PHENYLKETONURIA

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PHENYLKETONURIA

• Stephanie Holton

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Phenylketonuria

• Genotype
• Mutuation of the enzyme, phenylalanine
  hydroxylase (PAH)
• Phenotype
• Mental Retardation, Seizures, Fair Skin, Mousy
  Odor Eczema.

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Phenylketonuria

• PAH Gene-
• Location chromosome 12q22-24
• Length 79,278 bps (13 exons)
• Over 450 mutations in the gene have been
  identified in patients with PKU.

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Phenylketonuria

• Normal PAH gene function-
• Responsible for the first step in processing the
  amino acid phenylalanine.
• Also, necessary for the conversion of
  phenylalanine to tyrosine.

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Phenylketonuria
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Phenylketonuria

• Conserved Domains-
• 1) ACT (35-109) regulatory role
• 2) euPHeOH (119-424)
• Catalyzes the first and rate-limiting step in the
  metabolism of phenylalanine
• Location of PAH mutation in PKU

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Phenylketonuria

• PAH Mutation-
• Most common is located at position 408
• A substitution of an Arginine with a
  Tryptophan(Arg408Trp).

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Phenylketonuria

• Aberrant Function-
• Reduces the activity of phenylalanine hydroxylase
  
• Phenylalanine ingested in foods cannot be
  metabolized and accumulates to toxic levels in
  the bloodstream and other tissues

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Phenylketonuria

• Aberrant Phenotype-
• The increased levels of Phenylalanine can cause
  brain damage, if left untreated.
• Tyrosine- necessary for production of certain
  neurotransmitters melanin (in hair in skin)

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References

• http//www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id
  261600
• http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?dbg
  enecmdRetrievedoptfull_reportlist_uids5053
• http//ghr.nlm.nih.gov/genepah