Alport Syndrome

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Alport Syndrome

• Sara Kline
• Period 6
• 3/25/10

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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
  kidneys 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.

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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.

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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

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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.

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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)

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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

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3 Different Types

1. XLAS
2. ARAS
3. ADAS

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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.

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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.

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XLAS Diagram
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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

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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.

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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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Bibliography

• http//www.bbc.co.uk/health/conditions/alport1.sht
  ml
• https//www.alportsyndrome.org/alport-sub/alport_s
  yndrome_genetics.html
• http//www.squidoo.com/alport_syndrome
• http//www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book
  gndpartalportsyndrome
• http//www.scielo.br/img/revistas/rboto/v71n6/en_a
  20fig04.gif
• http//ghr.nlm.nih.gov/conditionalportsyndrome