Toward personalized treatment in phenylketonuria: Intra-individual variation of in vivo phenylalanine oxidation using theC-phenylalanine breath test.
Source: PubMed, NCBI / U.S. National Library of Medicine
With the expanding treatment landscape for phenylketonuria (PKU), there is a growing need for a reliable, non-invasive method to quantify residual phenylalanine hydroxylase (PAH) activity and to determine disease severity to guide individualized treatment strategies. TheC-Phenylalanine (Phe) breath test (C-PBT) has the potential to measure in vivo oxidation of Phe by quantifying conversion ofC-Phe toCO. Although theC-PBT has previously been used in PKU, its test-retest reliability in PAH deficient individuals has not been studied. The aim of this study was to assess the test-retest reliability of theC-PBT in individuals with PAH deficiency and to evaluate the association betweenC-Phe oxidation parameters and disease severity. To establish preliminary reference values and to optimize protocol, 10 healthy adults underwent theC-PBT once. Subsequently, 10 individuals with varying severities of PAH deficiency completed the test twice. After an overnight fast, all participants received an oral dose of 6 mg/kgC-Phe. Both area under the curve (AUC) and the maximumC-Phe oxidation showed a good-to-excellent test-retest reliability, expressed as an ICC of 0.93 (95% CI 0.71-0.98) and 0.91 (95% CI 0.68-0.98) respectively. When stratifying for the genotypic phenotype value (GPV), it was shown that a lower GPV was associated with lower oxidation parameters in comparison to higher GPV levels. These findings support theC-PBT as a reliable, easy to perform, non-invasive measure of in vivo
Abstract
With the expanding treatment landscape for phenylketonuria (PKU), there is a growing need for a reliable, non-invasive method to quantify residual phenylalanine hydroxylase (PAH) activity and to determine disease severity to guide individualized treatment strategies. TheC-Phenylalanine (Phe) breath test (C-PBT) has the potential to measure in vivo oxidation of Phe by quantifying conversion ofC-Phe toCO. Although theC-PBT has previously been used in PKU, its test-retest reliability in PAH deficient individuals has not been studied. The aim of this study was to assess the test-retest reliability of theC-PBT in individuals with PAH deficiency and to evaluate the association betweenC-Phe oxidation parameters and disease severity. To establish preliminary reference values and to optimize protocol, 10 healthy adults underwent theC-PBT once. Subsequently, 10 individuals with varying severities of PAH deficiency completed the test twice. After an overnight fast, all participants received an oral dose of 6 mg/kgC-Phe. Both area under the curve (AUC) and the maximumC-Phe oxidation showed a good-to-excellent test-retest reliability, expressed as an ICC of 0.93 (95% CI 0.71-0.98) and 0.91 (95% CI 0.68-0.98) respectively. When stratifying for the genotypic phenotype value (GPV), it was shown that a lower GPV was associated with lower oxidation parameters in comparison to higher GPV levels. These findings support theC-PBT as a reliable, easy to perform, non-invasive measure of in vivo PAH function that could potentially aid in the interpretation of PAH variants and the assessment of treatment response. TAKE HOME MESSAGE: TheC-Phenylalanine breath test shows good-to-excellent test-retest reliability in adults with phenylalanine hydroxylase deficiency, supporting its potential role as a non-invasive measure of in vivo PAH activity that may aid individualized treatment in PKU.