Phenylketonuria

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

Epidemiology

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

Clinical presentation

Symptomatic patients demonstrate motor function impairment and mental retardation 1

Pathology

PKU is due to 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

Radiographic features

There are diffuse changes of the white matter due to dysmyelination, firstly in the periventricular/parieto-occipital white matter before affecting the subcortical white matter later 4.

MRI
  • T2: high signal in affected areas
  • DWI: reduced diffusion in acutely affected areas 4

Treatment and prognosis

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


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Inborn errors of metabolism

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