Phenylketonuria (PKU)

Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine.

Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation and seizures. However, PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can be a very effective treatment. There is no cure. Damage done is irreversible so early detection is crucial.

Treatment

If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but only by eating a special diet low in phenylalanine for the rest of his or her life. This requires severely restricting or eliminating foods high in phenylalanine, such as meat, chicken, fish, nuts, cheese, legumes and other dairy products. Starchy foods such as potatoes, bread, pasta, and corn must be monitored. Infants may still be breastfed to provide all of the benefits of breastmilk, though the quantity must be monitored and supplementation will be required. Many diet foods and diet soft drinks that contain the sweetener aspartame must also be avoided, as aspartame consists of two amino acids: phenylalanine and aspartic acid.

Supplementary infant formulas are used in these patients to provide the amino acids and other necessary nutrients that would otherwise be lacking in a low phenylalanine diet. These can continue in other forms as the child grows up such as pills, formulas, and specially formulated foods. (Since phenylalanine is necessary for the synthesis of many proteins, it is required but levels must be strictly controlled). In addition, tyrosine, which is normally derived from phenylalanine, must be supplemented.)

The oral administration of tetrahydrobiopterin (a cofactor in the oxidation of phenylalanine) can reduce blood levels of the amino acid in certain patients.  The company BioMarin Pharmaceutical has produced a tablet preparation of the compound sapropterin (Kuvan),which is a form of tetrahydrobiopterin. Kuvan is the first drug that can help BH4-responsive PKU patients (defined among clinicians as 1/4 to 1/2 of the PKU population) keep their phenylalanine levels low PKU patients who respond to Kuvan (20-56% of those who try it) may also be able to increase the amount of protein they can safely eat.  After extensive clinical trials, Kuvan has been approved by the FDA for use in PKU therapy. Respected researchers and clinicials working with PKU are finding Kuvan a safe and effective addition to dietary treatment and beneficial in increasing quality of life for their patients.  Some concerns have been expressed over Kuvan's safety, cost, and the potential for PKU sufferers to override the benefits of the drug.

There are a number of other therapies currently under investigation, including gene therapy, and an injectable form of PAH. Previously, PKU-affected people were allowed to go off diet after approximately 8, then 18 years of age. However, most physicians now agree that this special diet should be followed throughout life.

More information can be found in the articles/websites listed below:

PKU Article.pdf

http://www.pku.com/