COL4A4-related Alport syndrome
What is COL4A4-related Alport Syndrome?
Alport syndrome is a genetic condition characterized by progressive kidney disease, hearing loss, and abnormalities affecting the eyes. Alport syndrome can be inherited in an X-linked or autosomal recessive manner. COL4A4-related Alport syndrome is inherited in an autosomal recessive manner. The presentation of autosomal recessive Alport syndrome is variable in severity; some individuals have a milder disease course, while others develop more severe disease with complications. Disease severity is similar amongst males and females with autosomal recessive Alport syndrome.
Blood in the urine is often the first sign of kidney disease and typically presents during childhood. This is usually not detectable by the naked eye, but may be visible during periods of illness such as a cold or flu. Individuals also develop protein in the urine during childhood. Kidney disease often progresses to kidney failure by early adulthood. Kidney failure is associated with a variety of symptoms including: high blood pressure, fatigue, poor appetite, swelling of legs and feet, and frequent urination. Medications may delay the progression of kidney failure, but for the most part, either a kidney transplant and/or dialysis is eventually necessary.
Autosomal recessive Alport syndrome is also associated with varying degrees of progressive hearing loss. The onset and severity of hearing loss is variable, but it is not uncommon for some degree of hearing loss to develop by adolescence.
Individuals may also develop eye abnormalities. Specific problems with the lens, retina and cornea are the most common and may result in light sensitivity, cataract formation, and blurred vision. Glasses are sometimes required to correct vision.
How common is COL4A4-related Alport Syndrome?
Collectively, all forms of Alport syndrome are estimated to occur in approximately 1 in 50,000 live births. The two genes associated with autosomal recessive Alport syndrome, the COL4A3 and the COL4A4 genes, are responsible for about 15% of all cases of Alport syndrome, with an estimated incidence of 1 in 350,000 births. Autosomal recessive Alport syndrome occurs at a similar frequency amongst all ethnicities.
How is COL4A4-related Alport Syndrome treated?
Currently, there is no cure for autosomal recessive Alport syndrome. However, treatments are available to address many of the associated symptoms. Medications are used to treat high blood pressure, reduce protein in the urine, and slow the progression of kidney disease. However, kidney failure will develop eventually in individuals with autosomal recessive Alport syndrome. Because the onset of kidney failure is variable, transplantation or dialysis may be required as early as the teenage years, but most often is necessary by adulthood.
Hearing aids may be required to treat hearing loss. Additionally, ophthalmologic intervention, such as cataract surgery, may be required for some individuals.
A multidisciplinary team of physicians, including: nephrologists, audiologists, ophthalmologists and other healthcare professionals will need to be involved in the ongoing treatment and management of individuals with autosomal recessive Alport syndrome.
What is the prognosis for a person with COL4A4-related Alport Syndrome?
While the prognosis of autosomal recessive Alport syndrome is variable, the vast majority of individuals develop kidney failure by 40 years of age. Renal transplantation and/or dialysis are typically successful as patients are approaching kidney failure. Although, complications from kidney disease may still result in a shortened life span. Hearing loss develops in the vast majority of individuals by 40 years. Many times, the eye complications associated with autosomal recessive Alport syndrome do not cause any severe visual abnormalities; although, cataract surgery and/or corrective lenses may be required.