Abdel-Hamid Mohammed, Tisocki Klara, Sharaf Laila, Ramadan Dina
Department of Pharmaceutical Chemistry , Faculty of Pharmacy, Kuwait University, Safat, Kuwait.
Med Princ Pract. 2007;16(3):215-21. doi: 10.1159/000100393.
The aim of this work was to develop a specific and validated tandem mass spectrometric (MS/MS) method for screening of amino acidopathies, organic acidurias, urea cycle disorders and fatty acid oxidation defects in Kuwaiti newborns and sick infants.
A total of 1,520 blood samples were tested for inborn metabolic disorders in Kuwaiti newborns and sick infants. Positive electrospray MS/MS was used to measure diagnostic acylcarnitines and amino acids in blood spots after simple extraction and derivatization procedures. Validation and stability studies were conducted using control blood samples supplemented with known concentrations of the diagnostic amino acids or acylcarnitines. Reference and cutoff levels of the diagnostic metabolites were determined in a group of 500 normal Kuwaiti babies for quantitative evaluation.
Of the 1,520 samples, 32 were positive newborn cases and 27 positive symptomatic infants. For the validation studies, the range of relative standard deviation was 2.6-14.7%, whereas the range of the percent deviation from nominal concentrations was -23.0 to +25.0 of the diagnostic metabolites. Stability studies indicated appropriate stability of the diagnostic amino acids and acylcarnitines in dried blood spots stored at 22 +/- 1 degrees C and relative humidity of 50-60%.
Tandem mass spectrometry can significantly contribute to a newborn screening program as a fast and highly specific diagnostic technique for screening of a broad range of inborn metabolic disorders.
本研究旨在开发一种特异性强且经过验证的串联质谱（MS/MS）方法，用于筛查科威特新生儿和患病婴儿中的氨基酸代谢病、有机酸尿症、尿素循环障碍及脂肪酸氧化缺陷。
共对1520份科威特新生儿和患病婴儿的血样进行先天性代谢疾病检测。采用正电喷雾MS/MS法，在经过简单提取和衍生化处理后，测定血斑中的诊断性酰基肉碱和氨基酸。使用添加已知浓度诊断性氨基酸或酰基肉碱的对照血样进行验证和稳定性研究。在一组500名正常科威特婴儿中确定诊断性代谢物的参考水平和临界值，用于定量评估。
在1520份样本中，32例为新生儿阳性病例，27例为有症状婴儿阳性。对于验证研究，相对标准偏差范围为2.6% - 14.7%，而诊断性代谢物与标称浓度的偏差百分比范围为 - 23.0%至 + 25.0%。稳定性研究表明，在22±1℃、相对湿度50 - 60%条件下储存的干血斑中，诊断性氨基酸和酰基肉碱具有适当的稳定性。
串联质谱作为一种快速且高度特异的诊断技术，可用于筛查多种先天性代谢疾病，对新生儿筛查项目有显著贡献。
