tified PKU conditions that range from a mild to severe defect in the PAH enzyme. Classical PKU, where there is close to total absence in activity of the PAH enzyme accounts for approximately 60 percent of all PKU cases and is the most severe. The PAH location or locus is on the tip of the long arm of chromosome 12. Its map location is 12q22-24.1 and it is considered to be a large gene being 90 kb long with 13 exons and encoding a polypeptide of 452 amino acids.(Scriver,144) Genetically, PKU is not always caused by a single gene defect because there are two other enzymes produced by different genes that can effect the efficiency of PAH. However, mutation within the PAH gene is the main determinant of PKU.(Guldburg,71) There are over 365 identified possible mutant alleles that play a role in PKU and 105 of the mutations are found on the gene encoding for PAH. Fortunately, two-thirds of all mutant alleles are confined within four haplotypes. Most PAH variants are single-base substitutions such as missense, nonsense and splicing mutations. Common examples of these single-base substitutions would be a splicing mutation in intron 12, missense mutations in exons 7,9 and 12 or a deletion in the region of exons 1 and 2. (Clarke, 47)Throughout the world,” PKU is one of the most common defects of amino acid metabolism and is also one of the most common metabolic, inherited disorders effecting brain development.”(p346,Mange) PKU affects about 1 in 10,000-15,000 newborns in the United States and Europe and about 1 in 16,500 in China. There are also particular groups that are more frequently affected, 1 in 2,600 among Turks and 1 in 4,000 among the Irish. Similarly, groups with a rare frequency are the Ashkenazi Jews, Finns, African Americans and Japanese. In Caucasians the carrier frequency of PKU averages to 1 in 50 males and females which indicates no discrimination between genders. It is not yet certain why there are diff...
