NCT07484945

Multiomics Approach in Adult Patients With Phenylketonuria

Relationships Between the Genome and Metabolomic and Phenomic Signatures in Adult Patients With Early-Treated Phenylketonuria: a Multicenter Cross-sectional Study

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 149 (estimated)
• Sponsor: University Hospital, Tours · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU.

Detailed description

• There is a wide clinical variability among PKU patients. Even siblings can present discrepancies regarding the phenotype. The reasons for that are not completely known. There are over 3,300 variants of the PAH gene, some of which influence the severity of the disease, but their impact in adulthood remains poorly understood. Other genes (SLC7A5, HULC, DNAJC12, SHANK family) could also modulate the phenotype. Working Hypotheses: * Some genetic variants influence the severity of neuropsychological and systemic disorders in adults with early-treated PKU. * Metabolomic analysis of sera will identify new biomarkers correlated with the severity of the disease. Methodology: * The study is based on the ECOPHEN cohort (187 adult PKU patients followed for 5 years), of which 150 will provide a DNA sample from saliva for whole-genome sequencing. * Genetic variants will be sought and correlated with clinical, biological, and neuropsychological data. * A non-targeted metabolomic analysis by LC-MS/MS will be performed on the sera, then the metabolic profiles will be associated with phenotypes and genotypes. Objectives and Expected Outcomes: * Better understand the heterogeneity of the disease in adulthood. * Identify associations between genetic variants, metabolic profiles, and clinical evolution. * Pave the way for personalized management and new therapeutic approaches for adult PKU patients.

Conditions

• Phenylketonuria (PKU)

Timeline

• Start date: 2026-03-01
• Primary completion: 2028-03-01
• Completion: 2028-03-01
• First posted: 2026-03-20
• Last updated: 2026-03-20

Locations

15 sites across 1 country: France