Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels.
Adult early-treated patients
Blood phenylalanine levels
Neuroimaging
Neuropsychological assessment
Phenylketonuria
Volumetry
Journal
Journal of neurodevelopmental disorders
ISSN: 1866-1955
Titre abrégé: J Neurodev Disord
Pays: England
ID NLM: 101483832
Informations de publication
Date de publication:
21 Jun 2024
21 Jun 2024
Historique:
received:
12
03
2024
accepted:
17
06
2024
medline:
22
6
2024
pubmed:
22
6
2024
entrez:
21
6
2024
Statut:
epublish
Résumé
Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce. This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU. Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05). Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67; p = .010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000; p = .008), hippocampus (U = 243.000; p = .020), amygdala (U = 200.000; p = .002), and brainstem (t = 3.17; p = .006) as well as in total cerebral white matter volume (U = 175.000; p = .001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r = -0.417; p = .013) and brainstem (r = -0.455, p = .006) volumes. Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity.
Sections du résumé
BACKGROUND
BACKGROUND
Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce.
OBJECTIVES
OBJECTIVE
This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU.
METHODS
METHODS
Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05).
RESULTS
RESULTS
Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67; p = .010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000; p = .008), hippocampus (U = 243.000; p = .020), amygdala (U = 200.000; p = .002), and brainstem (t = 3.17; p = .006) as well as in total cerebral white matter volume (U = 175.000; p = .001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r = -0.417; p = .013) and brainstem (r = -0.455, p = .006) volumes.
CONCLUSIONS
CONCLUSIONS
Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity.
Identifiants
pubmed: 38907189
doi: 10.1186/s11689-024-09553-w
pii: 10.1186/s11689-024-09553-w
doi:
Substances chimiques
Phenylalanine
47E5O17Y3R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Subventions
Organisme : Ministry of Science and Innovation, Spain
ID : PRE2021-099689
Organisme : Fundació la Marató de TV3
ID : 202014-30-31-32
Organisme : Fundació la Marató de TV3
ID : 202014-30-31-32
Investigateurs
Ana Argudo-Ramírez
(A)
Blanca Barrau-Martínez
(B)
Judith Cantó
(J)
Jaume Campistol
(J)
Francesc Cardellach
(F)
Climent Casals-Pascual
(C)
Gemma Chiva-Blanch
(G)
Dolores García-Arenas
(D)
Francesc Josep García-García
(FJ)
Judit García-Villoria
(J)
José Manuel González de Aledo-Castillo
(JM)
Arnau González-Rodríguez
(A)
Mariona Guitart-Mampel
(M)
Paula Isern
(P)
Amanda Jiménez
(A)
Berta Laudo
(B)
Rafael Llorach
(R)
Félix Andújar-Sánchez
(F)
Rosa López-Galera
(R)
Silvia Mª Meavilla
(SM)
José Cesar Milisenda
(JC)
Blai Morales
(B)
Pedro Juan Moreno-Lozano
(PJ)
Julián Moreno
(J)
Mònica Nos
(M)
Aida Ormazabal
(A)
Montserrat Ortega Ferrer
(M)
Emilio Ortega
(E)
Joan Padrosa
(J)
Abraham José Paredes
(AJ)
Elisa Rubio
(E)
Ester Tobías
(E)
Josep Torremade
(J)
Mireia Urpi-Sarda
(M)
Laura Valls
(L)
Roser Ventura
(R)
Andrea Vergara-Gómez
(A)
Judith Viaplana
(J)
Clara Viñals
(C)
Informations de copyright
© 2024. The Author(s).
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