Alport Syndrome
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Direct answer
Alport syndrome is an inherited disorder of type IV collagen that causes persistent haematuria, progressive kidney disease and sensorineural hearing loss. The commonest form is X-linked, caused by COL4A5 mutations, and affected males often reach end-stage kidney disease in young adulthood. Anterior lenticonus and retinal flecks support the diagnosis, and ACE inhibitors slow progression of proteinuria.
What you must remember
- Genetics: X-linked COL4A5 is the most common form; autosomal recessive COL4A3 or COL4A4 and autosomal dominant forms also occur.
- Clinical triad: persistent haematuria, progressive proteinuria with kidney failure, and sensorineural deafness, usually high frequency first.
- Eye findings: anterior lenticonus, dot-fleck retinopathy and macular changes.
- Electron microscopy: thinning and thickening of the glomerular basement membrane with splitting and a basket-weave pattern.
- Immunostaining: absence of the collagen IV alpha 5 chain in skin or kidney supports the X-linked form.
- Sex difference: males with X-linked disease progress faster; carrier females may have milder, variable disease.
- Treatment: ACE inhibitors or ARBs for proteinuria and blood pressure; transplantation for end-stage disease.
- Family screening: first-degree relatives should be screened with urine tests and renal function.
Recognising the inherited pattern
A 9-year-old boy has persistent microscopic haematuria, a family history of kidney failure in his maternal uncles, and a hearing test that shows high-frequency loss. The table below separates the common inheritance patterns, which matter for counselling and prognosis.
| Inheritance | Gene | Typical course |
|---|---|---|
| X-linked | COL4A5 | Males progress to kidney failure in young adulthood |
| Autosomal recessive | COL4A3 or COL4A4 | Early progression in both sexes |
| Autosomal dominant | COL4A3 or COL4A4 | Milder, more variable course |
The family history and sex of affected relatives guide which gene to test. Genetic confirmation is increasingly used alongside biopsy findings.
Male relatives are usually the most informative, since X-linked disease progresses faster in males and carrier females may have milder, variable disease. Screening first-degree relatives with urine tests and renal function covers both sexes. Eye and ear findings are checked alongside the urine in clinic, since they are part of the clinical triad and are easy to miss.
Where the exam tries to catch you
Alport questions often mix renal, auditory and ocular clues in one vignette.
- Trap: attributing haematuria with deafness to glomerulonephritis alone Correct: Alport syndrome links haematuria with sensorineural deafness and eye findings, so look for them deliberately.
- Trap: assuming heterozygous females are unaffected Correct: carrier females can have haematuria and later kidney disease, though usually milder.
- Trap: labelling Alport syndrome as thin basement membrane disease Correct: thin basement membrane disease is benign, whereas Alport shows lamellation and carries a risk of kidney failure.
- Trap: treating the kidneys without considering the eyes and ears Correct: audiology and ophthalmology review are part of the diagnosis and ongoing care.
Frequently asked questions
Which gene is mutated in X-linked Alport syndrome?
The COL4A5 gene is mutated in X-linked Alport syndrome, which is the most common form. It encodes the alpha 5 chain of type IV collagen, which is needed for normal glomerular and cochlear basement membranes.
Which extrarenal features support a diagnosis of Alport syndrome?
Sensorineural hearing loss, anterior lenticonus and dot-fleck retinopathy support a diagnosis of Alport syndrome. A family history of haematuria, deafness or kidney failure in male relatives adds further weight to the diagnosis.
Why does Alport syndrome differ from thin basement membrane disease?
Alport syndrome differs from thin basement membrane disease because it shows lamellated basement membrane changes and a risk of progressive kidney failure. Thin basement membrane disease causes uniform thinning of the membrane, is usually benign, and does not cause hearing loss.
Which drugs slow kidney progression in Alport syndrome?
ACE inhibitors or ARBs slow kidney progression in Alport syndrome by reducing proteinuria and controlling blood pressure. They are started early, often once proteinuria is detected, and continued under specialist supervision.
Which kidney biopsy finding is characteristic of Alport syndrome?
Electron microscopy showing thinning and thickening of the glomerular basement membrane with splitting, a basket-weave pattern, is characteristic of Alport syndrome. Absence of the collagen IV alpha 5 chain on immunostaining supports the diagnosis.