Department of Paediatrics, Child Neurology and Psychiatry, Sapienza Università di Roma , Rome , Italy.
Department of Neurology and Psychiatry, Sapienza Università di Roma , Rome , Italy.
Front Pediatr. 2014 Jun 23;2:57. doi: 10.3389/fped.2014.00057. eCollection 2014.
Phenylketonuria (PKU) is caused by the inherited defect of the phenylalanine hydroxylase enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). Neonatal screening programs and early treatment have radically changed the natural history of PKU. Nevertheless, an increased risk of neurocognitive and psychiatric problems in adulthood remains a challenging aspect of the disease. In order to assess the vulnerability of complex skills to Phe, we explored: (a) the effect of a rapid increase in blood Phe levels on event-related potentials (ERP) in PKU subjects during their second decade of life; (b) the association (if existing) between psychophysiological and neurocognitive features.
Seventeen early-treated PKU subjects, aged 10-20, underwent ERP [mismatch negativity, auditory P300, contingent negative variation (CNV), and Intensity Dependence of Auditory Evoked Potentials] recording before and 2 h after an oral loading of Phe. Neurocognitive functioning, historical and concurrent biochemical values of blood Phe, Tyr, and Phe/Tyr ratio, were all included in the statistical analysis.
Event-related potential components were normally detected in all the subjects. In subjects younger than 13 CNV amplitude, W2-CNV area, P3b latency, and reaction times in motor responses were negatively influenced by Phe-loading. Independently from the psychophysiological vulnerability, some neurocognitive skills were more impaired in younger patients. No correlation was found between biochemical alterations and neurocognitive and psychophysiological findings.
The vulnerability of the emerging neurocognitive functions to Phe suggests a strict metabolic control in adolescents affected by PKU and a neurodevelopmental approach in the study of neurocognitive outcome in PKU.
苯丙酮尿症（PKU）是由苯丙氨酸羟化酶遗传性缺陷引起的，该酶将苯丙氨酸（Phe）转化为酪氨酸（Tyr）。新生儿筛查计划和早期治疗极大地改变了 PKU 的自然病程。然而，成年后患神经认知和精神问题的风险增加仍然是该疾病具有挑战性的方面。为了评估复杂技能对 Phe 的易感性，我们探索了：（a）在生命的第二个十年中，快速增加血 Phe 水平对 PKU 受试者事件相关电位（ERP）的影响；（b）如果存在，心理生理和神经认知特征之间的关联。
17 名早期治疗的 PKU 受试者，年龄在 10-20 岁之间，在口服 Phe 负荷后 2 小时内进行 ERP [错配负波、听觉 P300、条件负变（CNV）和听觉诱发电位的强度依赖性]记录。神经认知功能、血 Phe、Tyr 和 Phe/Tyr 比值的历史和同期生化值均纳入统计分析。
所有受试者均正常检测到事件相关电位成分。在年龄小于 13 岁的受试者中，CNV 幅度、W2-CNV 面积、P3b 潜伏期和运动反应的反应时间受到 Phe 负荷的负面影响。独立于心理生理易感性，一些神经认知技能在年轻患者中受损更为严重。生化改变与神经认知和心理生理发现之间无相关性。
新兴神经认知功能对 Phe 的易感性表明 PKU 青少年需要严格的代谢控制，并且在 PKU 神经认知结果的研究中需要采用神经发育方法。
