Accertamento diagnostico, nosografia, principi di trattamento delle iperfenilalaninemie

Neonatal mass screening is the common way to identify hyperphenylalaninemias (i.e. plasma Phe ≥ 120 μM ∼2 mg/ dl, Tyr ≤ 140 μM ∼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 μM (16.5 mg/dl): classic PKU with mandatory Phe restricted diet; 2) Phe between > 600 μM (∼10 mg/dl) e <1000 μM (16.5 mg/dl): hyperPhe type II with Phe restricted diet following the individual tolerance; 3) Phe steadily and on normal diet <600 μM (∼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 μM (∼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.