Blood-brain phenylalanine relationships in persons with phenylketonuria

被引:56
作者
Koch, R
Moats, R
Guttler, F
Guldberg, P
Nelson, M
机构
[1] Childrens Hosp Los Angeles, Dept Pediat & Radiol, Los Angeles, CA 90027 USA
[2] Univ So Calif, Sch Med, Los Angeles, CA USA
[3] Beckman Inst Technol, Pasadena, CA USA
[4] CALTECH, Dept Biol, Pasadena, CA 91125 USA
[5] Childrens Hosp Los Angeles, Div Neuroradiol, Los Angeles, CA 90027 USA
[6] John F Kennedy Inst, DK-2600 Glostrup, Denmark
关键词
phenylalanine; phenylketonuria; blood; brain; and transport;
D O I
10.1542/peds.106.5.1093
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Objectives. Clinicians caring for persons with phenylketonuria (PKU) have been perplexed by the occasional normal individual with the classical biochemical profile consistent with the diagnosis of PKU. Usually untreated subjects 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 levels, in comparison with elevated blood Phe levels, account for the occurrence of these occasional unaffected individuals with the biochemical profile consistent with PKU. Method. Magnetic resonance imaging/magnetic resonance spectroscopy was used to measure brain Phe content compared with simultaneously obtained blood Phe levels determined on the amino acid analyzer. This comparison was obtained 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. Similar measurements were obtained in 4 carriers of the gene causing PKU. Their blood levels varied between .068 and .109 mmol/L, with a mean of .091 mmol/L and simultaneously obtained brain levels of Phe varied between .06 and .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 brain 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 been treated but who have a biochemical profile consistent with classical PKU exhibit lower brain levels of Phe. Such individuals are exceptional and may not need the vigorous restriction of their blood Phe levels that is required by the majority of persons with PKU.
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收藏
页码:1093 / 1096
页数:4
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