Abstract

Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism causing accumulation of phenylalanine resulting in cognitive, behavioural and pyramidal dysfunction. The prevalence of PKU is 1 per 10,000 live births in European countries. Treatment is lifelong adherence to a low phenylalanine diet.¹ Improvement outcomes after introducing dietary restrictions in adulthood or in the re–introduction after prolonged periods of non–compliance are largely limited to subjective changes in behaviour and well–being.² Few case reports address the changes in motor function.³ This case report provides further evidence for the beneficial effects of re–introducing a low phenylalanine diet in untreated adults.

A 41 year old medically retired nurse was admitted to hospital with functional decline. She had a background of PKU, which had been treated with a low phenyalanine diet from birth until 16 years old at which stage her diet was discontinued. At the age of 37 years she developed progressive visual loss to 6/60 bilaterally over a 6 month period. VEPs were delayed with small amplitude bilaterally. MRI of brain demonstrated extensive white matter changes. The patient then defaulted from follow up until her current admission 3 years later when she re–presented with a 6 month history of declining mobility, generalised apathy, behavioural disturbance, and further deterioration in her vision. On examination she was orientated but unable to follow 1 stage commands consistently. She required a hoist for transfer and was wheelchair dependant. Visual acuity was reduced to finger counting bilaterally and there was bilateral optic disc pallor. Limb examination demonstrated spasticity (Ashworth scale 3 bilaterally), sustained clonus, mild pyramidal weakness, hyperreflexia and extensor planters.

Initial investigations demonstrated a low folate (1.6 ug/L, normal range 3.1–17.5 ug/L). Her tyrosine was 56 umol/L with an elevated phenylalanine 1564 umol/L (120–480 umol/L), consistent with untreated PKU. She was given folate replacement and symptomatic treatment for spasticity. A low phenylalanine diet was commenced. Following normalisation of her phenylalanine (121 umol/L), there was an improvement in cognitive function, affect and behaviour. She was now able to complete an Addenbrooke's Cognitive Examination–revised (ACE–r) scoring 53/84 (she was unable to complete visual sections). Vision improved to 6/60 bilaterally. Her mild pyramidal weakness remained but her spasticity improved (Ashworth scale 1 bilaterally) and she was able to walk 40m with bilateral assistance.

This case highlights the importance of consideration dietary reinstitution as part of a rehabilitation regimen in untreated adults with PKU.