Multiomics Approach in Adult Patients With Phenylketonuria

• 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.

Inclusion criteria

• PKU patients over the age of 18,
• diagnosed through the newborn screening program,
• patients who participated in the final visit of the ECOPHEN study,
• affiliation with a health insurance plan,
• informed consent dated and signed by patients for DNA analysis (saliva sample)

Exclusion criteria

• Patients whose PKU diagnosis was not detected during neonatal screening,
• Patients who have not signed a dated informed consent form,
• Patients who are unable to provide a saliva sample.