Multiomics (genome plus metabolome) approach for adults with phenylketonuria

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

This project will test whether combining whole-genome sequencing from saliva and non-targeted blood metabolomics can find genetic and metabolic patterns linked to symptoms in adults who were treated for phenylketonuria from birth.

Quick facts

• Study type: Observational
• Enrollment: 149 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Tours (other)
• Locations: 15 sites (Angers and 14 other locations)
• Trial ID: NCT07484945 on ClinicalTrials.gov

What this trial studies

Adults with early-treated phenylketonuria (PKU) show wide clinical variability that is not fully explained by known PAH gene variants, and other modifier genes may influence adult outcomes. The project will use the ECOPHEN cohort, collecting saliva for whole-genome sequencing from about 150 participants and performing non-targeted LC-MS/MS metabolomic profiling on serum samples. Genetic variants and metabolic profiles will be correlated with clinical, biological, and neuropsychological data to identify genotype–phenotype relationships and candidate biomarkers. Results are intended to clarify disease heterogeneity in adulthood and inform more personalized management and potential therapeutic targets.

Who should consider this trial

Good fit: Adults (18 or older) with PKU diagnosed by newborn screening who participated in the ECOPHEN final visit, have health insurance, can provide informed consent, and are able to give a saliva sample.

Not a fit: Patients diagnosed after the neonatal period, children under 18, or those unable to provide a saliva sample or consent are unlikely to benefit from this specific protocol.

Why it matters

Potential benefit: If successful, this work could identify biomarkers and genetic modifiers that enable more personalized care and new treatment strategies for adults with PKU.

How similar studies have performed: Prior PKU research has shown some PAH genotype–phenotype links and small metabolomics studies have suggested candidate biomarkers, but combining whole-genome sequencing and non-targeted serum metabolomics in adult PKU is largely novel.

Eligibility criteria

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.

Where this trial is running

Angers and 14 other locations

• University hospital — Angers, France (NOT_YET_RECRUITING)
• University hospital — Bordeaux, France (NOT_YET_RECRUITING)
• University hospital — Brest, France (NOT_YET_RECRUITING)
• University hospital — Dijon, France (NOT_YET_RECRUITING)
• University hospital — Grenoble, France (NOT_YET_RECRUITING)
• University hospital — Lille, France (NOT_YET_RECRUITING)
• Civil Hospitals — Lyon, France (NOT_YET_RECRUITING)
• Conception hospital — Marseille, France (NOT_YET_RECRUITING)
• University hospital — Nancy, France (NOT_YET_RECRUITING)
• University hospital — Nantes, France (NOT_YET_RECRUITING)
• Necker hospital — Paris, France (NOT_YET_RECRUITING)
• University hospital — Rennes, France (NOT_YET_RECRUITING)
• University hospital — Saint-Etienne, France (NOT_YET_RECRUITING)
• University hospital — Toulouse, France (NOT_YET_RECRUITING)
• university hospital, Tours — Tours, France (RECRUITING)

Study contacts

• Principal investigator: Yannick MOUPATAM-NGAMBY-ADRIAASEN, Sir — University, Tours
• Study coordinator: François MAILLOT, Pr

Conditions: Phenylketonuria, saliva, genetics