Hoeksma Marieke, Reijngoud Dirk-Jan, Pruim Jan, de Valk Harold W, Paans Anne M J, van Spronsen Francjan J
Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Section of Metabolic Diseases, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
Mol Genet Metab. 2009 Apr;96(4):177-82. doi: 10.1016/j.ymgme.2008.12.019. Epub 2009 Feb 6.
Left untreated, phenylketonuria biochemically results in high phenylalanine concentrations in blood and tissues, and clinically especially in severe mental retardation. Treatment consists of severe dietary restriction of phenylalanine with more or less normal intellectual outcome as result when started early enough. It is unclear whether treatment for life is necessary. A clear relationship between plasma phenylalanine concentrations and cerebral outcome exists, but the precise pathophysiological mechanism is not understood. In studies in mice with phenylketonuria, the cerebral protein synthesis rate is decreased when compared to controls. The aim of the present study was to determine the protein synthesis rate in relation to the plasma phenylalanine concentrations in-vivo in patients with phenylketonuria by positron emission tomography brain studies after an intravenous l-[1-(11)C]-tyrosine bolus. Results showed a significant negative relationship (R(2)=0.40, p<0.01) between plasma phenylalanine concentration and the cerebral protein synthesis rate in 19 patients with phenylketonuria. At increased plasma phenylalanine concentrations, i.e. above 600-800micromol/l, the cerebral protein synthesis rate is clearly decreased compared to lower phenylalanine concentrations. These data suggest that cerebral protein metabolism in untreated adults with phenylketonuria can be abnormal due to high plasma phenylalanine concentrations. Hence, we speculate that it is important to continue dietary treatment into adulthood, aiming at plasma phenylalanine concentrations <600-800micromol/l.
若不进行治疗，苯丙酮尿症在生化方面会导致血液和组织中苯丙氨酸浓度升高，在临床上尤其会导致严重智力发育迟缓。治疗方法包括严格限制苯丙氨酸的饮食摄入，若早期开始治疗，智力发育结果大致正常。尚不清楚是否需要终身治疗。血浆苯丙氨酸浓度与脑部发育结果之间存在明确关联，但具体的病理生理机制尚不清楚。在对苯丙酮尿症小鼠的研究中，与对照组相比，其大脑蛋白质合成速率降低。本研究的目的是通过静脉注射l-[1-(11)C]-酪氨酸推注后进行正电子发射断层扫描脑部研究，确定苯丙酮尿症患者体内蛋白质合成速率与血浆苯丙氨酸浓度之间的关系。结果显示，19例苯丙酮尿症患者的血浆苯丙氨酸浓度与大脑蛋白质合成速率之间存在显著负相关（R(2)=0.40，p<0.01）。当血浆苯丙氨酸浓度升高时，即高于600 - 800微摩尔/升，与较低的苯丙氨酸浓度相比，大脑蛋白质合成速率明显降低。这些数据表明，未治疗的成年苯丙酮尿症患者由于血浆苯丙氨酸浓度高，其大脑蛋白质代谢可能异常。因此，我们推测成年后继续饮食治疗很重要，目标是使血浆苯丙氨酸浓度<600 - 800微摩尔/升。
