Transcript Alport Syndrome

Sara Kline
Period 6
3/25/10
ALPORT SYNDROME
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
 2nd 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 XChromosome “masks” the bad X-Chromosome but this
does not happen in men because they only have one XChromosome.
 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 XChromosome ONLY.
Bibliography
 http://www.bbc.co.uk/health/conditions/alport1.
shtml
 https://www.alportsyndrome.org/alportsub/alport_syndrome_genetics.html
 http://www.squidoo.com/alport_syndrome
 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?b
ook=gnd&part=alportsyndrome
 http://www.scielo.br/img/revistas/rboto/v71n6/e
n_a20fig04.gif
 http://ghr.nlm.nih.gov/condition=alportsyndrom
e