What is COL4A4-related Alport Syndrome?
Alport syndrome is an inherited connective-tissue disorder that can cause progressive kidney disease, abnormalities affecting the eyes, and hearing loss. There are three genes associated with Alport syndrome, and COL4A4-related Alport syndrome is caused by harmful genetic changes (mutations) in the COL4A4 gene. 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 COL4A4-related Alport syndrome is variable in severity. Some individuals have a milder disease course, while others develop a more severe disease with complications. Males with the condition have similar disease severity to females with the condition. Although the data is somewhat limited, recent studies have shown that some individuals may have a COL4A4 mutation as well as a mutation in a different gene (digenic inheritance).
The first sign of disease is often blood in the urine (hematuria) from kidney disease, which typically presents during childhood. This is usually not detectable by the naked eye, but it may be visible during periods of illness. Individuals also develop protein in the urine (proteinuria) during childhood. Kidney disease often progresses to kidney failure by early adulthood. This 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 typically a kidney transplant and/or dialysis may eventually be necessary.
COL4A4-related Alport syndrome is also associated with varying degrees of progressive hearing loss and eye abnormalities. The onset and severity of hearing loss is variable, but it is not uncommon for some degree of hearing loss to develop by adolescence. Eye abnormalities including those affecting the outer protective layer of the eye (cornea), the transparent tissue behind the iris (lens), and the the light-sensitive tissue in the back of the eye (retina) are the most common. These abnormalities may result in light sensitivity, clouding of the lens of the eye (cataracts), 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 the recessive form of Alport syndrome, COL4A3 and COL4A4, are responsible for about 20% of all cases. Alport syndrome occurs at a similar frequency amongst all ethnicities.
How is COL4A4-related Alport Syndrome treated?
Currently, there is no cure for 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 eventually develop and because the onset of kidney failure is variable, transplantation or dialysis may be required as early as the teenage years in some individuals, but is most often necessary by adulthood. Hearing aids may be required to manage hearing loss. Additionally, ophthalmologic intervention, such as cataract surgery, may be required for some affected 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 COL4A4-related Alport syndrome.
What is the prognosis for an individual with COL4A4-related Alport Syndrome?
While the prognosis of COL4A4-related Alport syndrome is variable, the vast majority of affected individuals develop kidney failure by 40 years of age. Renal transplantation and/or dialysis are typically successful as patients approach kidney failure. Complications from kidney disease may still result in a shortened life span. Hearing loss typically develops in most individuals by 40 years of age, also. Many times, the eye complications do not cause any severe visual abnormalities, although cataract surgery and/or corrective lenses may be required.