What is Alport Syndrome ?
Alport Syndrome is a rare hereditary disease that causes glomerulonephritis, severe kidney damage and hearing loss. It may also affect the eyes, leading to various ocular manifestations such as vision problems.
The English physician Dr. Cecil A. Alport first discovered this genetic disorder in 1927. However, some people believe that British doctor William Howship Dickinson has a significant contribution in characterizing the disease.
The disorder is also known by the following names:
- Hereditary Nephritis
- Hematuria – Nephropathy – Deafness
- Hemorrhagic Familial Nephritis
- Hereditary Deafness and Nephropathy
Alport Syndrome Incidence
This disease can affect people from any country and ethnic group. One out of every fifty thousand people in America carries the defective gene responsible for Alport Syndrome. However, many of them do not show any symptoms. The manifestations of the condition are more commonly seen in men.
Alport Syndrome Causes
This is a genetic condition caused by mutations of the COL4A5, COL4A4 and COL4A3 collagen biosynthesis genes. These gene mutations prevent the assembly or production of type IV collagen network. It is a very important structural element for the formation of the basement membranes in inner ears, eyes and kidneys. The thin, sheet-like basement membranes separate and support the cells in various tissues. Collagen biosynthesis gene mutations damage the basement membranes of the kidney. As a result, the kidney cannot filter the waste materials from the blood which allows blood and protein to mix with urine.
The mutations of the type IV collagen genes in the basement membranes of the kidney gradually cause scarring of the kidneys. It may even lead to kidney damage in some people having this disease. Progression of Hereditary Nephritis in a person causes the basement membrane to thicken, giving it an appearance that resembles “basket-weave”. Alterations in the structure of the mutated type IV collagen molecules can be noticed through single molecule computational analyses.
Alport Syndrome Inheritance Pattern
The disease can follow three different modes of inheritance depending on the gene mutations:
X-Linked Pattern
In the majority of cases, the condition follows an x-linked inheritance pattern and is caused by COL4A5 gene mutation. In males, only one abnormal copy of COL4A5 gene can lead to severe Alport syndrome as males have only one X chromosome. This explains why the disease leads to serious kidney damage in most male patients. In females, one copy of mutated COL4A5 gene causes some symptoms like blood in the urine; but, it rarely causes kidney failure.
Autosomal Recessive Pattern
Hereditary Nephritis is inherited in autosomal recessive pattern when two copies of the COL4A4 or COL4A3 gene, which is located on the chromosome 2, undergoes mutation. Generally, the parents of children having autosomal recessive Hereditary Nephritis do not have the disease but are carriers of the abnormal gene.
Autosomal Dominant Pattern
Around 5% of the total patients having Alport Syndrome inherit it in an autosomal dominant pattern. Its clinical features resemble those inherited in the x-linked pattern. However, the deterioration of the renal functions occurs at a slower rate when the disorder is inherited in this pattern.
Alport Syndrome Symptoms
The disease is characterized by various renal problems, eye abnormalities and ear problems.
Symptoms of Renal Damage
The main symptoms of renal damage include:
- Change in the color of urine
- Accumulation of waste products in the kidney due to the damage of the basement membrane of the kidney
- Various urinary infections
- Swelling of the hands and legs or even Anasarca
- Presence of excessive amounts of protein in the urine (Proteinuria)
- Increased blood pressure due to kidney damage
Symptoms of Sensorineural Deafness
Alport Syndrome causes hearing impairments. Boys are more likely suffer from hearing loss due to the disorder compared to girls. It can even cause permanent deafness in male patients.
Symptoms of Eye Problems
The ocular manifestations of the genetic condition involve:
- Changes in the vision
- Cataract formation (in some cases)
- Bulging of lens capsule or Anterior Lenticonus
Alport Syndrome Prevention
Couples with a family history of Hereditary Nephritis should consider genetic counseling to determine the chances of having a baby with the disease. Gene reviews and genetic testing are quite useful for this purpose. Pre-pregnancy screening and newborn screening helps to understand if a child has the syndrome.
Alport Syndrome Diagnosis
Doctors study the family history of patients before performing various diagnostic tests. The following tests are used for diagnosing Hereditary Nephritis:
- Skin biopsy analysis
- Kidney biopsy analysis
- Renal ultrasound
- Vision and hearing evaluation and testing
- Computed Tomography scan or CT scan
- Magnetic Resonance Imaging or MRI
- Electron Microscopy
Alport Syndrome Differential Diagnosis
The following conditions are characterized by symptoms similar to those of Hereditary Nephritis:
- Acute Post-streptococcal Glomerulonephritis
- Multicystic Renal Dysplasia
- Medullary Cystic Disease
- Polycystic Kidney Disease
- Nephritis
- Nail-Patella Syndrome
Doctors should not confuse the signs of any of the above disorders with those of Alport Syndrome.
