Cognitive and behavioral impairment in mild hyperphenylalaninemia

Evinç S., Pektaş E., Foto-Özdemir D. , Yıldız Y. , Karaboncuk Y., Bilginer-Gürbüz B., ...More

TURKISH JOURNAL OF PEDIATRICS, vol.60, no.6, pp.617-624, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 6
  • Publication Date: 2018
  • Doi Number: 10.24953/turkjped.2018.06.001
  • Page Numbers: pp.617-624
  • Keywords: hyperphenylalaninemia, cognitive functions, intelligence quotient, EXECUTIVE FUNCTION, UNTREATED SUBJECTS, PREFRONTAL CORTEX, PHENYLKETONURIA, CHILDREN, PKU, PERFORMANCE


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 mu mol/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 mu mol/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 mu mol/L" and "Phe 240-360 mu mol/L" groups. Wechsler Intelligence Scale for Children-IV (WISC-IV), Conners' Continuous 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 that "all HPA" patients had significantly lower scores on all WISC-IV indexes compared to controls, except for Working Memory. Both "Phe 360-600 mu mol/L" and "Phe 240-360 mu mol/L" subgroups had lower Full Scale intelligence quotient (IQ) and Verbal Comprehension scores compared to controls. "All HPA" patients 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 mu mol/L are at higher risk for cognitive and attention-related problems, lowering the "safe" upper Phe level should be considered.