By Dr Liji Thomas, MD
Alport syndrome (AS) is a disease caused by abnormal collagen formation, which occurs in about 1 in 50,000 newborns. It affects both males and females, but can be inherited only from females in the majority of cases. It affects the kidneys, and inevitably results in progressive renal fibrosis, and end-stage renal failure.
Symptoms and signs
Patients with Alport syndrome may present with:
- High-colored urine;
- Swelling of the legs, or around the eyes, or of the whole body;
- Visual and hearing loss, more commonly in male patients; and
- Blood passed in urine, sometimes only after an infection of the upper respiratory tract, or exercise.
On examination, there may be:
- Eye changes,
- Retinal lesions,
- Bulging of the lens (lenticonus), and
- A high blood pressure.
- Renal failure,
- Chronic kidney disease,
- Permanent hearing loss, and
- Visual loss
Genetic basis for Alport syndrome
The disease is due to mutations in the COL4A5, COL4A3 or COL4A44 genes which code for type IV collagen synthesis and assembly. This defect causes immature glomerular basement membrane to persist in the kidneys, leading to failure of blood filtration. The occurrence of hematuria and proteinuria is a consequence of the membrane defect, and the ultimate outcome is kidney damage.
The genetic basis of the disease makes family genetic testing necessary. Alport syndrome is inherited mostly as an X-linked disorder, but in some cases it is autosomal recessive, and in very rare cases autosomal dominant. Early detection of the mutation may help to prevent or delay the onset of renal failure, and to detect carrier mothers, who are at a higher risk of renal complications themselves.
Diagnosis and treatment
The features of Alport syndrome are:
- Hematuria persisting for at least a year,
- Renal failure,
- Sensorineural hearing loss, likely to be permanent,
- Lenticonus and retinal flecks,
- Lamellation of the glomerular basement membrane due to an abnormal type IV collagen, and
- The presence of mutations of the COL4A5, COL4A3 or COL4A44 genes.
Females may never have any symptoms other than hematuria, while affected males usually show the full range of disease.
Genetic testing is the gold standard for diagnosis of the condition. Each of these mutations points to a distinct mode of inheritance, as well as a quantified risk for the early onset of renal failure, and for the occurrence of extra renal manifestations.
Other tests include audiometry, renal function tests, renal biopsy and urine analysis.
Management involves genetic testing and counseling, and measures to protect the kidneys, the hearing and the vision. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARB) and aldosterone inhibitors are all useful in the management of proteinuria in this condition. Lens replacement is often necessary.
Last Updated: Feb 4, 2016