Background
Hyperphenylalaninemia is broadly defined as the presence of blood phenylalanine levels that exceed the limits of the upper reference range (2 mg/dL or 120 µmol/L) without treatment but that are below the level found in patients with phenylketonuria (PKU). Phenylalanine levels that exceed 20 mg/dL (1200 µmol/L) are considered typical of classic PKU (see Phenylketonuria). In 2014, the American College of Medical Genetics and Genomics released a practice statement that recommended that PKU and hyperphenylalaninemia both be considered part of the spectrum of phenylalanine hydroxylase (PAH) deficiency.
Phenylalanine levels of 6 mg/dL (360 µmol/L) or less in patients consuming an unrestricted diet are generally considered to be a benign condition. No dietary phenylalanine restrictions are usually recommended in this instance. In contrast, dietary restriction is generally indicated among patients whose phenylalanine levels are more than 12 mg/dL (725 µmol/L); chronic phenylalanine levels in this range reportedly cause measurable intellectual impairment in children.
Practices of dietary treatment vary in children with phenylalanine levels in the intermediate range of 7-11 mg/dL (425-660 µmol/L). Most centers in the United States recommend restricting dietary phenylalanine when levels exceed 10 mg/dL (600 µmol/L). Some also recommend treatment for levels that exceed 8-9 mg/dL (480-545 µmol/L). The British Medical Research Council Working Party on PKU recommends dietary phenylalanine restriction when levels consistently exceed 6.6-10 mg/dL (400-600 µmol/L).