Yuskiv Nataliya, Saad Ammar, Potter Beth K, Stockler-Ipsiroglu Sylvia, Mitchell John J, Hawken Steven, Tingley Kylie, Pugliese Michael, Lamoureux Monica, Chow Andrea J, Kronick Jonathan B, Wilson Kumanan, Feigenbaum Annette, Goobie Sharan, Inbar-Feigenberg Michal, Little Julian, Mercimek-Andrews Saadet, Pender Amy, Prasad Chitra, Schulze Andreas, Trakadis Yannis, Ho Gloria, Vallance Hilary, Austin Valerie, Vandersteen Anthony, Yu Andrea C, Rockman-Greenberg Cheryl, Mhanni Aizeddin A, Chakraborty Pranesh
Division of Biochemical Genetics, BC Children's Hospital, Department of Pediatrics University of British Columbia Vancouver British Columbia Canada.
School of Epidemiology and Public Health University of Ottawa Ottawa Ontario Canada.
JIMD Rep. 2025 Sep 1;66(5):e70042. doi: 10.1002/jmd2.70042. eCollection 2025 Sep.
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.
实现并维持代谢控制对于苯丙氨酸羟化酶（PAH）缺乏症患儿至关重要。这项回顾性纵向队列研究调查了加拿大12个儿科代谢中心之一接受治疗的PAH缺乏症（≤12岁）患儿的代谢控制情况和监测频率。我们从病历中提取数据，并使用混合效应回归按年龄和诊断分类分析结果。在纳入研究的215名儿童中，43%的病历诊断为经典型苯丙酮尿症（PKU）；其余患儿诊断为轻度PKU或轻度高苯丙氨酸血症（归为“不太严重的PAH缺乏症”）。在出生后的第一个月，经典型PKU患儿的血苯丙氨酸水平在15天的中位年龄时达到120 - 360μmol/L的目标治疗范围，但分别有74.3%和32.9%的患儿有≥1次和≥3次血苯丙氨酸水平低于120μmol/L。从大于1个月到12岁，经典型PKU患儿和不太严重的PAH缺乏症患儿的平均血苯丙氨酸值分别为260.6和236.7μmol/L，血苯丙氨酸水平随年龄增长呈上升趋势（<0.001）。经典型PKU患儿（37.2%）的血苯丙氨酸水平处于治疗范围内的值高于60%的比例低于不太严重的PAH缺乏症患儿（77.9%），表明代谢控制不太理想。血苯丙氨酸检测频率以及与代谢中心的沟通随年龄下降。我们的研究结果表明，需要更好地了解不同年龄和疾病严重程度的患儿血苯丙氨酸水平变化的原因，以便为PAH缺乏症患儿及其照料者提供支持以维持代谢控制。
