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 ( < 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.