Neurological deterioration in adult phenylketonuria

J Inherit Metab Dis. 1989;12(4):451-7. doi: 10.1007/BF01802042.


A 28-year-old man with classical phenylketonuria had increased seizure frequency and rapidly progressive spasticity. There was a marked reduction of biogenic amine neurotransmitter metabolites in cerebrospinal fluid. Dietary therapy reduced serum phenylalanine levels, improved symptoms of hypertonicity, and cerebrospinal fluid neurotransmitter metabolites became normal. An adolescent male with classical phenylketonuria, treated by dietary restriction until age 6 years, was assessed for decreasing school performance at 18 years. Cerebrospinal fluid biogenic amine neurotransmitter metabolites were significantly reduced. Magnetic resonance imaging in both subjects showed multiple areas of increased signal intensity in cerebral white matter. Neuropathological changes in classical phenylketonuria have been characterized as a dysmyelinating or demyelinating process. Neurochemical studies show a defect in brain lipids and biogenic amine metabolism. In the past, dietary therapy was directed at reducing hyperphenylalaninaemia only during the first decade of life. This report, as well as other studies, indicates that dietary therapy should be lifelong in patients with classical phenylketonuria, in order to prevent progressive and insidious neurological deterioration in later life.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Biogenic Amines / cerebrospinal fluid
  • Biogenic Amines / metabolism
  • Biopterin / analogs & derivatives
  • Biopterin / metabolism
  • Brain / pathology*
  • Diet Therapy
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Muscle Spasticity / complications
  • Neopterin
  • Phenylalanine / blood
  • Phenylalanine / therapeutic use
  • Phenylketonurias / drug therapy
  • Phenylketonurias / metabolism
  • Phenylketonurias / pathology*
  • Seizures / etiology*


  • Biogenic Amines
  • Biopterin
  • Phenylalanine
  • Neopterin