Sara Kline Period 6 3/25/10

What is Alport Syndrome?  Chromosomal disorder that damages tiny blood vessels in the kidneys - - these tiny blood vessels are called glomeruli.  The disorder decreases the effectiveness of the kidney’s filtering system which causes build up of fluids and waste in the body.  The disorder is mild in women and for men the symptoms are more severe and get worse faster.

History  The syndrome was named for Dr. Alport (1927) who noted that a British family who developed renal disease and deafness were mainly men who ended up dying as a result of kidney problems. He also noted that the females were less affected and lived longer.

Symptoms of the Disorder  Abnormal urine color  Ankle, feel, leg, around the eye swelling (swelling in general on the body)  Blood in urine  Decrease or loss in vision (loss is most common in males)  Sometimes there are no symptoms

Facts about the Disorder  2 nd most common inherited cause of Kidney failure  Occurs when a special type of collagen found in the Kidney is missing or abnormal  1 in 5,000 children are affected  More common in males due to inheritance  Difficult to detect (except genetic testing in certain families)  The disorder does not affect the phenotype of a person. You cannot tell from the looks of someone whether or not they have the disease with the exception of some swelling.

Treatment for the Disorder  No real treatment  To reduce the severity and rapidity one can have restrictions on salt, protein and phosphate in their diet.  Eventually some people with the disorder may need dialysis and/or a kidney transplant **Stem cell research on a model mouse found that stem cells were able to regenerate damaged cells affected by Alport Syndrome (this could mean some type of better treatment in the future)

The Genetics of Alport Syndrome  Caused by defects in the chains of type 4- Collagen  Type 4-Collagen is a family of 6 different proteins: alpha-1 through alpha-6  Mutations in alpha-3, alpha-4 and alpha-5 chains cause Alport Syndrome

3 Different Types 1. XLAS 2. ARAS 3. ADAS

XLAS  X-linked  Most common form of the disorder  Type 4 Alpha-5 Collagen Mutations  Accounts for 80-85% of cases  When the mother is the carrier, the chance of her children getting the disorder is 50% because she has to X chromosomes (which is where the disorder is carried). She has 1 X-chromosome affected, and 1 X-chromosome unaffected.

XLAS (Continued)  Males who carry the mutation will pass on the disease to their daughter because they only have one X-chromosome which is affected by the disorder. They will not pass it to their sons because they give their sons their Y-chromosome which does not carry the disorder.  Daughters who inherit will be carriers because the good X- Chromosome “masks” the bad X-Chromosome but this does not happen in men because they only have one X- Chromosome.  Daughters can inherit the disease from their mom or dad and boys can only inherit the disease from their mothers.  10% of children have spontaneous mutation and neither parent carries a mutation.

XLAS Diagram

ARAS inheritance  Autosomal recessive  10-15% of cases  Mutations in alpha-3 or alpha-4 Collagen  Happens when both copies of a gene are defective  When each parent carries a mutation in Collagen Alpha-3 or 4 there is a 25% probability that with every pregnancy the child could have the ARAS form of Alport Syndrome

ADAS Inheritance  Autosomal Dominant  Rare form  5% of cases  Mutations in EITHER alpha-3 or alpha-4 in each cell. Each child of affected parent has 50% chance of inheriting the mutation.

Dominant or Recessive? Gene or Chromosomal?  Alport Syndrome can be Dominant (ADAS) or Recessive (ARAS) due to the different kinds of inheritance  The disorder is a genetic AND chromosomal disorder.  Genetic forms are ARAS and ADAS (mentioned above)  Chromosomal form is XLAS through the X- Chromosome ONLY.

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