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Neurological and psychiatric issues in 187 adults with early-treated PKU: The ECOPHEN study
Chloé Giret1, Sybil Charrière2, François Feillet3
1Service de Médecine Interne, Centre de Référence des Maladies Héréditaires du Métabolisme, CHU de Tours, Tours, France.
Insights
Adults with early-treated phenylketonuria (PKU) often experience persistent neurological and psychiatric issues, even with good diet adherence. Lifelong monitoring is crucial for managing these neurocognitive deficits and ensuring better long-term outcomes.
Area of Science:
- Neuroscience
- Genetics
- Metabolic Disorders
Background:
- Phenylketonuria (PKU) is an inherited metabolic disorder caused by PAH gene mutations, leading to phenylalanine buildup.
- Early diagnosis via newborn screening allows for dietary or sapropterin treatment, preventing severe intellectual disability.
- Long-term outcomes in adults with early-treated PKU, including subtle neurocognitive deficits and psychiatric complications, require further characterization.
Purpose of the Study:
- To assess neuropsychiatric disorders in adults with early-treated PKU.
- To investigate the impact of PKU severity and diet adherence on neurological and psychiatric outcomes.
Main Methods:
- The ECOPHEN study was a 5-year French multicenter prospective cohort.
- 187 patients with early-treated PKU were recruited and classified by PKU severity and diet adherence.
- Data on neurological history, examination, and psychiatric issues were collected at inclusion.
Main Results:
- Neurological symptoms (tremor, migraines, balance disorders) occurred in 11.2% of classic PKU patients.
- Abnormal deep tendon reflexes were common in classic PKU patients during neurological examination.
- Psychiatric issues, mainly depression and anxiety, affected 25.7% of patients across all severity groups.
Conclusions:
- Neurological complications persist in adults with early-treated PKU, especially classic forms.
- Diet adherence and plasma Phe levels did not significantly correlate with outcomes, suggesting potential suboptimal metabolic control.
- Adults with early-treated PKU require lifelong neurological and psychiatric follow-up due to the risk of neuropsychiatric manifestations.
Introduction:
Phenylketonuria (PKU) is an autosomal recessive disorder caused by mutations in the PAH gene leading to phenylalanine hydroxylase deficiency. This results in the accumulation of phenylalanine (Phe) in blood and brain, causing neurological and psychiatric impairments if untreated. Newborn screening (NBS) introduced in the 1960s enables early PKU diagnosis, allowing prompt dietary or sapropterin treatment. The long-term outcomes in adults with early-treated PKU, however, may include subtle neurocognitive deficits alongside somatic neurological and psychiatric complications, which remain incompletely characterized.
Patients And Methods:
The ECOPHEN study was a French 5-year multicenter prospective cohort assessing neuropsychiatric disorders in adults with early-treated PKU.
Results:
Here are presented the data at inclusion. The study recruited 187 patients who were classified by PKU severity-classic, mild, or mild persistent hyperphenylalaninemia-and diet adherence status. Neurological history revealed symptoms in 11.2 % of patients, exclusively in classic PKU, including tremor, migraines, and balance disorders, without significant differences between diet groups. Neurological examination abnormalities predominantly included abnormal deep tendon reflexes in classic PKU patients. Psychiatric issues affected 25.7 % of patients across severity groups, mainly depressive episodes and anxiety, with no clear influence of diet adherence.
Discussion/Conclusion:
The present study highlights neurological complications persisting despite early treatment, particularly in classic PKU. Diet adherence and current plasma Phe levels did not correlate significantly with neurological or psychiatric outcomes, possibly due to suboptimal metabolic control. Limitations included the cross-sectional design, absence of control group, and retrospective data collection. Overall, adults with early-treated PKU show a generally favorable outcome but remain at risk for neuropsychiatric manifestations, supporting the need for lifelong follow-up including neurologic and psychiatric evaluation.
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