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Phenylketonuria (PKU)

Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH).1,2



Overview of PKU

Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by a deficiency of the enzyme phenylalanine hydroxylase (PAH), which is required to metabolise phenylalanine (Phe), an amino acid found in all protein-containing foods.1,2 In case of PAH deficiency results in abnormally high levels of Phe in the blood, and toxic concentrations in the brain, leading to brain damage and affecting cognitive, behavioural and emotional function.2,3

PKU is an autosomal recessive disease, therefore if both parents are PKU gene carriers, their baby has a 1 in 4 chance of having the disease.1,4

Sustained high Phe levels cause neurological and neuropsychological complications:2,3

  • Mood disturbances
  • Tremors
  • Cognitive problems
  • Executive function deficits

Symptoms of PKU:

  • Children may have reduced IQ, memory problems, loss of attention and impulse control, as well as social difficulties and decreased self-esteem.3
  • The IQ of adults with PKU is lower than the general population, with impairments in executive function, such as attention, cognitive flexibility and inhibitory control, depression, anxiety and stress.5-7
  • Higher prevalence of physical comorbidities than the general population, including obesity, renal insufficiency, hypertension and osteoporosis.8


  1. van Spronsen FJ et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017;5(9):743-56.
  2. Blau N et al. Phenylketonuria. Lancet 2010;376(9750):1417-27.
  3. Enns GM et al. Suboptimal outcomes in patients with PKU treated early with diet alone: revisiting the evidence. Mol Genet Metab 2010;101:99-109.
  4. NORD. Phenylketonuria. Available at: https://rarediseases.org/rare-diseases/phenylketonuria/. Accessed March 2023.
  5. Bilder DA et al. Systematic review and meta-analysis of neuropsychiatric symptoms and executive functioning in adults with phenylketonuria. Dev Neuropsychol 2016;41(4):245-60.
  6. Jahja R et al. Cognitive profile and mental health in adult phenylketonuria: A PKU-COBESO study. Neuropsychology 2017;31(4):437-47.
  7. Clacy A et al. Depression, anxiety, and stress in young adults with phenylketonuria: Associations with biochemistry. J Dev Behav Pediatr 2014;35(6):388-91.
  8. Burton B et al. Prevalence of comorbid conditions among adult patients diagnosed with phenylketonuria. Mol Genet Metab 2018;125(3): 228-34.