Hyperphenylalaninaemia is the result of defects in the hepatic enzyme phenylalanine hydroxylase deficiency or the production of tetrahydrobiopterin1.

The goal for nutritional management is to maintain blood PHE concentrations within the desired range

PKU is classified by the dietary phenylalanine tolerance and pre-treatment blood concentrationsSeveral phenotypes in PKU are known, ranging from severe to milder forms. The need for dietary management and the amount of dietary PHE tolerated is an indication for the severity of the disorder, which is classified based on the severity of PKU at diagnosis3.

PKU is classified as severe or classical PKU by blood PHE concentrations >1200 µmol/l, with a dietary PHE tolerance up till 250 mg/day to maintain blood PHE levels <360 µmol/l.

PKU is classified as mild by PHE blood concentrations of 600-1200 µmol/l at diagnosis, with a dietary PHE tolerance <360 µmol/l.

Mild PKU is classified when blood PHE concentrations are maintained between 120-600 µmol/l on a normal diet.

Preliminary results of the ESPKU European guideline suggest that there is no strong evidence, but a general consensus that hyperphenylalaninaemia with blood Phe concentrations of < 360µmol/l should not be treated, but monitored at least during the first year of life due to possible late-onset PKU.

References

Blau N. Physicians’s guide to the diagnosis, treatment and follow up of Inherited Metabolic diseases 2014
Blau N, van Spronsen FJ, Levy HL. Lancet, 2010;376:1417-1427.
Donlon J, Levy H, Scriver CR Hyperphenylalaninemia: phenylalanine hydroxylase deficiency. In: Valle D, Beaudet AL, Vogelstein B et al. (eds) The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill, 2008, Ch. 77:pp. 1−14.

Hyperphenylalaninaemia - classification and goals