Phenylketonuria, or PKU, is a metabolic genetic disease that leads to the surplus of phenylalanine (Phe) amino acid in the body. This anomaly appears due to the defective phenylalanine hydroxylase (PAH) gene encoding the enzyme which converts phenylalanine to tyrosine (Tyr). Phenylalanine is an essential amino acid for the protein synthesis, so it cannot be produced by body itself but it must be introduced through daily diet in the adequate amount to guarantee growth and repair of body tissues.

In subjects affected by PKU the conversion failure causes an accumulation of phenylalanine in blood and in the brain, which affects the normal operations of the main brain messengers, including dopamine and serotonin, causing mental disability, neurological and behavioral disorders.

PKU can be easily diagnosed through neonatal screening between 48 and 72 hours after birth. It has been mandatory by law n°104/1992 and it has been expanded to other 40 pathologies by law 167/2016. In case of families-at-risk and when the possible mutations can be predicted, it is possible to make a prenatal diagnosis by genetic analysis.


Phenylketonuria is an autosomal recessive genetic disease, which occurs when both genes for PAH are “defective”. The position and nature of the mutation in the genes determine the effects on the activity of the PAH enzyme and consequently the severity of the pathology, that is classified as mild, moderate or classic/severe, based on the values in the Phe blood reached on a free diet. Another variant is due to the gene mutation for the synthesis or regeneration of the enzymatic cofactor tetrahydrobiopterin (BH4).

Approximately 1 out of 50 people has a defective PKU gene, meaning that he is a still immune carrier. There is a little chance that two carriers will encounter each other – only about 1 out of 2500, and for this reason PKU is defined as a rare disease: in Europe the annual number of children born with PKU is 1/10.000 born alive.

Dietetic treatment

Waiting for future treatments like enzyme replacement therapy or gene therapy, the dietetic treatment is the only actually therapy for the management of PKU. To avoid damage, the dietetic restriction must start from the first month of life, guaranteeing an adequate intake of energy and protein based on age and a controlled amount of phenylalanine.

The dietetic treatment consists in:

  • - Consumption of fruit, vegetables and limited number of foods;
  • - Use of low-protein substitutes of common foods to cover energy needs (Taranis / Harifen products);
  • - Use of amino acid mixtures to cover individual protein needs (Numefen / Antifen line);
  • - Restriction of foods naturally containing proteins such as meat, eggs, legumes, milk, cheese, pasta, bread and derivatives, carbonated drinks containing aspartame;

Although long-term studies are needed to evaluate efficacy and safety, an alternative to the traditional dietary treatment is the use of mixtures with “Large neutral amino acids” (LNAAs) (Antifen Arancia, Antifen R) that compete with the phenylalanine at the level of the LAT1 transporter in the blood-brain barrier. This alternative ensures a less rigid diet combined with a reduction in Phe values in the brain. Further alternatives can be the use of prolonged absorption amino acids mixture and glycomacropepetide (GMP).