Alport syndrome

Alport syndrome is a genetic, inherited disorder that runs in families. In a healthy kidney, nearly a million individual kidney subunits, called nephrons, filter blood through a spherical sac called the glomerulus. The glomerulus consists of a membrane, known as the glomerular basement membrane (GBM), that acts as a filtration barrier. The above figure shows a healthy GBM relative to a leaky or ruptured GBM typical of Alport syndrome patients. Healthy individuals also have a substance called collagen, of which there are several types, and in general all types provide structural support to various tissues. Type IV Collagen exists as a heterotrimer: three protein chains (α3, α3, and α3) intertwine. In Alport syndrome, mutations in the genes COL4A3, COL4A4, and COL4A5, each responsible for coding their respective protein chains, cause a dysfunctional type IV collagen, which compromises the ability of the GBM to act as a filtration barrier. As a result, the GBM becomes leaky, and substances that should have been retained in the body are lost, including blood and proteins. The kidney tissue soon becomes permanently damaged and is replaced by fibrous tissue in a process called fibrosis. Finally, the kidney becomes so damaged that kidney failure may result, causing the patient to develop end stage renal disease, or ESRD. It is important to note that Alport syndrome is a multisystem disease, as it also leads to hearing loss and ocular abnormalities. How is Alport syndrome inherite...

What is alport syndrome? Alport syndrome is an inherited genetic condition caused by a mutation in one of the genes that produces collagen, a building block of the body. Alport syndrome can cause kidney problems, hearing loss, and eye pain and vision problems. It is also sometimes associated with certain types of tumors and blood vessel problems. Alport syndrome is a rare condition that affects approximately 1/50,000 newborns. There is no cure for Alport syndrome, but close follow up with your doctor can help to reduce or prevent damage to organs like the kidneys, eyes, and ears. You should go see your primary care doctor in the next 24 hours. Diagnosis is based on having the right symptoms, genetic testing, and doing blood tests to determine kidney function. Treatment is with medications (ACE inhibitors) and referred to a nephrologist for long term management. Alport syndrome symptoms Symptoms of Alport syndrome can be categorized by urinary and kidney-related symptoms, ear, and eye symptoms, smooth muscle tumors and abnormal blood vessels. Urinary and kidney-related symptoms Urinary symptoms may be present as early as childhood, like blood in the urine, or may develop later in life, like frothy urine. • Blood in the urine: Also called hematuria, this will initially involve a small amount of blood in the urine, such that it cannot be seen with the naked eye and can only be noticed when urine is tested in a laboratory. Eventually, people with Alport Syndrome can have episo...

Alport syndrome always affects the kidneys, but it also causes some eye abnormalities in patients. These include abnormalities of the cornea, the lens and the retina. This is because kidney dysfunction in people with Alport syndrome is caused by a collagen defect in the basement membrane of the kidneys which can also be found in the ear, cornea, lens capsule and retina. Eye issues are less common in females and are rare in children. Eye issues usually develop over time as the disease progresses. These eye abnormalities can sometimes be used to diagnose individuals with Alport syndrome. It is important for individuals with Alport syndrome to have their eyes checked regularly by an ophthalmologist who is aware of the associated ocular (eye) features. Below are the most common eye conditions associated with Alport syndrome. Dot-and-fleck retinopathy Sometimes referred to as “fleck retina”, this condition involves abnormal yellowish and/or whitish flecks or dots of pigment of the retina and does not typically result in any vision abnormalities. Dot-and-fleck retinopathy is uncommon in childhood but becomes apparent at the onset of kidney failure and worsens over time in relation to the deterioration of kidney function. All males with dot-and-fleck retinopathy should be tested for Alport syndrome since it occurs in 85% of affected adult males. No treatment is necessary since this condition does not affect vision. Anterior Lenticonus This condition results in an abnormality in t...

• Overview   • • Theory   • Epidemiology • Aetiology • Case history • Diagnosis   • Approach • History and exam • Investigations • Differentials • Criteria • Screening • Management   • Approach • Treatment algorithm • Emerging • Prevention • Patient discussions • Follow up   • Monitoring • Complications • Prognosis • Resources   • Guidelines • Rare familial nephropathy due to abnormalities in type IV collagen. May be inherited in 1 of 4 patterns: X-linked, autosomal recessive, autosomal dominant or autosomal digenic. Associated with considerable clinical variability of age of onset of chronic renal failure. Frequently associated with sensorineural hearing loss. Female carriers of X-linked mutations have a significant lifetime risk of developing hypertension and renal disease. Strong genotype-phenotype correlations in X-linked Alport's syndrome have been described in male patients. Monitoring and treatment of renal disease is the main treatment. Definition Alport's syndrome is an inherited disease of the glomerular basement membrane caused by abnormalities in type IV collagen. Gubler MC. Inherited diseases of the glomerular basement membrane. Nat Clin Pract Nephrol. 2008 Jan;4(1):24-37. http://www.ncbi.nlm.nih.gov/pubmed/18094725?tool=bestpractice.com It is associated with sensorineural hearing loss, lenticonus (bulging of the lens capsule and the underlying cortex Jacobs K, Meire FM. Lenticonus. Bull Soc Belge Ophtalmol. 2000;(277):65-70. http://www.ncbi.nlm.ni...

Alport syndrome is an inherited disease that’s characterized by kidney disease, hearing loss, and eyesight problems. Alport syndrome causes kidney disease by damaging glomeruli—the tiny filters in your kidney tasked with filtering your blood. With Alport syndrome, the collagen type IV that’s found in your glomeruli, inner ear, and eyes is affected, making them unable to do their function properly. In turn, your kidneys become weak, and less and less waste is filtered from your blood. This sometimes leads to • Blood in urine (hematuria). This is the first symptom a person with Alport syndrome will have • Protein in urine (proteinuria) • High blood pressure • Swelling in the feet, ankles and eye area. Swelling is also called edema. Causes Alport syndrome is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes. These genes are responsible for the formation of a part of type IV collagen. Collagen is the major protein in your body that’s responsible for giving strength and support to your connective tissues. This collagen is found in your inner ears, and abnormalities in it can lead to sensorineural hearing loss. Type IV collagen is also important in keeping the shape of your eye lens and the normal color of your retina, and it’s the abnormalities with it that cause the eye complications associated with Alport syndrome. Males only have one X chromosome, females, on the other hand, have two X chromosomes and, accordingly, two copies of the gene, so the mutation of the gen...