Department of Pediatric Endocrinology/Genetics, Shanghai Institute for Pediatric Research, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neonatal Medicine, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Clin Lab Anal. 2020 Mar;34(3):e23106. doi: 10.1002/jcla.23106. Epub 2019 Nov 24.
Hyperphenylalaninemia is the most common genetic metabolic disease. Early treatment prevents brain injury effectively. The present study aimed to detect the exact amino acid status of patients with hyperphenylalaninemia before treatment.
Data of 116 newborn patients from our Newborn Screening Center and 161 older patients from our clinic before treatment were collected. The content of 17 amino acids in their blood was determined by tandem mass spectrometry and compared with normal controls. Relationship between phenylalanine and other amino acids in patients was analyzed using the smoothing curve fitting and threshold effect analysis.
Most amino acids in the blood of patients were within the normal range; however, they were different significantly from those of the normal children. Newborn patients showed higher phenylalanine (346.30 vs 45.90 µmol/L), valine (121.50 vs 110.30 µmol/L), citrulline, ornithine and lower tyrosine (52.97 vs 66.12 µmol/L), threonine (68.68 vs 78.21 µmol/L), glutamine levels than observed in normal newborns. Older patients showed significantly higher phenylalanine (844.00 vs 51.82 µmol/L), valine (117.60 vs 110.90 µmol/L), histidine, serine and lower tyrosine (55.97 vs 67.31 µmol/L), threonine (35.94 vs 51.89 µmol/L), alanine, asparagine, glutamic acid, methionine, arginine, glycine, ornithine, glutamine content than found in matched normal children. Tyrosine, valine, ornithine, and threonine in newborn patients and tyrosine, glycine, glutamine, and threonine in older patients had a nonlinear correlation with phenylalanine levels with obvious threshold effect and clear inflection points.
Significant difference was observed in the amino acid status between pretherapeutic hyperphenylalaninemia patients and normal children. Some amino acids showed notable threshold effect with phenylalanine level in a nonlinear pattern.
高苯丙氨酸血症是最常见的遗传代谢疾病。早期治疗可有效预防脑损伤。本研究旨在治疗前检测高苯丙氨酸血症患者的确切氨基酸状态。
收集我院新生儿筛查中心 116 例新生儿患者和门诊 161 例治疗前成年患者的资料。采用串联质谱法测定其血中 17 种氨基酸含量，并与正常对照比较。采用平滑曲线拟合和阈值效应分析分析患者苯丙氨酸与其他氨基酸的关系。
患者血中多数氨基酸在正常范围，但与正常儿童有显著差异。新生儿患者血苯丙氨酸（346.30 比 45.90 μmol/L）、缬氨酸（121.50 比 110.30 μmol/L）、瓜氨酸、精氨酸升高，酪氨酸（52.97 比 66.12 μmol/L）、苏氨酸（68.68 比 78.21 μmol/L）、谷氨酰胺降低，与正常新生儿比较差异有统计学意义。成年患者血苯丙氨酸（844.00 比 51.82 μmol/L）、缬氨酸（117.60 比 110.90 μmol/L）、组氨酸、丝氨酸升高，酪氨酸（55.97 比 67.31 μmol/L）、苏氨酸（35.94 比 51.89 μmol/L）、丙氨酸、天冬酰胺、谷氨酸、蛋氨酸、精氨酸、甘氨酸、鸟氨酸、谷氨酰胺降低，与正常儿童比较差异有统计学意义。新生儿患者的酪氨酸、缬氨酸、鸟氨酸和苏氨酸以及成年患者的酪氨酸、甘氨酸、谷氨酰胺和苏氨酸与苯丙氨酸水平呈非线性相关，具有明显的阈值效应和明显的拐点。
治疗前高苯丙氨酸血症患者与正常儿童氨基酸状态存在显著差异。一些氨基酸与苯丙氨酸水平呈非线性关系，具有明显的阈值效应。
