苯丙酮尿症（PKU）和轻度高苯丙氨酸血症（mHPA）患者的执行功能和代谢控制。

Executive functions & metabolic control in phenylketonuria (PKU) and mild hyperphenylalaninemia (mHPA).

机构信息

Center for Pediatric Research Leipzig, Department of Women and Child Health, Hospital for Children and Adolescents, University Hospital, Germany.

Center for Pediatric Research Leipzig, Department of Women and Child Health, Hospital for Children and Adolescents, University Hospital, Germany; Leipzig University Center for Rare Diseases, Philipp-Rosenthal-Str. 55, 04103 Leipzig, Germany.

出版信息

Mol Genet Metab. 2024 Sep-Oct;143(1-2):108544. doi: 10.1016/j.ymgme.2024.108544. Epub 2024 Jul 20.

DOI:10.1016/j.ymgme.2024.108544

PMID:39059271

Abstract

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).

CONCLUSION

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.

摘要

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）患者在智商测试和学业成绩方面基本正常。然而，代谢控制在不同发育阶段对更复杂认知能力（即执行功能[EF]）的影响仍不清楚。

方法

通过新生儿筛查识别并持续治疗的 28 名 PKU/mHPA 患者，年龄在 8-17 岁，对他们进行执行功能测试。分析当前（测试日和过去 10 个苯丙氨酸（Phe）值）和长期代谢控制（年龄期：儿童<6、6-10、青春期>10 岁、终生 Phe）与执行功能的关系。

结果

EF 值处于较低的正常范围（T 值的 IQR：47.35-51.00）。患者的反应时间明显慢于人群平均值（分散注意力/TAP：中位数 40，p<0.01）。长期和当前的代谢控制均与 EF 测试的表现相关：当前较高的 Phe 会损害反应时间（Go/No-Go，r=-0.387；工作记忆，r=-0.425；p<0.05）和计划能力（ToL，r=-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（TAP 遗漏率 r=-0.357 和-0.490，均 p<0.05）以及计划能力（ToL r=-0.422 和-0.387，青春期和终生，p<0.05）。