Introduction:
Alport syndrome is an inherited disorder that affects the kidneys, ears, and eyes. Dr. Cecil Alport first described it in 1927. He established the association between kidney disease and ear abnormalities. It is found to occur in one in 50,000 births. It mainly affects males, while females of the same family are carriers of this syndrome, either with mild symptoms or no symptoms (asymptomatic).
What Is Alport Syndrome?
Alport syndrome, or hereditary nephritis, is a genetic disorder that mainly affects the tiny filtering units of the kidneys, and it becomes difficult to remove the waste and excess water from the body. Patients with Alport syndrome also develop ear and eye abnormalities.
What Causes Alport Syndrome?
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The leading cause of Alport syndrome is changes or alterations (mutation) in the genes. The genes are responsible for specific proteins involved in the normal functioning of the cells of the body organs. Therefore genetic mutations cause various systemic abnormalities.
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COL4A3, COL4A4, and COL4A5 genes are responsible for a specific protein called type IV collagen that is important for maintaining the typical structure and function of kidneys, ears, and eyes. The mutation of COL4A3, COL4A4, and COL4A5 occurs in Alport syndrome leading to abnormal functioning of kidneys, ears, and eyes.
What Are the Types of Alport Syndrome?
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X-linked Alport syndrome (XLAS) is the most common type caused by mutations in the COL4A5 gene. TheX chromosome is affected by this type. Males show severe kidney abnormalities while females have milder symptoms.
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Autosomal recessive Alport syndrome (ARAS) is caused by changes in the COL4A3 or the COL4A4 genes. It occurs when the child acquires the altered gene from both the father and mother.
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Autosomal dominant Alport syndrome (ADAS) occurs if any of the COL4A3 genes or the COL4A4 gene is affected. It happens if the child acquires anyone abnormal gene from either the father or mother.
What Are the Symptoms of Alport Syndrome?
The various clinical features of Alport syndrome are as follows:
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Kidney Abnormalities: The first sign of Alport syndrome is blood in urine which is visible only under microscopic examination (microscopic hematuria). It is common among males and females. In some patients, the blood in the urine is visible for a few days. The other findings include excessive albumin (albuminuria) and other proteins in the urine. In later stages of the disease, the kidney gets affected severely, leading to hypertension, fatigue, swelling around the eyes, ankles, and feet, increased thirst, frequent urination, joint pain, etc.
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Ear Abnormalities: The hearing is diminished in early childhood; however, it progresses to complete hearing loss of both ears (sensorineural deafness) by age 40. It occurs due to impaired transmission of sound waves from the inner ear to the brain. Males are affected mainly by complete hearing loss than females.
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Eye Abnormalities: The parts of the eyes like the cornea, lens, and retina are severely affected.
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A condition called anterior lenticonus is the bulging of the lens more forward that requires the use of glasses. In addition, it sometimes leads to lens clouding (cataracts).
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The eye's inner layer (retina) sends visual images to the brain and is pigmented with yellow or white dots. The vision is not impaired in most cases. But thinning the retina in a few patients leads to holes that affect normal vision.
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The eye's outer transparent layer (cornea) does not adhere properly to the eye, leading to eye pain, blurred vision, increased sensitivity to light (photophobia), etc. In a few others, swelling of the layer of the cornea occurs, leading to a condition called posterior polymorphous corneal dystrophy. It affects the eyes and causes the sensation of dirt in the eye, photophobia, and impaired vision.
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Other findings include abnormal bulging and rupturing of arteries of the heart.
How to Diagnose Alport Syndrome?
The following methods diagnose the clinical features of Alport syndrome:
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A urine examination is done to identify the presence of blood and to detect the amount of albumin and other proteins.
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Examination of the ear using audiometry testto identify the intensity of sound heard and other hearing problems.
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Ophthalmologic (eye) examination is done to detect the abnormalities in various layers of the eye.
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A kidney biopsy is a procedure of removing tissue from the kidney to study under a microscope. It detects the abnormalities in the glomeruli of the kidney.
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Prenatal diagnosis is made by removing and studying little fluid surrounding the fetus in the mother's womb, suspected of Alport syndrome.
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The doctor orders a blood test to detect the kidneys' glomerular filtration rate (GFR). It will determine the amount of blood filtered by the glomeruli, which is essential in finding the normal functioning of kidneys.
What Is the Differential Diagnosis?
The diseases that are similar to Alport syndrome are as follows:
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AMME complex is a rare disorder with features like facial abnormalities, intellectual disability, abnormal red blood cells, and Alport syndrome symptoms.
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Thin basement membrane nephropathy (TBMN) is another disease that causes hematuria, but no other kidney abnormalities are detected.
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Polycystic kidney disease (PKD) is characterized by developing multiple fluid-filled sacs (cysts) within the kidney, leading to its function deterioration.
How to Treat Alport Syndrome?
Pharmacological Management:
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Angiotensin-converting enzyme (ACE) inhibitors like Lisinopril are used to delay the progression of kidney disease. The daily dose of ACE inhibitors should not exceed 80 mg.
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Angiotensin receptor blockers (ARBs) like Losartan with a maximum dose of 100 mg daily are suggested if the patient is intolerant to Lisinopril. It is found to reduce the amount of protein excreted in the urine. In addition, an increase in the dose can decline the kidneys' function and increase potassium levels. Therefore the patient is advised to consume more water and other fluids while taking such drugs.
Procedural Management:
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Dialysis is a procedure done to improve the function of the kidneys, like removing the waste products and normalizing blood pressure. It is done by diverting the blood from the body to a machine that helps filtrate the fluids.
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Kidney transplant has also shown promising results in treating patients with end-stage kidney disease.
Conclusion:
Although Alport syndrome causes various deformities at an early age, the progression of the symptoms is controlled with early diagnosis and appropriate management.