Alport Syndrome Treatment
The treatment of this disease often depends on the nature and severity of the symptoms. It is very important that a Nephrologist examines the patient regularly to identify any signs of kidney disease at an early stage. Regular vision and hearing evaluation is also required. Following are the main treatment methods used to cure Hereditary Nephritis:
Medications
Nephrologists often prescribe certain blood pressure medications that prevent the production and actions of angiotensin II. These medications are used as they have been proved to delay the progression of various kidney diseases and they do not usually cause any major side effects. Animal studies show that ACE or angiotensin-converting enzyme inhibitors help to reduce the levels of protein in the urine (Proteinuria) and also slow down the progression of kidney diseases. The following ACE inhibitors are used for treating Alport Syndrome:
- Fosinopril (Monopril)
- Enalapril (Vasotec)
- Quinapril (Accupril)
- Lisinopril (Zestril, Prinivil)
ARBs or Angiotensin Receptor Blockers are sometimes used for treating individuals suffering from Proteinuria because these medications can slow down the progression of kidney damage and failure. Angiotensin Receptor Blockers used for the treatment of this disease include:
- Candesartan (Atacand)
- Losartan (Cozaar)
Both ARBs and ACE inhibitors should be prescribed to Alport Syndrome patients suffering from Proteinuria. They may or may not have high blood pressure.
Monitoring
The blood pressure of the patients should be controlled and monitored regularly in addition to treating them with ARBs and/or ACE inhibitors. Tests used for monitoring the blood pressure include Creatinine, 24-hour urinary protein and serum chemistry. Generally, patients without any problems with the functioning of their kidneys should be monitored once every year, while those with minor kidney problems require to be monitored once in six months. Individuals having advanced kidney damage should be monitored once in every one to three months.
The vision and hearing of the Hereditary Nephritis patients also require regular monitoring every 1 to 2 years beginning when they are 6 years to 7 years old. Doctors often prescribe hearing aids to patients with serious hearing loss.
Kidney Transplant
Alport Syndrome patients with ESRD or End Stage Renal Disease require kidney dialysis or renal transplant. Kidney transplantation is often used for treating the disorder successfully. However, it is important to evaluate related kidney donors properly as this is a hereditary condition. Individuals with mutated type IV collagen gene should not be kidney donors.
According to some recent studies, various surgeries such as stem cell therapies, bone marrow transplantation and gene therapies are also useful for treating Alport Syndrome.
Alport Syndrome Complications
This genetic disease can cause complete hearing loss, blindness and kidney failure. ACE inhibitors and ARB medications used for treating this syndrome do not generally cause any serious side effects. However, they may cause certain side effects in some individuals. Common side effects of ACE inhibitors include:
- Cough
- Low blood pressure
- Higher blood potassium levels
- Headache
- Dizziness
- Weakness
- Drowsiness
- Loss of taste
- Rash
Severe side effects of these medications include allergic reactions, kidney failure, reduced levels of white blood cells and Angioedema (swelling of tissues). However, these side effects are very rare and affect few people.
ARBs may also cause cough in some people. Liver failure, kidney failure, decreased white blood cells, allergic reactions and Angioedema are the most severe side effects of ARBs. However these side effects occur very rarely.
Alport Syndrome Prognosis
The prognosis is generally positive in women. Proper treatment cures the condition completely in women as they do not generally show any severe symptoms.
In male patients, the outcome depends on the level of kidney damage and the treatment. Early diagnosis and proper treatment help to control the symptoms and kidney damage in men. However, in many cases, male patients develop various visual difficulties, deafness and kidney failure by the time they become 50 years old.
Alport Syndrome and Pregnancy
It can cause various complications during pregnancy. The growth of the fetus may be restricted if the symptoms of Hereditary Nephritis progress rapidly, causing kidney damage and other problems. It can lead to various birth defects and abnormal birth weight of the newborn baby.
Taking ACE inhibitors and ARBs to treat this condition during pregnancy can also harm an unborn child and cause many birth defects.
Alport Syndrome Life Expectancy
Women with Hereditary Nephritis have a normal life span as they do not generally develop the severe symptoms of the disorder. Timely diagnosis, proper treatment and regular monitoring help men with this disorder to live a long and happy life.
Alport Syndrome Support Groups
Many foundations and support groups help Alport Syndrome patients and their families to fight the disease by providing proper guidelines. The contact details of some of these support groups have been furnished here:
National Kidney Foundation
30 East 33rd Street
New York, 10016
Fax: (212)689-9261
Tel: (212)889-2210
Email: info@kidney.org
Website: http://www.kidney.org
American Kidney Fund, Inc.
6110 Executive Boulevard
Suite No. 1010
Rockville, MD 20852
USA
Fax: (301)881-0898
Tel: (301)881-3052
Email: mdemelo@kidneyfund.org
Website: http://www.kidneyfund.org
Madisons Foundation
PO Box 241956
Los Angeles, California 90024
Fax: (310)264-4766
Tel: (310)264-0826
Email: getinfo@madisonsfoundation.org
Website: http://www.madisonsfoundation.org/
Alport Syndrome Pictures
The following images display how the disorder affects the appearance of the eyes of patients.
Picture 1 – Alport Syndrome
Picture 2 – Alport Syndrome Image
Alport Syndrome may turn life threatening if left untreated. However, proper treatment allows an individual suffering from the disorder to live a relatively normal and happy life.