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

This study has been completed.
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Information provided by (Responsible Party):
Children's Hospital Boston Identifier:
First received: August 5, 2013
Last updated: July 21, 2014
Last verified: July 2014

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.

Condition Intervention
Other: MRI

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: The Brain, Neurological Features and Neuropsychological Functioning in Adults With Phenylketonuria: A Pilot Study

Resource links provided by NLM:

Further study details as provided by Children's Hospital Boston:

Primary Outcome Measures:
  • phenylalanine level in the brain as determined by MR Spectroscopy [ Time Frame: one time only ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Full scale intelligence quotient (IQ) [ Time Frame: One time ] [ Designated as safety issue: No ]
  • Electroencephalogram (EEG) findings [ Time Frame: One time ] [ Designated as safety issue: No ]
  • Volumetric MRI findings [ Time Frame: One time ] [ Designated as safety issue: No ]
  • Diffusion tensor imaging (DTI) findings through MRI [ Time Frame: One time ] [ Designated as safety issue: No ]
  • Tremor as determined through neurological evaluation [ Time Frame: One time ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: August 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Adults with PKU
MRI, EEG, neuropsychological testing, neurological examination, blood draw, diet diary, physical examination
Other: MRI


Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Male and Female adults with PKU


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.


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


  Contacts and Locations
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Please refer to this study by its identifier: NCT01917344

United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Children's Hospital Boston
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Principal Investigator: Susan E Waisbren, PhD Children's Hospital Boston
  More Information

No publications provided

Responsible Party: Children's Hospital Boston Identifier: NCT01917344     History of Changes
Other Study ID Numbers: IRB-P00003864
Study First Received: August 5, 2013
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Boston:
Neuropsychological functioning
Neurological functioning

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases processed this record on May 27, 2015