Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study

Achieving and maintaining metabolic control is critical for children with phenylalanine hydroxylase (PAH) deficiency. This retrospective longitudinal cohort study investigated metabolic control and monitoring frequency of children with PAH deficiency (≤ 12 years) treated at one of 12 pediatric metabolic centres across Canada. We abstracted data from medical charts and analyzed outcomes by age and diagnostic classification, using mixed effects regression. Of 215 children included in the study, 43% had a chart diagnosis of classic phenylketonuria (PKU); the remainder had a diagnosis of mild PKU or mild hyperphenylalaninemia (grouped as "less severe PAH deficiency"). During the first month of life, blood phenylalanine levels of children with classic PKU reached the target therapeutic range of 120-360 μmol/L at a median age of 15 days, but 74.3% and 32.9% had ≥ 1 and ≥ 3 values below 120 μmol/L, respectively. From age > 1 month to 12 years, mean blood phenylalanine values were 260.6 and 236.7 μmol/L for children with classic PKU and less severe PAH deficiency, respectively, with a trend of increased blood phenylalanine levels with increasing age (<i>p</i> < 0.001). Fewer children with classic PKU (37.2%) versus less severe PAH deficiency (77.9%) had > 60% of values in the therapeutic range, indicating less optimal metabolic control. Frequency of blood phenylalanine testing and communication with metabolic centres decreased with age. Our findings suggest a need to better understand the reasons for blood phenylalanine variability across child age and disease severity in order to inform supports for children with PAH deficiency and their caregivers to maintain metabolic control.

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Publication Details

Journal
JIMD Reports
Published
2025-09-01
DOI
https://doi.org/10.1002/jmd2.70042
Primary Topic
Metabolism and Genetic Disorders
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article
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article

Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study

Andreas Schulze, Pranesh K. Chakraborty, Yannis Trakadis, Valerie Austin et al.
JIMD Reports
Metabolism and Genetic Disorders
article

Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study

Andreas Schulze, Pranesh K. Chakraborty, Yannis Trakadis, Valerie Austin, Hilary Vallance, Kumanan Wilson, Kylie Tingley, Michael Pugliese, Steven Hawken, Cheryl R. Greenberg, Nataliya Yuskiv, Andrea Chow, Amy Pender, Sylvia Stöckler‐Ipsiroglu, Ammar Saad, Monica Lamoureux, Beth K. Potter, Julian Little, Andrea C. Yu, Sharan Goobie, John J. Mitchell, Michal Inbar‐Feigenberg, Saadet Mercimek‐Andrews, Annette Feigenbaum, Anthony Vandersteen, Aizeddin A. Mhanni, Chitra Prasad, Gloria Ho, Jonathan B. Kronick
article en

Abstract

Achieving and maintaining metabolic control is critical for children with phenylalanine hydroxylase (PAH) deficiency. This retrospective longitudinal cohort study investigated metabolic control and monitoring frequency of children with PAH deficiency (≤ 12 years) treated at one of 12 pediatric metabolic centres across Canada. We abstracted data from medical charts and analyzed outcomes by age and diagnostic classification, using mixed effects regression. Of 215 children included in the study, 43% had a chart diagnosis of classic phenylketonuria (PKU); the remainder had a diagnosis of mild PKU or mild hyperphenylalaninemia (grouped as "less severe PAH deficiency"). During the first month of life, blood phenylalanine levels of children with classic PKU reached the target therapeutic range of 120-360 μmol/L at a median age of 15 days, but 74.3% and 32.9% had ≥ 1 and ≥ 3 values below 120 μmol/L, respectively. From age > 1 month to 12 years, mean blood phenylalanine values were 260.6 and 236.7 μmol/L for children with classic PKU and less severe PAH deficiency, respectively, with a trend of increased blood phenylalanine levels with increasing age (<i>p</i> < 0.001). Fewer children with classic PKU (37.2%) versus less severe PAH deficiency (77.9%) had > 60% of values in the therapeutic range, indicating less optimal metabolic control. Frequency of blood phenylalanine testing and communication with metabolic centres decreased with age. Our findings suggest a need to better understand the reasons for blood phenylalanine variability across child age and disease severity in order to inform supports for children with PAH deficiency and their caregivers to maintain metabolic control.

JIMD ReportsVol. 66(5)
Western University (CA), Dalhousie University (CA), University of British Columbia (CA), University of Ottawa (CA), University of Alberta (CA), University of Toronto (CA), Children's Hospital of Eastern Ontario (CA), Montreal Children's Hospital (CA), Izaak Walton Killam Health Centre (CA), Ottawa Hospital (CA), London Health Sciences Centre (CA), Hospital for Sick Children (CA), McGill University Health Centre (CA), McMaster Children's Hospital (CA), Nova Scotia Health Authority (CA), Rady Children's Hospital-San Diego (US), Children's Hospital Research Institute of Manitoba (CA), SickKids Foundation (CA), Bruyère (CA), BC Children's Hospital (CA), Ottawa Hospital Research Institute (CA), University of Manitoba (CA), McGill University (CA)
Canadian Institutes of Health Research
Openalex Percentile: Top 74%
Metabolism and Genetic Disorders
DOIOpen Access PDFOpenAlex
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