Blood-brain phenylalanine relationships in persons with phenylketonuria

Objectives. Clinicians caring for persons with phenylketonuria (PKU) have b een perplexed by the occasional normal individual with the classical bioche mical profile consistent with the diagnosis of PKU. Usually untreated subje cts with the biochemical profile of blood phenylalanine (Phe) levels >1200 mu mol/L are severely mentally retarded and may have neurological findings. preliminary reports have recently appeared suggesting that low brain Phe l evels, in comparison with elevated blood Phe levels, account for the occurr ence of these occasional unaffected individuals with the biochemical profil e consistent with PKU. Method. Magnetic resonance imaging/magnetic resonance spectroscopy was used to measure brain Phe content compared with simultaneously obtained blood P he levels determined on the amino acid analyzer. This comparison was obtain ed in 5 normal non-PKU persons, 4 carriers of the gene causing PKU, and in 29 individuals with the proven form of the disorder. Results. Blood-brain measurements in 5 normal persons ranged from .051 to . 081 mmol/L, with a mean of .058 mmol/L. Their simultaneously measured brain levels of Phe ranged from .002 to .15 mmol/L, with a mean of .09 mmol/L. S imilar measurements were obtained in 4 carriers of the gene causing PKU. Th eir blood levels varied between .068 and .109 mmol/L, with a mean of .091 m mol/L and simultaneously obtained brain levels of Phe varied between .06 an d .21 mmol/L, with a mean of .11 mmol/L. Twenty subjects with a mean IQ of 104 exhibited a mean blood level of 1.428 mmol/L and a simultaneous mean br ain level of .23 mmol/L, whereas 9 persons with a mean IQ of 98.7 exhibited a mean blood Phe level of 1.424 and a mean brain Phe level of .64 mmol/L. The correlation between blood and brain levels was not significant. Conclusion. In usual cases, intellectually normal persons who have never be en treated but who have a biochemical profile consistent with classical PKU exhibit lower brain levels of Phe. Such individuals are exceptional and ma y not need the vigorous restriction of their blood Phe levels that is requi red by the majority of persons with PKU.