TY - JOUR
T1 - Long-Term Follow-Up of Cognition and Mental Health in Adult Phenylketonuria
T2 - A PKU-COBESO Study
AU - Jahja, Rianne
AU - van Spronsen, Francjan J.
AU - de Sonneville, Leo M. J.
AU - van der Meere, Jaap J.
AU - Bosch, Annet M.
AU - Hollak, Carla E. M.
AU - Rubio-Gozalbo, M. Estela
AU - Brouwers, Martijn C. G. J.
AU - Hofstede, Floris C.
AU - de Vries, Maaike C.
AU - Janssen, Mirian C. H.
AU - van der Ploeg, Ans T.
AU - Langendonk, Janneke G.
AU - Huijbregts, Stephan C. J.
PY - 2017/9
Y1 - 2017/9
N2 - Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0-12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 A mu mol/L in childhood and phenylalanine ae360 A mu mol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylalanine ae360 A mu mol/L throughout life (n = 7), supporting the notion that phenylalanine should be below the recommended upper treatment target of 360 A mu mol/L during childhood for better outcome in adulthood. Despite some results indicating additional influence of phenylalanine levels between 13 and 17 years of age, evidence for a continued influence of phenylalanine levels after childhood on adult outcomes was largely lacking. This may be explained by the fact that the patients in the present study had relatively low phenylalanine levels during childhood (mean: 330 A mu mol/L, range: 219-581 A mu mol/L) and thereafter (mean Index of Dietary Control at T2: 464 A mu mol/L, range: 276-743 A mu mol/L), which may have buffered against transitory periods of poor metabolic control during adolescence and early adulthood.
AB - Cognitive and mental health problems in individuals with the inherited metabolic disorder phenylketonuria (PKU) have often been associated with metabolic control and its history. For the present study executive functioning (EF) was assessed in 21 PKU patients during childhood (T1, mean age 10.4 years, SD = 2.0) and again in adulthood (T2, mean age 25.8 years, SD = 2.3). At T2 additional assessments of EF in daily life and mental health were performed. Childhood (i.e. 0-12 years) blood phenylalanine was significantly related to cognitive flexibility, executive motor control, EF in daily life and mental health in adulthood (i.e. at T2). Patients with a greater increase in phenylalanine levels after the age of 12 performed more poorly on EF-tasks at T2. Group-based analyses showed that patients with phenylalanine <360 A mu mol/L in childhood and phenylalanine ae360 A mu mol/L from age 13 onwards (n = 11) had better cognitive flexibility and executive motor control than those who had phenylalanine ae360 A mu mol/L throughout life (n = 7), supporting the notion that phenylalanine should be below the recommended upper treatment target of 360 A mu mol/L during childhood for better outcome in adulthood. Despite some results indicating additional influence of phenylalanine levels between 13 and 17 years of age, evidence for a continued influence of phenylalanine levels after childhood on adult outcomes was largely lacking. This may be explained by the fact that the patients in the present study had relatively low phenylalanine levels during childhood (mean: 330 A mu mol/L, range: 219-581 A mu mol/L) and thereafter (mean Index of Dietary Control at T2: 464 A mu mol/L, range: 276-743 A mu mol/L), which may have buffered against transitory periods of poor metabolic control during adolescence and early adulthood.
KW - Phenylketonuria
KW - Executive functioning
KW - Executive motor control
KW - Mental health
KW - Adults
KW - Longitudinal
KW - EARLY-TREATED PHENYLKETONURIA
KW - PHENYLALANINE CONCENTRATIONS
KW - EXECUTIVE FUNCTION
KW - ADOLESCENTS
KW - METAANALYSIS
KW - INHIBITION
KW - DIAGNOSIS
KW - SYMPTOMS
KW - BEHAVIOR
KW - OUTCOMES
U2 - 10.1007/s10519-017-9863-1
DO - 10.1007/s10519-017-9863-1
M3 - Article
C2 - 28776207
SN - 0001-8244
VL - 47
SP - 486
EP - 497
JO - Behavior Genetics
JF - Behavior Genetics
IS - 5
ER -