Alport Syndrome Research Paper

ALPORT DISEASE

Alport syndrome is a genetic condition characterized by kidney disease, hearing loss, and eye abnormalities. People with Alport syndrome experience progressive loss of kidney function. Almost all affected individuals have blood in their urine (hematuria), which indicates abnormal functioning of the kidneys. Many people with Alport syndrome also develop high levels of protein in their urine (proteinuria). The kidneys become less able to function as this condition progresses, resulting in end-stage renal disease (ESRD). People with Alport syndrome frequently develop sensorineural hearing loss, which is caused by abnormalities of the inner ear, during late childhood or early adolescence. Affected individuals may also have misshapen

Significant hearing loss, eye abnormalities, and progressive kidney disease are more common in males with Alport syndrome than in affected females. Alport syndrome occurs in approximately 1 in 50,000 newborns. Alport syndrome can have different inheritance patterns. About 80 percent of cases are caused by mutations in the COL4A5 gene and are inherited in an X-linked pattern. This gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the COL4A5 gene in each cell is sufficient to cause kidney failure and other severe symptoms of the disorder. In females (who have two X chromosomes), a mutation in one copy of the COL4A5 gene usually only results in hematuria, but some women experience more severe symptoms. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In approximately 15 percent of cases, Alport syndrome results from mutations in both copies of the COL4A3 or COL4A4 gene and is inherited in an autosomal recessive pattern. The parents of an individual with the autosomal recessive form of this condition each have one copy of the mutated gene and are

Initially, there will be blood in urine (haematuria) only, although proteinuria (protein in the urine) may also develop. Occasionally, the proteinuria is so marked that nephrotic syndrome is diagnosed. Later, the blood pressure starts to rise and, in men, renal function declines slowly. Once the blood creatinine has reached *200 mol/l patients can be advised that a form of dialysis or a transplant will be required, on average, 16 months later. This is very roughly 50% of kidney function, which would be classed as stage three of kidney disease. Transplanted patients usually do very well, and Alport Syndrome does not recur in the transplanted kidney. However, apart from the usual risks of rejection, there is a small risk of rejection due to antiglomerular basement membrane glomerulonephritis (also known as Alport anti GBM Disease.) This is because the body recognises the ‘normal’ gene instead of the Alports gene and tries to reject the kidney. Only about 2% of kidney transplants are lost because of this, and genetic testing makes it possible to predict which patients are at an