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ALPORT SYNDROME
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WHAT IS ALPORT SYNDROME?
Alport Syndrome is a genetic disorder which causes problems with type IV collagen formation in the body. It leads to a form of hereditary nephritis, which is estimated to affect at least 1 in 5,000 individuals. Nephritis is a general term used to describe diseases that cause swelling or inflammation of the kidneys. Alport syndrome can also cause hearing loss and vision problems, as type IV collagen is also important in the lens of our eyes and in the inner ears. As the genetic disorder is generally located on the X‐chromosome, men are usually more severely affected than women. Each kidney contains up to one million nephrons, which are the working units of the kidneys. Inside the nephrons are tiny sets of looping blood vessels or capillaries. They are called glomeruli and act as filters. Type IV collagen is essential for the normal structure and function of each glomerulus. Alport Syndrome causes thinning of the collagen‐containing membranes and also scarring, which reduces their ability to filter waste and extra fluid from the blood. HOW IS ALPORT SYNDROME INHERITED?
The three genetic forms of Alport Syndrome are: 
XLAS (X‐linked Alport Syndrome) – The most common form where one of the parents carries a faulty gene on one of their X chromosomes, one of the chromosomes determining a person’s sex. XLAS accounts for 80% to 85% of Alport Syndrome cases and results from mutations of the alpha‐5 chain type IV collagen (gene COL4A5). 
ARAS (autosomal recessive Alport Syndrome) – Both parents carry the faulty gene on one of their chromosomes. This form accounts for 10% to 15% of the cases and is caused by mutations in the alpha‐3 or alpha‐4 chains (genes COL4A3 or COL4A4). 
ADAS (autosomal dominant Alport Syndrome) – One parent carries the faulty gene on one of their chromosomes. Rare form that accounts for about 5% of the cases and is caused by mutations in the alpha‐3 or alpha‐4 chains (genes COL4A3 or COL4A4). Alport Syndrome Page 2/4
XLAS: When the mother is the carrier of the mutation, her chance of transmitting it to her children is 50% with each pregnancy as she has two X chromosomes, one affected and one normal. Male offspring who inherit the mutation will have the disease as they have only one X chromosome and a Y chromosome. Female offspring have two X chromosomes, so the normal X chromosome buffers the effect of the mutated X chromosome. Therefore, daughters who inherit the mutation will be carriers like their mothers. Sons who inherit the mutation will pass the disease on to all of their daughters and to none of their sons, because they will give their mutated X chromosome to their daughters and their normal Y chromosome to their sons. ARAS: Autosomal recessive disorders result when both copies of a gene are defective. Typically, each parent of a child with a recessive condition passes a mutant gene to the child. The parents only have one mutation in one of the chromosomes, so they can be asymptomatic (have no symptoms) or have some hematuria (blood in the urine). However, it is unlikely that they will have progression of the disease. When each parent carries the defective gene, there is a 25% probability with every pregnancy that the child will have ARAS. ADAS: A mutated gene exists on one of the numbered chromosomes. There are two copies of every chromosome, and the dominant mutated gene will override the working gene. This form of the disease progresses more slowly than other forms. Each child of an affected parent has a 50% chance of inheriting the mutation. Some people with Alport Syndrome do not have a family history of this disease. In these cases, it occurs as a result of a new genetic mutation. HOW IS ALPORT SYNDROME DIAGNOSED?
When a case of Alport Syndrome is found, it is important for all family members to be checked for the condition, and this is usually initially done with a simple urine dipstick test. In the majority of cases of Alport Syndrome, there will be some microscopic haematuria and proteinuria (blood and protein in the urine that is not visible to the naked eye) that can be detected. Unless there is a known family history of the condition, a diagnosis of Alport Syndrome may not be made until serious kidney problems develop. It is very important for any young boys or men presenting with hearing loss to have their kidney function checked to exclude Alport Syndrome, as hearing problems usually occur at a much earlier stage than kidney problems. If possible, it is also important for female carriers of the condition to be diagnosed before starting a family. This is so that they may consider preventing Alport Syndrome in their own children by using in vitro fertilisation (IVF) techniques. The symptoms of Alport Syndrome are similar to those of other kidney diseases and often the diagnosis relies on careful evaluation of the patient’s clinical features, family history and results of tissue biopsies or genetic testing through a genetic counselling service. Genetic tests can be carried out using blood or tissue samples. A kidney biopsy may also be used to confirm the diagnosis. A small piece of kidney tissue is examined under a microscope for changes to the basement membrane structure. Microscope examination of a skin biopsy can also be useful as the type IV collagen alpha‐5 chain is normally present in the skin. A diagnosis of Alport Syndrome can also be confirmed with lens or retinal abnormalities, as there are some changes that do not occur in any other condition. WHAT ARE THE COMPLICATIONS OF ALPORT SYNDROME?
