title: A Pilot Study of Fluorodeoxyglucose Positron Emission Tomography Findings in Patients with Phenylketonuria before and during Sapropterin Supplementation.
abstract: OBJECTIVE
  PET scanning with fluorodeoxyglucose (FDG-PET) is a non-invasive method that measures regional glucose metabolic rate. Phenylalanine (Phe) and its metabolites appear to impair several aspects of brain energy metabolism. 1) To evaluate brain glucose metabolism with FDG-PET imaging in phenylketonuria (PKU) patients before and 4 months after sapropterin therapy; 2) to evaluate neurodevelopmental changes, blood Phe levels and dietary Phe tolerance before and after sapropterin therapy; 3) to generate pilot data to assess the feasibility of evaluating brain glucose metabolism with FDG-PET imaging and to explore potential trends resulting from the administration of sapropterin therapy.
  
  
  METHODS
  We enrolled 5 subjects, ranged in age from 22 years to 51 years, with PKU. Subjects underwent FDG-PET brain imaging, blood tests for Phe and tyrosine levels, and neurocognitive evaluations before and 4 months after sapropterin therapy (20 mg/kg/day). All subjects' Phe and tyrosine levels were monitored once a week during the study. Subjects kept 3 day diet records that allow calculation of Phe intake.
  
  
  RESULTS
  None of the subjects responded to sapropterin therapy based on 30% decrease in blood Phe level. The data show that glucose metabolism appeared depressed in the cerebellum and left parietal cortex while it was increased in the frontal and anterior cingulate cortices in all five subjects. In response to sapropterin therapy, relative glucose metabolism showed significant increases in left Broca's and right superior lateral temporal cortices. Interestingly, there was corresponding enhanced performance in a phonemic fluency test performed during pre- and postneurocognitive evaluation.
  
  
  CONCLUSIONS
  Further studies with a larger sample size are needed to confirm the above changes in both sapropterin non-responsive and responsive PKU patients.
authors.affiliation: Children's Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, Section of Biochemical Genetics, Philadelphia, PA, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Ficicioglu
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Dubroff
authors.forename: Nina
authors.initials: N
authors.lastname: Thomas
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gallagher
authors.forename: Jessica
authors.initials: J
authors.lastname: Burfield
authors.forename: Christie
authors.initials: C
authors.lastname: Hussa
authors.forename: Rebecca
authors.initials: R
authors.lastname: Randall
authors.forename: Hongming
authors.initials: H
authors.lastname: Zhuang
keywords: fluorodeoxyglucose positron emission tomography; phenylketonuria; sapropterin
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