Despite numerous studies in human patients and animal models for phenylketonuria (PKU; OMIM#), the pathophysiology of PKU and the underlying causes of brain dysfunction and cognitive problems in PKU patients are not well understood. In this study, lumbar cerebral spinal fluid (CSF) was obtained immediately after blood sampling from early-treated adult PKU patients who had fasted overnight. Metabolite and amino acid concentrations in the CSF of PKU patients were compared with those of non-PKU controls. The CSF concentrations and CSF/plasma ratios for glucose and lactate were found to be below normal, similar to what has been reported for glucose transporter1 (GLUT1) deficiency patients who exhibit many of the same clinical symptoms as untreated PKU patients. CSF glucose and lactate levels were negatively correlated with CSF phenylalanine (Phe), while CSF glutamine and glutamate levels were positively correlated with CSF Phe levels. Plasma glucose levels were negatively correlated with plasma Phe concentrations in PKU subjects, which partly explains the reduced CSF glucose concentrations. Although brain glucose concentrations are unlikely to be low enough to impair brain glucose utilization, it is possible that the metabolism of Phe in the brain to produce phenyllactate, which can be transported across the blood-brain barrier to the blood, may consume glucose and/or lactate to generate the carbon backbone for glutamate. This glutamate is then converted to glutamine and carries the Phe-derived ammonia from the brain to the blood. While this mechanism remains to be tested, it may explain the correlations of CSF glutamine, glucose, and lactate concentrations with CSF Phe.

中文翻译：

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高苯丙氨酸血症会导致脑葡萄糖代谢低下吗？接受治疗的成人苯丙酮尿症患者的脑脊液检查结果

尽管对苯丙酮尿症（PKU；OMIM#）的人类患者和动物模型进行了大量研究，但 PKU 的病理生理学以及 PKU 患者脑功能障碍和认知问题的根本原因尚不清楚。在这项研究中，对禁食过夜的早期治疗的成年 PKU 患者进行血样采集后立即获取腰部脑脊液 (CSF)。将 PKU 患者脑脊液中的代谢物和氨基酸浓度与非 PKU 对照进行比较。发现脑脊液中葡萄糖和乳酸的浓度以及脑脊液/血浆比率低于正常水平，与葡萄糖转运蛋白 1 (GLUT1) 缺乏症患者的报告相似，这些患者表现出许多与未经治疗的 PKU 患者相同的临床症状。脑脊液葡萄糖和乳酸水平与脑脊液苯丙氨酸（Phe）呈负相关，而脑脊液谷氨酰胺和谷氨酸水平与脑脊液Phe水平呈正相关。 PKU 受试者的血浆葡萄糖水平与血浆 Phe 浓度呈负相关，这部分解释了脑脊液葡萄糖浓度降低的原因。尽管脑葡萄糖浓度不太可能低到足以损害脑葡萄糖利用，但脑中苯丙氨酸代谢产生苯乳酸（苯丙氨酸可以穿过血脑屏障输送到血液）可能会消耗葡萄糖和/或乳酸盐以生成谷氨酸的碳主链。然后，这种谷氨酸转化为谷氨酰胺，并将苯丙氨酸衍生的氨从大脑携带到血液中。虽然这一机制仍有待测试，但它可以解释脑脊液谷氨酰胺、葡萄糖和乳酸浓度与脑脊液 Phe 的相关性。