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The GENOPHEN study aims to explore the links between the genome, metabolomic profile, and clinical phenotype in adults with early-treated PKU.
• 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:
Methodology:
Objectives and Expected Outcomes:
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| Measure | Description | Time Frame |
|---|---|---|
| Identification of metabolite clusters | untargeted metabolomic analysis of plasma samples collected during the ECOPHEN study Phenylalanine level (> 900 µmol/L, 900-600 µmol/L, < 600 µmol/L), response to BH4 (Complete response: decrease in Phe levels after treatment leading to normalization of Phe levels; partial response: 30% decrease without normalization; non-responder: decrease of less than 30% in Phe levels.) | Enrolment |
| Identification of genetic variants DNAJC12, HULC, SLC7A5, and SHANK and other ones | genome sequencing of DNA collected from saliva samples during the GENOPHEN study. The DNAJC12, HULC, SLC7A5, and SHANK (SHANK1, SHANK2, and SHANK3) variants will be listed and classified as frequent (allele frequency > 1%) or rare (allele frequency < 1%) according to the gnomAD database. The same will apply to other variants potentially identified by genome sequencing. | Enrolment |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with neurological complications | Enrolment | |
| average intelligence quotient (IQ) | WAIS IV results identified in the ECOPHEN cohort study (>= 130 : Very superior; 120-129 Superior; 110-119 High average; 90-109 Average; 80-89 : Low average; 70-79 Borderline; =< 69 Extremely low) |
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Inclusion Criteria:
Exclusion Criteria:
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PKU adult patients
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| François MAILLOT, Pr | Contact | 2.47.47.37.15 | +33 | francois.maillot@univ-tours.fr |
| Name | Affiliation | Role |
|---|---|---|
| Yannick MOUPATAM-NGAMBY-ADRIAASEN, Sir | University, Tours | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University hospital | Not yet recruiting | Angers | 49000 | France |
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| ID | Term |
|---|---|
| D010661 | Phenylketonurias |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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Saliva
| Enrolment |
| California Verbal Learning Test | CVLT results identified in the ECOPHEN cohort study. There is no minimum or maximum score; it is a "raw" score. | Enrolment |
| Trail Making Test | TMT results identified in the ECOPHEN cohort study. This is the number of seconds it takes to finish connecting the points on a "path" consisting of 25 points; the lower the number, the better (the patient is faster), but there isn't really a minimum and no maximum. | Enrolment |
| Beck Depression Inventory | BDI test results identified in the ECOPHEN cohort study The score ranges from 0 to 63, with the following qualitative interpretations: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression | Enrolment |
| Weight changes | Body mass index (Kg/m2) | Time of enrollment |
| Bone mineral density changes | Bone mineral density, measured by DWA, expressed as Z-scores | Enrolment |
| University hospital | Not yet recruiting | Bordeaux | 33000 | France |
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| University hospital | Not yet recruiting | Brest | 29000 | France |
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| University hospital | Not yet recruiting | Dijon | 21000 | France |
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| University hospital | Not yet recruiting | Grenoble | 38000 | France |
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| University hospital | Not yet recruiting | Lille | 59000 | France |
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| Civil Hospitals | Not yet recruiting | Lyon | 69000 | France |
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| Conception hospital | Not yet recruiting | Marseille | 13000 | France |
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| University hospital | Not yet recruiting | Nancy | 54000 | France |
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| University hospital | Not yet recruiting | Nantes | 44000 | France |
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| Necker hospital | Not yet recruiting | Paris | 75000 | France |
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| University hospital | Not yet recruiting | Rennes | 35000 | France |
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| University hospital | Not yet recruiting | Saint-Etienne | 42000 | France |
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| University hospital | Not yet recruiting | Toulouse | 31000 | France |
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| university hospital, Tours | Recruiting | Tours | 37044 | France |
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| D009422 | Nervous System Diseases |
| D000592 | Amino Acid Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |