndrome are blood and/or protein in their urine. Sometimes this is picked up whilst visiting the GP for something routine or unrelated.

Hearing The collagen make-up of the basement membranes of the cochleas (inner ears) is abnormal in people with Alport syndrome. A bilateral sensorineural hearing loss is often one of the first symptoms of Alport syndrome. It is never present at birth but often begins to manifest itself by late childhood or early adolescence, usually before kidney failure begins. A person with this type of hearing loss finds it difficult to hear and understand speech or interpret sounds, especially over background noise or when the speaker mumbles. Not all families with Alport syndrome will experience hearing loss.

Eye

Abnormalities of the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. The demonstration of lenticonus is diagnostic for Alport syndrome. Anterior lenticonus is present in 50% of men, but not women, with an X-linked disease, where it is associated with early-onset renal failure and peri-macular retinopathy. Lenticonus is common in both men and women with autosomal recessive inheritance, and therefore, women with Alport syndrome and lenticonus are likely to have a recessive disease.

In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce a visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure.

2015, J Savige

 

Rare Condition

Alport Syndrome

Alport syndrome is a hereditary renal disease, glomerulonephritis, resulting in renal failure. In addition, there is often (sensorineural) deafness and a congenital anomaly of the eye,...

Diseases
More info
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386265/