TY - JOUR
T1 - Cognitive Profile and Mental Health in Adult Phenylketonuria
T2 - A PKU-COBESO Study
AU - Jahja, Rianne
AU - van der Meere, Jaap J.
AU - Legemaat, Amanda M.
AU - Rubio-Gozalbo, M. Estela
AU - Hofstede, Floris C.
AU - van der Ploeg, Ans T.
AU - Langendonk, Janneke G.
AU - Huijbregts, Stephan C. J.
AU - de Sonneville, Leo M. J.
AU - Bosch, Annet M.
AU - Hollak, Carla E. M.
AU - Brouwers, Martijn C. G. J.
AU - de Vries, Maaike C.
AU - Janssen, Mirian C. H.
AU - van Spronsen, Francjan J.
PY - 2017/5
Y1 - 2017/5
N2 - Objective: 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. Method: 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. Results: 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 mu mol/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. Conclusions: 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.
AB - Objective: 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. Method: 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. Results: 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 mu mol/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. Conclusions: 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.
KW - phenylketonuria
KW - adults
KW - executive functions
KW - mental health
KW - tetrahydrobiopterin
KW - EARLY-TREATED PHENYLKETONURIA
KW - EXECUTIVE FUNCTION IMPAIRMENT
KW - BLOOD PHENYLALANINE LEVELS
KW - TETRAHYDROBIOPTERIN BH4
KW - CHILDREN
KW - ADOLESCENTS
KW - SAPROPTERIN
KW - METAANALYSIS
KW - INDIVIDUALS
KW - INHIBITION
U2 - 10.1037/neu0000358
DO - 10.1037/neu0000358
M3 - Article
C2 - 28318283
SN - 0894-4105
VL - 31
SP - 437
EP - 447
JO - Neuropsychology
JF - Neuropsychology
IS - 4
ER -