PHENYLKETONURIA Stephanie Holton Phenylketonuria Genotype Mutuation of the

PHENYLKETONURIA Stephanie Holton

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

Phenylketonuria PAH Gene • Location: chromosome 12 q 22 -24 • Length: 79, 278 bp’s (13 exons) • Over 450 mutations in the gene have been identified in patients with PKU.

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.

Phenylketonuria

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

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

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

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)

References http: //www. ncbi. nlm. nih. gov/entrez/dispomim. cg i? id=261600 http: //www. ncbi. nlm. nih. gov/entrez/query. fcgi? d b=gene&cmd=Retrieve&dopt=full_report&list _uids=5053 http: //ghr. nlm. nih. gov/gene=pah