Key Points
Disease summary:
Alport syndrome is a hereditary glomerular disease caused by mutations in the genes encoding type IV collagen. It is often associated with hearing loss and ocular abnormalities.
The most common form of inheritance is X-linked. Classically the affected males present with asymptomatic hematuria in the first decade of life. With advancing age they develop proteinuria, renal insufficiency, and hypertension. They typically progress to end-stage renal disease (ESRD). Males without hematuria in the first decade of life are unlikely to be affected.
Hereditary basis:
The most common mode of transmission of Alport syndrome is X-linked and a small percentage is autosomal recessive.
Differential diagnosis:
It is important to distinguish Alport syndrome from other causes of hematuria. These include other glomerulonephritides (IgA nephropathy, MPGN, PSGN), tubulointerstitial diseases (acute pyelonephritis, sickle cell anemia), urinary tract (structural anomalies, hypercalciuria), and vascular anomalies (nut cracker syndrome).
The evaluation includes a thorough history including family history, physical examination, evaluation of the urinary sediments (to ascertain if glomerular hematuria), urine and blood studies, renal ultrasound, audiometry, and ophthalmologic examination. Evaluation of urine sediment of family members may aid in the diagnosis. Once the family history, laboratory evaluation, audiometry, and ophthalmologic examination point toward Alport syndrome, skin and renal biopsy can confirm the diagnoses. Genetic testing when available may be the test of choice.
| System | Manifestation | Incidencemur_ch146rf1,mur_ch146rf2,mur_ch146rf3 |
|---|---|---|
Renal | Hematuria | XLAS males 100% XLAS heterozygous females ~90% Males and females with ARAS 100% |
Proteinuria, hypertension, and renal insufficiency | XLAS males—all ARAS males and females—all with advancing age | |
Progression to ESRD | XLAS Males—60% by 30 years, 90% by 40 years XLAS heterozygous females—12% by 40 years, 40% by 80 years ARAS males and females all by 20 to 30 years | |
Auditory system | Sensorineural hearing loss | XLAS males 80% by 15 years XLAS heterozygous females 20% by 15 years |
Vision | Anterior lenticonus—conical protrusion on the anterior aspect of the lens due to thinning of the lens capsule is pathognomonic of Alport syndrome. Retinal changes include white or yellow granulations around the fovea. In the cornea, changes that can be seen include posterior polymorphous dystrophy and recurrent corneal erosions. | XLAS males 30% to 40% |
Diagnostic Criteria and Clinical Characteristics
The suspicion for Alport syndrome is high if the proband and other family members meet at least three of the following:
Positive family history of macro- or microscopic hematuria or chronic renal failure
Electron microscopic evidence of AS on renal biopsy
Characteristic ophthalmic signs (anterior lenticonus and macular flecks)
Sensorineural deafness
These criteria strongly suggest Alport syndrome, for a firm diagnosis genetic testing may be required.
Clinical features of a typical male with X-linked Alport syndrome include persistent hematuria with progression to ESRD, hearing loss, and ocular abnormalities (Table 146-1
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