背景:由于新生儿筛查和早期治疗,苯丙酮尿症(PKU)和轻度高苯丙氨酸血症(mHPA)的患者基本正常,在智商测试和学术成就方面。然而,代谢控制在不同发育阶段对更复杂的认知能力的影响,即执行功能(EF),还不清楚。
方法:对28例PKU/mHPA患者进行EF检测,8-17岁,通过新生儿筛查确定并持续治疗。与当前(测试日和过去10个苯丙氨酸(Phe)值)和长期代谢控制(年龄:儿童期<6,6-10,青春期>10年,一生Phe)进行了分析。
结果:EF处于较低的规范范围(T值的IQR:47.35-51.00)。患者反应时间明显慢于人群平均值(注意力分散/TAP:中位数40,p<0.01)。两者,长期和当前的代谢控制与EF测试中的表现相关:较高的当前Phe受损反应时间(Go/No-Go,r=-0.387;工作记忆,r=-0.425;p<0.05)和计划能力表现(ToLr=-0.465,p<0.01)。儿童期和青春期较高的长期Phe值主要影响注意力(分别为-0.357和-0.490,p<0.05)以及计划能力(ToLr=-0.422和-0.387,青春期和终生,p<0.05)。
结论:PKU/mHPA的当前和长期代谢控制,包括青春期,影响EF,特别是影响反应时间和计划能力。在患者咨询中应该考虑到这一点。
BACKGROUND: Due to newborn screening and early treatment, patients with
phenylketonuria (PKU) and mild hyperphenylalaninemia (mHPA) develop largely normal, in terms of IQ testing and academic attainment. However, the impact of metabolic control in various stages of development on more complex cognitive abilities, i.e. executive functions (EF), is still unclear.
METHODS: EFs were tested in 28 patients with PKU/mHPA, aged 8-17 years, identified by newborn screening and continuously treated. The relation to current (testing day & past 10 phenylalanine (Phe) values) and long-term metabolic control (age periods: childhood <6, 6-10, adolescence >10 years, lifetime Phe) was analyzed.
RESULTS: EFs were in the lower normative range (IQR of T-values: 47.35-51.00). Patients reaction time was significantly slower than the population mean (divided attention/TAP: median 40, p < 0.01). Both, long-term and current metabolic control correlated with performance in EF tests: Higher current Phe impaired reaction times (Go/No-Go, r = -0.387; working memory, r = -0.425; p < 0.05) and performance in planning ability (ToL r = -0.465, p < 0.01). Higher long-term Phe values both in childhood and adolescence mainly affected attention (omissions/TAP r = -0.357 and - 0.490, respectively, both p < 0.05) as well as planning ability (ToL r = -0.422 and - 0.387, adolescence and lifetime, p < 0.05).
CONCLUSIONS: Current and long-term metabolic control in PKU/mHPA, including the adolescent period, influence EFs, especially affecting reaction time and planning abilities. This should be taken into account in patient counselling.