As elevated phenylalanine (Phe) is detrimental to brain functions, determininga safe upper limit of blood Phe is important for initiation of treatment plansand setting Phe targets in hyperphenlalaninemic patients. It is accepted thatPhe levels below 360 μmol/L does not impair brain function and hence doesnot require treatment. Therefore, we aimed to compare cognitive functions andattention-related problems among healthy children and untreated patients withhyperphenylalaninemia (HPA). This study included 41 hyperphenylalaninemicpatients (“all HPA group”) aged 6-16 years with untreated blood Phe between240 and 600 μmol/L and 29 healthy controls. “All HPA group” was furtherdivided into 2 subgroups according to their lifetime median blood Phe levels as“Phe 360-600 μmol/L” and “Phe 240-360 μmol/L” groups. Wechsler IntelligenceScale for Children–IV (WISC-IV), Conners’ Continuous Performance Test (CPT),Strength and Difficulties Questionnaire (SDQ) and Schedule for AffectiveDisorders and Schizophrenia for School-Age Children: Present and LifetimeVersion (K-SADS-PL) were performed as a comprehensive neurocognitive,attention and behavioral assessment. The study illustrated that “all HPA”patients had significantly lower scores on all WISC-IV indexes compared tocontrols, except for Working Memory. Both “Phe 360-600 μmol/L” and “Phe240-360 μmol/L” subgroups had lower Full Scale intelligence quotient (IQ) andVerbal Comprehension scores compared to controls. “All HPA” patients alsohad longer reaction times and more peer problems than controls, indicatingattention deficits and behavioral problems. Since the results demonstratedthat children with untreated Phe levels between 240-360 μmol/L are at higherrisk for cognitive and attention-related problems, lowering the “safe” upperPhe level should be considered.