Abstract

Phenylketonuria (PKU) is a relatively common autosomal recessive disorder. The frequency of PKU among Caucasians populations is approximately 1:10.000. PKU is primarily a consequence of a deficiency in phenylalanine hydroxylase (PAH) activity, and un-treated PKU patients develop severe mental retardation. The absence of this enzymatic activity causes disturbances in tyrosine and tryptophan metabolism and diminished formation of catecholamine (dopamine), melanin and serotonin. In the present study, nucleotide sequence mutations were examined and detected in Egyptian phenylketonuria (PKU) patients. Total genomic DNA was extracted from the blood of six PKU patients and specific PAH primers were used to amplify genomic DNA fragments. Nucleotide sequences were processed using Human Splicing Finder software to remove introns and predict cDNAs. Processed cDNA sequences were aligned with reference sequence in the GenBank and healthy control for detection of mutations. The results indicated different sequence polymorphism, which can cause mild or severe mutations. The severity of sequence mutation was correlated with the accumulation of phenylalanine amino acid in the blood. This study is an attempt to early detection of PAH mutations, to control phenylketonuria genetic disorder in Egyptian population.

Key words: Phenylketonuria (PKU), phenylalanine hydroxylase (PAH), Phenylalanine.