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Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase
Nataliya Yuskiv1, Ammar Saad2, Beth K Potter2
1Division of Biochemical Genetics, BC Children's Hospital, Department of Pediatrics University of British Columbia Vancouver British Columbia Canada.
Insights
Maintaining metabolic control in children with phenylalanine hydroxylase (PAH) deficiency is crucial. This study found that metabolic control and monitoring frequency decline with age in children with PAH deficiency, highlighting a need for improved support.
Area of Science:
- Metabolic Disorders
- Pediatric Endocrinology
- Genetics and Rare Diseases
Background:
- Phenylalanine hydroxylase (PAH) deficiency, including phenylketonuria (PKU), requires lifelong metabolic control.
- Effective management is critical for preventing neurodevelopmental complications in affected children.
- Understanding factors influencing metabolic control across different age groups and disease severities is essential.
Purpose of the Study:
- To investigate metabolic control and monitoring frequency in Canadian children with PAH deficiency up to 12 years of age.
- To analyze outcomes based on age and diagnostic classification (classic PKU vs. less severe PAH deficiency).
- To identify trends in blood phenylalanine levels and testing frequency over time.
Main Methods:
- Retrospective longitudinal cohort study involving 215 children from 12 Canadian pediatric metabolic centers.
- Data abstracted from medical charts, including blood phenylalanine levels and monitoring frequency.
- Mixed effects regression analysis used to examine outcomes by age and diagnostic group.
Main Results:
- Children with classic PKU reached therapeutic phenylalanine levels later than ideal and showed significant variability.
- Mean blood phenylalanine levels increased with age in both classic PKU and less severe PAH deficiency groups (p < 0.001).
- Fewer children with classic PKU (37.2%) achieved optimal metabolic control compared to those with less severe deficiency (77.9%).
- Frequency of blood phenylalanine testing and communication with metabolic centers decreased as children aged.
Conclusions:
- Metabolic control in children with PAH deficiency is challenging to maintain, particularly in those with classic PKU and as they age.
- Decreasing monitoring frequency with age suggests a potential gap in ongoing care and support.
- Further research is needed to understand phenylalanine variability and develop targeted interventions for sustained metabolic control.
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 (p < 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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