Multiomics Approach in Adult Patients With Phenylketonuria
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- This is an observational study: the protocol does not assign a study treatment.
- Who it may be relevant to
- Registry conditions: Phenylketonuria (PKU). Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Relationships Between the Genome and Metabolomic and Phenomic Signatures in Adult Patients With Early-Treated Phenylketonuria: a Multicenter Cross-sectional Study
Overview
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.
Primary outcome measures
- Identification of metabolite clusters [Time frame: Enrolment]
- Identification of genetic variants DNAJC12, HULC, SLC7A5, and SHANK and other ones [Time frame: Enrolment]
Secondary outcome measures (7)
- Number of patients with neurological complications [Time frame: Enrolment]
- average intelligence quotient (IQ) [Time frame: Enrolment]
- California Verbal Learning Test [Time frame: Enrolment]
- Trail Making Test [Time frame: Enrolment]
- Beck Depression Inventory [Time frame: Enrolment]
- Weight changes [Time frame: Time of enrollment]
- Bone mineral density changes [Time frame: Enrolment]
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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Case-only
Study locations
France · 15 centers
- University hospital — Angers
- University hospital — Bordeaux
- University hospital — Brest
- University hospital — Dijon
- University hospital — Grenoble
- University hospital — Lille
- Civil Hospitals — Lyon
- Conception hospital — Marseille
- … and 7 more centers
Identifiers
NCT: NCT07484945 · DR250249 - GENOPHEN