What is Alport Syndrome?
Alport syndrome occurs in 1 out of 50,000 newborns. Alport syndrome symptoms are much more common in males than in females.
Alport syndrome is a primary basement membrane disorder arising from mutations in the genes coding for alpha-3, alpha-4 and alpha-5 chains of the type IV collagen protein family. These alpha chains are normally located in various basement membranes of the kidney, inner ears and eyes and the genetic abnormalities characteristic of this disease result in abnormalities in the basement membranes at these sites resulting in the clinical features of the disease.
The disease can be transmitted in heterogeneous patterns depending on the gene involved. The most common one is an X chromosome linked pattern where the disease is passed from unaffected females (carriers) to their male children and usually involves the COL4A5 gene. Females who have an X-chromosome with the affected gene may show some symptoms but will not have the full blown disease. The syndrome is caused by mutations in the genes COL4A3 and COL4A4, which are usually inherited in either an autosomal dominant or autosomal recessive pattern.
The classic presentation of the disease is seen in X-linked disease and the presentation is quite similar in those with autosomal recessive patterns of inheritance. These would include glomerular disease (hematuria and proteinuria) which progress to end stage renal disease, eye abnormalities (eg anterior lenticonus), sensorineural hearing loss and a family history of hematuria (blood in the urine) associated with renal failure and deafness. Patients with autosomal dominant disease exhibit a more gradual loss of renal function.
What are the Symptoms of Alport Syndrome?Glomeruli are small tufts in the kidney that contain blood vessels; they collect wastes from the blood and create urine.
Mutations in the above-said genes result in abnormalities in the glomeruli, which result in blood and proteins being passed into the urine. Eventually scarring and kidney failure occur in these individuals.
The same collagen is vital for maintaining the shape of the lens in the eye and the color of the retina too. An abnormality in the collagen results in out-of-shape lenses (anterior lenticonus) and abnormal coloration of certain light-sensitive tissue in the retina.
Common Symptoms Include:
- Swelling in the ankle, feet, leg, eyes
- Blood in the urine (which is initially microscopic but episodes of gross hematuria are not uncommon)
- Abnormal urine color
- Decreased vision / complete loss of vision (mostly in males)
- Flank pain
- Overall swelling of the body
- Loss of hearing (mostly in males)
The condition worsens to end-stage renal disease (ESRD) early on in the affected personís life - between adolescence and 40 years.
In some cases, there are no symptoms. In women who are carriers of the disease, the symptoms are milder while in men they are much graver.
How Do You Diagnose Alport Syndrome?Specific gene analysis has been recommended in a patient who has met at least two clinical diagnostic criteria for Alport syndrome.
The following are the criteria for clinically diagnosing Alport syndrome:
- Family history of nephritis (inflammation of the kidneys)
- Persistent hematuria (blood in the urine)
- Gradual bilateral sensorineural hearing loss
- Presence of glomerular abnormalities
- Presence of ocular lesions
- Diffuse leiomyomatosis of esophagus / female genitalia or both (Leiomyomata are benign smooth muscle tumors)
- Eye examination for screening changes in the eye
- Checking for BP
- Audiometry for hearing-related problems
- Blood tests - Complete blood count (CBC) and serum creatinine
- Kidney biopsy and skin biopsy
- DNA analysis to detect gene mutation
How Do You Treat Alport Syndrome?There is no specific treatment for Alport syndrome currently available. The primary goal of therapy is to control the rate of progression of the disease and allay the symptoms.
It is vital to strictly monitor and control blood pressure in these patients. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can effectively do this job and slow the progress of the disease.
The presence of hematuria and proteinuria will eventually result in chronic kidney disease (CKD) in patients with Alport syndrome and this needs to be controlled or treated with limited intake of fluids, changes in diet and other methods. When CKD eventually progresses to end-stage kidney disease, dialysis or kidney transplant will be required.
Eye problems may require surgery, while hearing problems need to be addressed with learning new skills such as lip reading and sign language, and by wearing hear aids. Protection devices may also be worn to protect the ear in a noisy environment.
Genetic counseling should be provided to the patients on how the disease is transmitted to the offspring.
Women who are carriers usually have a normal lifespan while males usually develop complications by the time they are in their teens and in some rare cases by the fifth decade.