What is phenylketonuria?

Phenylketonuria is a disease caused by a deficiency of the enzyme called phenylalanine hydroxylase. This enzyme, normally made by the liver, has the function of transforming an amino acid found in proteins, phenylalanine. Thus, the phenylalanine hydroxylase enzyme being absent or insufficient, phenylalanine is not transformed into tyrosine and accumulates in the body, particularly in the brain. This accumulation of phenylalanine is toxic to nerve cells.

Although it is the most common metabolic disease, phenylketonuria is a very rare disease. In North America, the prevalence of this disease is 1 in 12,000 cases. Despite its low occurrence, phenylketonuria still presents variants.

The most common type is a deficiency of the enzyme phenylalanine hydroxylase. When there is a complete absence of this enzyme, it is called a classic PCU, its most severe form. When there is an enzymatic activity of 3%, it is an atypical PCU; an activity of 3 to 6% is a moderate form of PCU. This means that in the latter two cases the phenylalanine hydroxylase enzyme is not completely absent and transforms a small amount of the amino acid phenylalanine.

There is also another type of PCU where the enzyme phenylalanine hydroxylase is not involved. It is rather a deficiency of the cofactor, tetrahydrobiopterin (BH4), a molecule that helps the enzyme transform phenylalanine.

How is Phenylketonuria treated?

A diet low in phenylalanine must be introduced as soon as the diagnosis is posed in order to maintain the phenylalanine level below the toxic threshold. Since phenylalanine is a protein component, any food containing too much protein is banned: meat, dairy, fish, eggs, and cereals. Fruits and vegetables also contain proteins, but in varying amounts; they must therefore be weighed and counted. Only sugars and oils can be consumed freely. Other essential amino acids found in proteins are provided by dietary supplements.

Such a diet is essential for the normal growth of the child. From birth to adolescence, the brain is in full development, and a high rate of phenylalanine irremediably compromises this development by causing the death of nerve cells, resulting in severe mental retardation. In adolescence and adulthood, the diet should be continued because, although this effect is reversible, a high level of phenylalanine can cause a decrease in neurotransmitters.

Source: AQMMR, 2014.