J Clin Neurol.  2013 Jul;9(3):151-156. 10.3988/jcn.2013.9.3.151.

A Pilot Study of Fluorodeoxyglucose Positron Emission Tomography Findings in Patients with Phenylketonuria before and during Sapropterin Supplementation

• Ficicioglu C
• Dubroff JG
• Thomas N
• Gallagher
• Burfield J
• Hussa C
• Randall R
• Zhuang H

• KMID: 2287553
• DOI: http://doi.org/10.3988/jcn.2013.9.3.151

Abstract

BACKGROUND AND PURPOSE
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.

Keyword

phenylketonuria; sapropterin; fluorodeoxyglucose positron emission tomography

MeSH Terms

Biopterin
Brain
Cerebellum
Diet Records
Electrons
Energy Metabolism
Glucose
Hematologic Tests
Humans
Neuroimaging
Phenylalanine
Phenylketonurias
Pilot Projects
Positron-Emission Tomography
Sample Size
Tyrosine
Biopterin
Glucose
Phenylalanine
Tyrosine

Figure

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  Fig. 1 Representative [F-18] FDG-PET transaxial images throughout the cortices (A, C, E and G) and mid-brain (B, D, F and H). [F-18] FDG-PET regions of interest are shown in (A) and (B) as determined by Philips NeuroQ (version 3.0) as well as corresponding locations in a representative normal brain (C and D) and one of this study's participants before (E and F) and after (G and H) Sapropterin supplementation (126 days). Note the purple shaded region in (A) designates Broca's area in which a significant increase in glucose metabolism was found in response to therapy. Tracer uptake intensity color legend is shown to the right of the images (red/yellow=highest, black/violet=lowest). Note the depressed glucose metabolism in the frontal cortices relative to the parietal cortices in the PKU patient (E-H) compared to the normal example (C and D). This pattern was present in all patients. FDG-PET: fluorodeoxyglucose positron emission tomography.

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