Diagnosis, classification, basis of treatment of hyperphenylalaninemias

Neonatal mass screening is the common way to identify hyperphenylalaninemias (i.e. plasma Phe greater than or equal to 120 mu M similar to 2 mg/dl, Tyr less than or equal to 140 mu M similar to 2.5 mg/dl) due to Phenylalanine hydroxylase system deficiency. Once hyperphenylalaninemia (hyperPhe) has been detected, a complete diagnostic work-up must be applied to exclude defects in cofactor metabolism. While a tetrahydrobiopterin (BH4) defect is ruled out, the determination of plasma Phe concentration is the clue to differentiate the different degrees of enzyme deficiency: 1) Phe > 1000 mu M (16.5 mg/dl): classic PKU with mandatory Phe restricted diet; 2) Phe between > 600 mu M (similar to 10 mg/dl) e < 1000 mu M (16.5 mg/dl): 2) Phe type II with Phe restricted diet following the individual tolerance; 3) Phe steadily and on normal diet < 600 mu M (similar to 10 mg/dl): hyperPhe type III, without needing of treatment.The Phe restricted diet prevents mental retardation and neurological impairment. The goal of the treatment is to maintain plasma Phe levels between 120 and 360 mu M (similar to 2 and 6 mg/dl. In BH4 deficient patients dietary treatment, when needed, must be combined with pharmacological therapy to restore adequate levels of BH4 and specific neurotransmitters.This is thew first italian official report (one of the few worldwide published) on the topic.