Although approximately 1–2% of cases of hyperphenylalaninemia are based on mutations in genes coding for enzymes involved in BH4 biosynthesis or regeneration [24, 25], some patients with defects in BH4 biosynthesis (such as Segawa disease and sepiapterin reductase deficiency) present without hyperphenylalaninemia [26, 27]. This evidence concerns the gene SPR and Hyperphenylalaninemia.