Cognitive profile and mental health in adult phenylketonuria: A PKU-COBESO study.
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.


METHODS
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 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.


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. (PsycINFO Database Record
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen.
Rianne
R
Jahja
Department of Clinical Child and Adolescent Studies, Leiden University.
Stephan C J
SCJ
Huijbregts
Department of Clinical Child and Adolescent Studies, Leiden University.
Leo M J
LMJ
de Sonneville
Department of Developmental and Clinical Neuropsychology, University of Groningen.
Jaap J
JJ
van der Meere
Department of Developmental and Clinical Neuropsychology, University of Groningen.
Amanda M
AM
Legemaat
Academic Medical Center.
Annet M
AM
Bosch
Academic Medical Center.
Carla E M
CEM
Hollak
University Hospital Maastricht.
M Estela
ME
Rubio-Gozalbo
Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, University Hospital Maastricht.
Martijn C G J
MCGJ
Brouwers
Wilhelmina Children's Hospital, University Medical Center Utrecht.
Floris C
FC
Hofstede
University Medical Center St. Radboud Nijmegen.
Maaike C
MC
de Vries
University Medical Center St. Radboud Nijmegen.
Mirian C H
MCH
Janssen
Erasmus Medical Center.
Ans T
AT
van der Ploeg
Erasmus Medical Center.
Janneke G
JG
Langendonk
Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen.
Francjan J
FJ
van Spronsen
D000293:Adolescent; D000328:Adult; D001288:Attention; D001708:Biopterins / Q000031:analogs & derivatives / Q000627:therapeutic use; D003071:Cognition; D003863:Depression / Q000209:etiology / Q000523:psychology; D056344:Executive Function; D005260:Female; D006304:Health Status; D006801:Humans; D007266:Inhibition, Psychological; D007361:Intelligence Tests; D008297:Male; D008570:Memory, Short-Term; D008603:Mental Health; D010554:Personality Disorders / Q000209:etiology / Q000523:psychology; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000188:drug therapy / Q000523:psychology*; D057566:Self Report; D055815:Young Adult
D001708:Biopterins; D010649:Phenylalanine; C003402:sapropterin