TY - JOUR
T1 - The effect of improved dietary control on cognitive and psychiatric functioning in adults with phenylketonuria
T2 - the ReDAPT study
AU - Burgess, Nicholas M.
AU - Kelso, Wendy
AU - Malpas, Charles B.
AU - Winton-Brown, Toby
AU - Fazio, Timothy
AU - Panetta, Julie
AU - De Jong, Gerard
AU - Neath, Joanna
AU - Atherton, Sonny
AU - Velakoulis, Dennis
AU - Walterfang, Mark
PY - 2021/1/18
Y1 - 2021/1/18
N2 - Background: Phenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase. Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals who discontinue dietary control subsequently suffer symptoms of anxiety, depression and disturbances to cognition. We undertook a prospective cohort study of patients with early-treated phenylketonuria who had ceased dietary control to test the hypothesis that resumption of dietary control of PKU is associated with improvements in measures of psychiatric morbidity and cognitive functioning. Methods: We re-initiated dietary control for early-treated patients with PKU and monitored cognitive and psychiatric outcomes over a twelve-month period. Assessments included objective cognitive function (measured by cognitive proficiency index (CPI)), anxiety and depression scales. General linear mixed model (GLMM) analyses were performed to assess change in psychometric variables from baseline over twelve months after resumption of dietary control. Results: A total of nine patients were recruited. Mean age was 33 years (SD = 8.75), five were female. Mean time off dietary control was 19.1 years (SD = 11.3), and mean baseline phenylalanine (Phe) levels were 1108 µmol/L (SD = 293). GLMM analysis demonstrated a positive relationship between CPI and time on diet (b = 0.56 [95% CI = 0.17, 0.95]). Age, time off diet, Phe levels and depression scores were not associated with cognitive function. There was a negative relationship between time on diet and anxiety (b = − 0.88 95% CI = [− 1.26, − 0.50]) and depression ratings (b = − 0.61, 95% CI = [− 0.95, − 0.26]). Conclusions: This study demonstrated improvements in cognitive function, anxiety, and depression ratings associated with resumption of dietary control of PKU. Raw Phe levels were not strongly associated with psychiatric or cognitive scores in this cohort. These findings support the importance of lifelong treatment for PKU in improving the cognitive and psychiatric sequelae of the disease.
AB - Background: Phenylketonuria (PKU) is an autosomal recessive inherited disorder characterised by a deficiency in phenylalanine hydroxylase. Untreated, PKU is associated with a wide range of cognitive and psychiatric sequelae. Contemporary management guidelines recommend lifetime dietary control of phenylalanine (Phe) levels, however many individuals who discontinue dietary control subsequently suffer symptoms of anxiety, depression and disturbances to cognition. We undertook a prospective cohort study of patients with early-treated phenylketonuria who had ceased dietary control to test the hypothesis that resumption of dietary control of PKU is associated with improvements in measures of psychiatric morbidity and cognitive functioning. Methods: We re-initiated dietary control for early-treated patients with PKU and monitored cognitive and psychiatric outcomes over a twelve-month period. Assessments included objective cognitive function (measured by cognitive proficiency index (CPI)), anxiety and depression scales. General linear mixed model (GLMM) analyses were performed to assess change in psychometric variables from baseline over twelve months after resumption of dietary control. Results: A total of nine patients were recruited. Mean age was 33 years (SD = 8.75), five were female. Mean time off dietary control was 19.1 years (SD = 11.3), and mean baseline phenylalanine (Phe) levels were 1108 µmol/L (SD = 293). GLMM analysis demonstrated a positive relationship between CPI and time on diet (b = 0.56 [95% CI = 0.17, 0.95]). Age, time off diet, Phe levels and depression scores were not associated with cognitive function. There was a negative relationship between time on diet and anxiety (b = − 0.88 95% CI = [− 1.26, − 0.50]) and depression ratings (b = − 0.61, 95% CI = [− 0.95, − 0.26]). Conclusions: This study demonstrated improvements in cognitive function, anxiety, and depression ratings associated with resumption of dietary control of PKU. Raw Phe levels were not strongly associated with psychiatric or cognitive scores in this cohort. These findings support the importance of lifelong treatment for PKU in improving the cognitive and psychiatric sequelae of the disease.
KW - Anxiety
KW - Cognitive function
KW - Depression
KW - Diet
KW - Phenylketonuria
KW - Processing speed
UR - http://www.scopus.com/inward/record.url?scp=85100122262&partnerID=8YFLogxK
U2 - 10.1186/s13023-020-01668-2
DO - 10.1186/s13023-020-01668-2
M3 - Article
C2 - 33461585
AN - SCOPUS:85100122262
SN - 1750-1172
VL - 16
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
IS - 1
M1 - 35
ER -