Cognitive and behavioral impairment in mild hyperphenylalaninemia.

Evinç SG, Pektaş E, Foto-Özdemir D, Yıldız Y, Karaboncuk Y, Bilginer-Gürbüz B, Dursun A, Tokatlı A, Coskun T, Öktem F, Sivri HS. Cognitive and behavioral impairment in mild hyperphenylalaninemia. Turk J Pediatr 2018; 60: 617-624. As elevated phenylalanine (Phe) is detrimental to brain functions, determining a safe upper limit of blood Phe is important for initiation of treatment plans and setting Phe targets in hyperphenlalaninemic patients. It is accepted that Phe levels below 360 μmol/L does not impair brain function and hence does not require treatment. Therefore, we aimed to compare cognitive functions and attention-related problems among healthy children and untreated patients with hyperphenylalaninemia (HPA). This study included 41 hyperphenylalaninemic patients (all HPA group) aged 6-16 years with untreated blood Phe between 240 and 600 μmol/L and 29 healthy controls. All HPA group was further divided 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 Intelligence Scale for Children-IV (WISC-IV), ConnersContinuous Performance Test (CPT), Strength and Difficulties Questionnaire (SDQ) and Schedule for Affective Disorders and Schizophrenia for School-Age Children: Present and Lifetime Version (K-SADS-PL) were performed as a comprehensive neurocognitive, attention and behavioral assessment. The study illustrated thatall HPApatients had significantly lower scores on all WISC-IV indexes compared to controls, except for Working Memory. BothPhe 360-600 μmol/LandPhe 240-360 μmol/Lsubgroups had lower Full Scale intelligence quotient (IQ) and Verbal Comprehension scores compared to controls.All HPApatients also had longer reaction times and more peer problems than controls, indicating attention deficits and behavioral problems. Since the results demonstrated that children with untreated Phe levels between 240-360 μmol/L are at higher risk for cognitive and attention-related problems, lowering thesafe` upper Phe level should be considered.