Phenylketonuria is an autosomic recessive disorder and is an orpan disease.

Phenylketonuria was first described in 1934 by the Norwegian Dr. Asbjørn Følling, but it was not until 20 years later, in 1954, that Professor Horst Bickel suggested the use of a diet low in phenylalanine.

It was only in 1962 that Dr. Robert Guthrie devised a screening test for it.

Phenylketonuria is a hereditary disease of the metabolism, characterised by a deficiency in the enzyme phenylalanine hydroxylase (PAH).

PAH is an enzyme needed to convert phenylalanine (PHE) into tyrosine (TYR), and this conversion helps keep the body in good health (body structure etc.).

«In the absence of PAH, PHE accumulates in the human body and causes disease.»

Phenylalanine is an amino acid (AA). Several AAs combine to make a protein. There are 20 AAs, of which 8 are known as &lquot;essential&rquot; amino acids. These cannot be synthesized by the body. As it cannot produce them, they must be provided in the diet. PHE is consumed by millions of people every day; for instance, it is found (as one of the main constituents) in aspartame (an ingredient used as a sugar substitute in some &lquot;light&rquot; products).

If there is not enough PAH or none at all, plasma levels of phenylalanine (serum phenylalanine) are increased , resulting in the disruption of the proper functioning of the body (in 2% of cases, the problem stems from the cofactor of PAH).

The increase in serum phenylalanine causes poisoning and symptoms which are characterised by serious neurological disorders together with disorders of the skin appendages (body hair, hair on the head, etc) and generally a low level of pigmentation.

Phenylketonuria is defined as a phenylalanine level > 20 mg/dL (1200 µmol/L)

« What about me, with my 10 mg, do I have phenylketonuria or not? »

Classification

It is classified according to the residual activity of the enzyme and the level of phenylalanine in the blood :

• Typical or classic PKU (activity 20 mg/dL (1200 µmol/L)
• Atypical or moderate PKU (activity 1-5 %), level between 10 mg/dL (600 µmol/L) and 20 mg/dL
• Elevated phenylalanine (activity >5 %), level < 10 mg/dL: it is essential to inform the family (to monitor and thus protect future generations) but a strict diet is not introduced.

Frequency of phenylketonuria

Phenylketonuria is an autosomal recessive disorder and is an orphan disease. In France, one child in 17 000 is born with this disease (NIH, 2006). In Europe, the rate ranges from 1/4000 to 1/40 000. It seems to be much more common among Americans, with a prevalence between one child in 10 000 and one in 15 000.