MRI Spectroscopy and Neuropsychological Functioning in Phenylketonuria
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Study type: Observational

Summary: 
      This is a study about the relationship of brain biomarkers with neuropsychological
      functioning in PKU. All participants will undergo MRI spectroscopy, will provide a blood
      specimen and will receive neuropsychological testing.
    

Detailed description: 
      Despite newborn screening and early initiation of treatment, many adolescents and adults with
      PKU experience some degree of neuropsychological dysfunction or mood disturbances. Blood
      phenylalanine (Phe) levels and low levels of tyrosine (Tyr) only partially explain why some
      individuals with PKU have these difficulties and others do not. In this study, the
      investigators will use a new approach involving magnetic resonance imaging (MRI) and magnetic
      resonance spectroscopy (MRS) for measuring brain Phe (and other brain chemicals) in order to
      determine relationships between brain biomarkers and neuropsychological functioning and mood.
      Previously, brain Phe and Tyr could not be reliably measured by MRS methods, especially in
      concentrations likely to be found in individuals with treated PKU. This project will use an
      improved method for measuring brain Phe and Tyr. The investigators will use two-dimensional
      shift correlated magnetic resonance spectroscopy (COSY). COSY is a non-invasive method that
      allows for quantitative measurement of Phe, Tyr and other amino acids in the brain. This
      project has the potential to close one of the most important gaps in the knowledge of PKU,
      namely to define how PKU affects the brain. The aims of this study are to examine brain Phe
      and Tyr in individuals with PKU and in an age-matched healthy comparison group, and 2)
      determine the association of Phe and Tyr in distinct brain regions with measures of
      neuropsychological functioning and mood. Participants with PKU will receive 2 MRI scans with
      spectroscopy and the comparison group will receive 1 MRI scan with spectroscopy under fasting
      conditions. All participants will provide a blood specimen for blood amino acid
      determinations and will receive neuropsychological testing. The investigators will develop
      statistical models that can be applied in future studies to enhance understanding of PKU.
      This pilot study is important because it will provide evidence of the usefulness of COSY.
      COSY has the potential to explain individual differences in PKU, identify specific cognitive
      functions or mood disturbances related to high brain Phe or low brain Tyr, and offer an
      additional marker or endpoint for evaluating new treatments in clinical trials.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This is an observational case-controlled study that will include adolescents and young
        adults with PKU (ages 12-25) and a matched comparison group of healthy individuals of the
        same age and sex.
      
Keywords: PKU; Neuropsychology; MRI