Phenylketonuria is an autosomal recessive disease caused by mutations in the gene coding for phenylalanine hydroxylase (chromosome 12q). Phenylalanine hydroxylase deficiency produces elevated phenylalanine concentrations in plasma, CSF, and urine as a direct result of the inability to convert phenylalanine to tyrosine. Mutations in the gene for PAH result in either failure to produce a PAH enzyme or production of an enzyme with decreased catalytic activity. This leads to an elevation of the blood phenylalanine (phe) level and to increased transport of phe into the brain. Phe itself is thought to be a direct cause of neurotoxicity in PKU. Neurotransmitter deficiency and decreased protein synthesis in the brain may be other mechanisms of neurotoxicity. Inhibition of the enzyme tyrosinase by elevated phe levels leads to decreased melanin synthesis in an untreated patient, resulting in hypo-pigmentation.
People with PKU need to follow a diet that limits foods with phenylalanine. The diet should be followed carefully and be started as soon after birth as possible. Food mainly suggested are Milk and cheese, Eggs, Nuts, Soybeans, Beans, Chicken, beef, or pork, Fish, Peas, Beer. The U.S. Food and Drug Administration (FDA) have approved the drug sapropterin dihydrochloride (Kuvan®) for the treatment of PKU. These treatments include large neutral amino acid supplementation, which may help prevent phenylalanine from entering the brain, and enzyme replacement therapy, which uses a substance similar to the enzyme that usually breaks down phenylalanine.
Projects like ‘The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness’ in progress. Treatments and drugs By Mayo Clinic Staff.
Pathogenic mutations were identified in 99% of the alleles screened, with the two most common mutations (p.R408W and IVS12+1G>A) accounting for 30.7% of alleles. Their birth prevalence is: PKU 1/30,000. Congenital/genetic disorders was 24.7 %; and among children under 5, 21. 8 %.