6 research outputs found
PKU.CAT
No full textCONSORTIUM PKU.CATThe Consortium PKU.CAT began in 2021 as a private-public partnership under the leadership of Dr. Josep M Grau-Junyent, Dra. Glòria Garrabou, Dra. Aida Ormazabal, Dra. Carme Junqué and Dra. Bàrbara Segura. The PKU.CAT is an interdisciplinary healthcare team of basic and clinical researchers, who belong to different universities (Universitat de Barcelona), medical (Hospital Clínic de Barcelona, Hospital Sant Joan de Déu) and research centers (Fundació Clínic per la Recerca Biomèdica, Institut d'Investigacions Biomèdiques Pi i Sunyer, Sant Joan de Déu Institut de Recerca) in Barcelona, Catalonia (Spain), devoted to the assistance of patients with phenylalanine disorders. PKU.CAT final aim is to improve the quality of life of the affected patients and their families, to change the natural history of the disease, and to gain further insight into the causes of poor clinical outcomes, both cardiovascular and neurological.La Marató de TV3 Foundation promoted the main body of research of this Consortium, which has been focused on cardiovascular risk assessment, through an investment of 322.992,0 €: PHENYLKETONURIA: FROM CHILDHOOD TO ADULTS THROUGH BRAIN FUNCTIONAL CONNECTOMICS, CARDIOVASCULAR CHANGES, METABOLOMIC AND INTESTINAL MICROBIOTA CHARACTERISTICS (starting date 20/05/2021). A current list of the whole membership can be found here: * Hospital Clínic – IDIBAPS – Fundació Clínic per la Recerca Biomèdcia: Argudo-Ramírez, Ana; Cantó, Judith; Cardellach, Francesc; Casals-Pascual, Climent; Chiva-Blanch, Gemma; Forga-Visa, Maria de Talló; García-García, Francesc Josep; García-Villoria, Judit; Garrabou, Glòria; González de Aledo-Castillo, José Manuel; Grau-Junyent, Josep M; Guitart-Mampel, Mariona; Isern, Paula; Jiménez, Amanda; Laudo, Berta; Andújar-Sánchez, Félix; López-Galera, Rosa Mª; Milisenda, José Cesar; Montserrat-Carbonell, Cristina; Morales, Blai; Moreno-Lozano, Pedro Juan; Moreno, Julián; Nos, Mònica; Ortega Ferrer, Montserrat; Ortega, Emilio; Padrosa, Joan; Pané, Adriana; Paredes, Abraham José; Rubio, Elisa; Tobías, Ester; Torremade, Josep; Valls, Laura; Ventura, Roser; Vergara-Gómez, Andrea; Viaplana, Judith; Viñals, Clara.* Hospital Sant Joan de Déu – Fundació Sant Joan de Déu: Campistol, Jaume; García-Arenas, Dolores; Meavilla, Silvia; Ormazabal, Aida. * Universitat de Barcelona: Barrau-Martínez, Blanca; Capdevila-Lacasa, Clara; González-Rodríguez, Arnau; Junqué, Carme; Llorach, Rafael; Pardo, Jessica; Segura, Barbara; Urpi-Sarda, Mireia.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria
No full textBackground
Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI).
Methods
Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data.
Results
Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected).
Conclusions
Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance
Nutritional and Metabolic Signatures in Pediatric Phenylketonuria and Hyperphenylalaninemia: Insights from Untargeted Urinary Metabolomics.
No full textDietary interventions are essential for managing phenylketonuria (PKU) and may influence metabolic regulation beyond phenylalanine control. We characterized the urinary metabolomic fingerprint of pediatric participants (n = 82) recruited into clinical phenotypes: PKU, PKU with response to tetrahydrobiopterin (BH4), and hyperphenylalaninemia (HPA), as well as sex- and age-matched healthy children controls. Untargeted metabolomics (HPLC-Q-TOF-MS/MS) revealed 59 discriminant metabolites across multiple biochemical pathways, including phenylalanine, tryptophan, and caffeine metabolisms, as well as metabolites related to dietary exposure or gut microbial metabolism. Distinct urinary signatures were described across phenotypes. phenylalanine-related pathways predominated in PKU, accompanied by increased excretion of vitamin derivatives, consistent with protein substitute supplementation. In contrast, reduced levels of non-phenylalanine amino acid derivatives, methylhistidines, creatine, and branched-chain amino acid-related metabolites were observed in PKU, suggesting alterations in muscle metabolism or natural protein intake. Microbiota-derived metabolites were also less represented in PKU, indicating potential effects of dietary restrictions on gut-host metabolic interactions. HPA individuals showed a urinary fingerprint closer to controls, whereas the BH4 subgroup exhibited the greatest metabolic heterogeneity, reflecting variability in dietary and pharmacological treatment responses. These findings reveal metabolic diversity within the pediatric PKU spectrum driven by clinical phenotype and nutritional management. Urinary metabolomics may support more precise monitoring of metabolic health status and guide precision nutrition strategies in PKU and HPA from early life
Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels
No full textBackground: 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: This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU.
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: 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: 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
Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels
No full textAbstract 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 This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU. 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 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 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
Untargeted Metabolomic Study for Urinary Characterization of Adult Patients with Phenylketonuria.
No full textPhenylketonuria (PKU) is a rare inherited metabolic disorder caused by phenylalanine hydroxylase deficiency, leading to phenylalanine (Phe) accumulation and neurological dysfunction if untreated. While metabolomics holds promise for biomarker discovery in PKU, few studies have examined urinary metabolites using untargeted approaches. This study applied untargeted metabolomics using HPLC-QTOF-MS to analyze urine from 36 adult patients with PKU and 34 healthy controls. Biomarker Analysis was performed with MetaboAnalyst 6.0. A total of 73 significant metabolites (FDR 1) were identified, with 29 upregulated and 44 downregulated in PKU. A 23% of these metabolites were related to Phe metabolism, while 77% were associated with alterations across more than 10 metabolic pathways, including leucine and tryptophan metabolism, acylcarnitines, vitamins, and diet- or microbiota-derived compounds, among others. Specifically, upregulated metabolites with an AUC > 0.9 included several Phe-derived compounds, the nucleoside 8-hydroxy-7-methylguanine, and indole compounds (1H-indole-3-carboxaldehyde). Conversely, downregulated metabolites with an AUC > 0.9 included N-acetyl(iso)leucine and a heptenoylcarnitine isomer. The Random Forest-based model demonstrated enhanced predictive performance when integrating 10 metabolites, supporting their potential utility as biomarkers for PKU. These findings improve the biological understanding of metabolic disturbances beyond Phe, and may support the development of new therapeutic and dietary strategies
