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

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.

Study Overview

• Status: Completed
• Conditions: Phenylketonuria
• Intervention / Treatment: Other: MRI

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult with classic PKU who has been seen at one of the hospitals collaborating in this study
2. Age 18-55 years
3. 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.)
4. Capable of providing informed consent
5. Able to undergo MRI procedures without sedating medication
6. Does not have metal implants

7. Not currently on Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trials.

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Exclusion Criteria:

1. Mild PKU or mild hyperphenylalaninemia
2. Less than 18 years old or great than 55 years old
3. No medical records available for the first 6 years of life
4. No record of genotype
5. Not capable of providing informed consent
6. Not able to undergo MRI without sedating medication
7. Has metal implants

8. Currently taking Kuvan, Large Neutral Amino Acid therapy or involved in any clinical trial

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Adults with PKU; 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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Boston Children's Hospital
• Collaborators: Beth Israel Deaconess Medical Center; Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): June 1, 2014

Study Registration Dates

• First Submitted: August 5, 2013
• First Submitted That Met QC Criteria: August 5, 2013
• First Posted (ESTIMATE): August 6, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): June 19, 2015
• Last Update Submitted That Met QC Criteria: June 2, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: MRI; EEG; Phenylketonuria; Neuropsychological functioning; Neurological functioning
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: IRB-P00003864