The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study

Study Overview
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Brief Summary
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Newborn screening and early treatment prevent the most severe manifestations of phenylketonuria (PKU). However, executive functioning deficits, attention deficit disorder, slow processing speed, and visual-motor problems commonly occur. Many adults with this disorder also suffer depression and anxiety. Using advanced electroencephalogram (EEG) and magnetic resonance imaging (MRI) techniques, including novel MR spectroscopy (MRS) we hope to discover why this distinct constellation of deficits occurs in PKU. Adult subjects with PKU will undergo EEG and comprehensive MRI evaluations, including a novel method of MR spectroscopy to determine brain phenylalanine levels. In addition, they will receive neurological and neuropsychological examinations and dietary evaluation.

Official Title
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The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study

Conditions
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Phenylketonuria

Intervention / Treatment
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* Other: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult with classic PKU who has been seen at one of the hospitals collaborating in this study Age 18-55 years Medical Records available that include genotype and blood phenylalanine levels during the first 6 years of life. (We have over 300 patients with PKU with genotypes in our clinic, of whom about half are adults.) Capable of providing informed consent Able to undergo MRI procedures without sedating medication Does not have metal implants Not currently on Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trials. - Exclusion Criteria: Mild PKU or mild hyperphenylalaninemia Less than 18 years old or great than 55 years old No medical records available for the first 6 years of life No record of genotype Not capable of providing informed consent Not able to undergo MRI without sedating medication Has metal implants Currently taking Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trial -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Adults with PKU<br>MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination. These activities were performed for the study, but no drug or other interventions took place. | Other: MRI<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phenylalanine Level in the Brain as Determined by MR Spectroscopy and in Blood | Brain Phe levels (umol/L) using MRI correlated spectroscopy and Blood Phe levels (umol/L) obtained on the same day. | During period of evaluation, approximately 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Full Scale Intelligence Quotient (IQ) |  | During period of evaluation, approximately 8 hours | 
| Electroencephalogram (EEG) Findings |  | During period of evaluation, approximately 8 hours | 
| Volumetric MRI Findings |  | During period of evaluation, approximately 8 hours | 
| Diffusion Tensor Imaging (DTI) Findings Through MRI |  | During period of evaluation, approximately 8 hours | 
| Tremor as Determined Through Neurological Evaluation |  | During period of evaluation, approximately 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Phenylketonuria, Neuropsychological functioning, Neurological functioning, EEG