Last revised by Jeremy Jones on 18 Sep 2021

Phenylketonuria (PKU) is an inborn error of metabolism resulting from abnormal metabolism of phenylalanine. If untreated, patients can develop central nervous system impairment. 

PKU is inherited as an autosomal recessive disorder with an incidence of 1 in 10,000. It is more common in Caucasians 1,5

Children with phenylketonuria are generally healthy at birth and develop normally in the early course of the disease. However, if not treated they eventually develop 6:

Phenylketonuria is inherited in an autosomal recessive pattern and is due to a mutation in the PAH gene 6. The mutation results in a deficiency of the hepatic enzyme phenylalanine hydroxylase which converts the amino acid phenylalanine, a large neutral amino acid to tyrosine. The resultant accumulation phenylalanine in the blood competes for transport across the blood-brain barrier with other amino acids via the large neutral amino acid transporter. As a result, the availability of other large neutral amino acids in neurons is decreased to the brain resulting in impaired neurotransmitter and protein synthesis 2.

  • T2/FLAIR:
    • high signal in affected areas
    • occurring firstly in the periventricular/parieto-occipital white matter before eventually affecting the subcortical white matter (due to hypomyelination and edema 6)
    • atrophy and compensatory ventricular dilatation may occur eventually
  • DWI: reduced diffusion in acutely affected areas 4
  • MR spectroscopy: phenylalanine peak at 7.37 ppm 6

Treatment is with a phenylalanine-restricted diet 3 with the avoidance/restriction of foods such as breast milk, meat, nuts, dairy products and starchy foods (e.g. potatoes, bread) 5. Traditionally this has been enforced only during childhood, but recent evidence suggests lifelong dietary restriction is probably worthwhile 5. Reversal of neuroimaging changes are possible after adherence to a phenylalanine-restricted diet 6

Removing phenylalanine from the diet can increase the risk of developing selenium deficiency since many foods containing this amino acid also are the main sources of dietary selenium.

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Cases and figures

  • Case 1
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