Jahja Rianne, Huijbregts Stephan C J, de Sonneville Leo M J, van der Meere Jaap J, Legemaat Amanda M, Bosch Annet M, Hollak Carla E M, Rubio-Gozalbo M Estela, Brouwers Martijn C G J, Hofstede Floris C, de Vries Maaike C, Janssen Mirian C H, van der Ploeg Ans T, Langendonk Janneke G, van Spronsen Francjan J
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen.
Department of Clinical Child and Adolescent Studies, Leiden University.
Neuropsychology. 2017 May;31(4):437-447. doi: 10.1037/neu0000358. Epub 2017 Mar 20.
Despite early dietary treatment phenylketonuria patients have lower IQ and poorer executive functions compared to healthy controls. Cognitive problems in phenylketonuria have often been associated with phenylalanine levels. The present study examined the cognitive profile and mental health in adult phenylketonuria, in relation to phenylalanine levels and tetrahydrobiopterin treatment.
Fifty-seven early treated adult patients with phenylketonuria and 57 healthy matched controls (18-40 years) performed IQ subtests and executive function tests from the Amsterdam Neuropsychological Tasks. They also completed the Adult Self-Report on mental health problems. Analyses of variance were performed to examine group differences.
Patients with phenylketonuria had normal IQs although lower than controls. They performed poorer on working memory, inhibitory control, and sustained attention tasks. Patients reported Depressive and Avoidant Personality problems more frequently. Specifically, patients with childhood and lifetime phenylalanine ≥360 μmol/L had poorer cognitive and mental health outcomes than controls. In a subset of patients, comparisons between patients on and off tetrahydrobiopterin showed that nontetrahydrobiopterin users (matched for childhood, pretreatment phenylalanine) were slower (on number of tasks) and reported more mental health problems.
Adult patients had lower IQ and poorer executive functions than controls, resembling problems observed in younger patients with phenylketonuria, as well as more internalizing problems. Group differences and phenylalanine-outcome associations were smaller than those observed in younger populations. A subset of nontetrahydrobiopterin users, matched for childhood phenylalanine level, had a poorer outcome on some tests than tetrahydrobiopterin users, which might indicate an impact of tetrahydrobiopterin treatment beyond lowering phenylalanine. However, clinical relevance needs further investigation. (PsycINFO Database Record
尽管进行了早期饮食治疗，但与健康对照组相比，苯丙酮尿症患者的智商较低，执行功能较差。苯丙酮尿症患者的认知问题通常与苯丙氨酸水平有关。本研究调查了成年苯丙酮尿症患者的认知概况和心理健康状况，以及与苯丙氨酸水平和四氢生物蝶呤治疗的关系。
57名接受早期治疗的成年苯丙酮尿症患者和57名年龄匹配的健康对照者（18至40岁）进行了阿姆斯特丹神经心理学测试中的智商子测试和执行功能测试。他们还完成了关于心理健康问题的成人自评报告。进行方差分析以检验组间差异。
苯丙酮尿症患者的智商正常，但低于对照组。他们在工作记忆、抑制控制和持续注意力任务上表现较差。患者更频繁地报告有抑郁和回避型人格问题。具体而言，儿童期和终生苯丙氨酸水平≥360μmol/L的患者比对照组的认知和心理健康结果更差。在一部分患者中，对使用和未使用四氢生物蝶呤的患者进行比较，结果显示未使用四氢生物蝶呤的患者（在儿童期、治疗前苯丙氨酸水平匹配）完成任务的速度较慢，且报告有更多心理健康问题。
成年患者的智商低于对照组，执行功能较差，这与在年轻苯丙酮尿症患者中观察到的问题相似，同时还有更多的内化问题。组间差异和苯丙氨酸与结果的关联比在年轻人群中观察到的要小。一部分儿童期苯丙氨酸水平匹配的未使用四氢生物蝶呤的患者在某些测试中的结果比使用四氢生物蝶呤的患者更差，这可能表明四氢生物蝶呤治疗除了降低苯丙氨酸水平外还有其他影响。然而，其临床相关性需要进一步研究。（PsycINFO数据库记录）
