1. PHENYLKETONURIA
Stephanie Holton

2. Phenylketonuria Genotype:
Mutuation of the enzyme, phenylalanine hydroxylase (PAH)
Phenotype:
Mental Retardation, Seizures, Fair Skin, “Mousy Odor” & Eczema.

3. Phenylketonuria PAH Gene- Location: chromosome 12q22-24
Length: 79,278 bp’s (13 exons)
Over 450 mutations in the gene have been identified in patients with PKU.

4. 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.

5. Phenylketonuria

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

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

8. 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

9. 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)

10. References http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=261600