The first sign of kidney damage is blood (haematuria) and then protein (proteinuria) in the urine:  Blood in the urine This is always present in young male children but may be absent in young females. Blood in the urine may not always be visible but microscopic amounts can be detected using a urinary dipstick. Alport Syndrome Page 3/4
 Protein in the urine Protein may be present in the urine of teenagers and young adults. Large amounts of protein in the urine can cause fluid retention and swelling of body parts, e.g. ankles, wrists, face. If males do not have blood and/or protein in their urine after 10 yrs of age, they are unlikely to have Alport Syndrome. See the ‘Albuminuria’ and ‘Blood in the Urine’ fact sheets for more information. Other common complications include:  Kidney disease With increasing age, boys develop other signs of kidney damage, including high blood pressure, reduced appetite and tiredness.  Kidney failure Alport Syndrome always causes kidney failure in males but uncommonly and much later in life in females. Males develop kidney failure any time between 15 and 50 years of age.  Deafness Alport Syndrome can be linked with a slow loss of hearing and may be a clue to diagnosis. Not everyone will suffer from deafness, but those who do generally develop it by the time they are teenagers. Loss of hearing in girls tends to be milder than in boys. Hearing loss seems to worsen roughly in step with increasing kidney problems.  Vision problems Vision problems can also be linked to Alport Syndrome. It can produce oddly shaped lens, lens changes, cataracts or changes to the retina in the back of the eye. These changes can be evident to an ophthalmologist even if the individual has not noted any visual impairment. See ‘Chronic Kidney Disease’ as well as ‘Heart Disease and Chronic Kidney Disease’ fact sheets for more information. HOW IS ALPORT SYNDROME TREATED?
There is currently no treatment that can stop or reverse the effects of Alport Syndrome. The treatment aim is to control complications and slow the progress of kidney disease:  High Blood Pressure Effective control of blood pressure is crucial. It helps to preserve kidney function and reduce the risk of cardiovascular disease. Different types of blood pressure tablets work in different ways so it is not unusual for more than one type to be prescribed. In recent years, the use of ace inhibitors or angiotensin receptor blockers has proved to be an effective treatment for high blood pressure and to help to reduce proteinuria. Healthy lifestyle choices can also help, e.g. staying at a healthy weight and being a non‐smoker.  Hearing Loss Hearing aids may be helpful. People need to protect their hearing in noisy places. Loss of hearing is likely to be permanent, so education and counselling to deal with this change and gain new communication skills may be helpful. Kidney transplantation will not improve hearing problems.  Vision Problems If there are severe problems, an intraocular lens implantation or surgery may be needed.  Dialysis and Transplantation When the kidneys fail, dialysis or transplantation is required. Transplantation is usually a successful treatment. However, it is important to make sure that a potential family member donor is not a carrier of the faulty gene. In cases where people with Alport Syndrome have the collagen gene Col4A5 missing, transplantation is not an option because their immune system rejects the new kidney. See the ‘Treatment Options’ fact sheet for more information. Alport Syndrome Page 4/4
CAN ALPORT SYNDROME BE PREVENTED?
Couples with a family history of Alport Syndrome may wish to discuss their situation with a doctor or genetic counsellor to identify any risks when starting a family. It is possible to combine IVF with genetic testing to ensure the faulty gene is not passed on. This is called ‘preimplantation genetic diagnosis’ or ‘PGD’. WHAT IS THE OUTLOOK FOR ALPORT SYNDROME?
Researchers are currently developing new methods for diagnosing Alport Syndrome and checking for mutations. Identification of faulty genes means that further investigation into the way the gene works can take place and future gene therapy for this condition becomes a possibility. Researchers are also investigating new approaches to the treatment of Alport Syndrome. WHO SHOULD I CONTACT FOR MORE INFORMATION?
The Alport Foundation of Australia is a non‐profit support group for patients and families affected by Alport Syndrome. It promotes research into the treatment of Alport Syndrome and related genetic renal diseases. Further information can be found on their website www.alport.org.au. For more information about Kidney or Urinary health, please contact our free call Kidney Health Information Service (KHIS) on 1800 454 363. Alternatively, you may wish to email [email protected] or visit our website www.kidney.org.au to access free health literature.
This is intended as a general introduction to this topic and is not meant to substitute for your doctor's or Health Professional's advice. All care is taken to ensure that the information is relevant to the reader and applicable to each state in Australia. It should be noted that Kidney Health Australia recognises that each person's experience is individual and that variations do occur in treatment and management due to personal circumstances, the health professional and the state one lives in. Should you require further information always consult your doctor or health professional. Kidney Health Australia gratefully acknowledges the valuable contribution of Alport Foundation of Australia in the development of this material. Revised April 2015 If you have a hearing or speech impairment, contact the National Relay Service on 1800 555 677 or www.relayservice.com.au. For all types of services ask for 1800 454 363.