Rapid diagnosis and early specific treatment of metabolic epilepsies due to inborn errors of metabolism (IEMs) is crucial to avoid irreversible sequalae. Nowadays, besides the profile analysis of amino‐ and organic acids, a range of additional targeted assays is used for the selective screening of those diseases. This strategy can lead to long turn‐around times, repeated sampling and diagnostic delays. To replace those individual targeted assays, we developed a new liquid chromatography mass spectrometry method (LC‐MS/MS) for the differential diagnosis of inherited metabolic epilepsies that are potentially treatable. The method was developed to simultaneously quantify 12 metabolites (sulfocysteine, guanidinoacetate, creatine, pipecolic acid, Δ¹‐piperideine‐6‐carboxylate (P6C), proline, Δ¹‐pyrroline‐5‐carboxylate (P5C), and the B₆‐vitamers) enabling the diagnosis of nine different treatable IEMs presenting primarily with early‐onset epilepsy. Plasma and urine samples were mixed with internal standards, precipitated and the supernatants were analyzed by LC‐MS/MS. In comparison with previous assays, no derivatization of the metabolites is necessary for analysis. This LC‐MS method was validated for quantitative results for all metabolites except P6C and P5C for which semiquantitative results were obtained due to the absence of commercially available standards. Coefficients of variation for all analytes were below 15% and recovery rates range between 80% and 120%. Analysis of patient samples with known IEMs demonstrated the diagnostic value of the method. The presented assay covers a selected panel of biochemical markers, improves the efficiency in the laboratory, and potentially leads to faster diagnoses and earlier treatment avoiding irreversible damage in patients affected with IEMs.

中文翻译：

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LC-MS/MS 方法用于可治疗的早发性遗传性代谢性癫痫的鉴别诊断。

由于先天性代谢障碍 (IEM) 导致的代谢性癫痫的快速诊断和早期特异性治疗对于避免不可逆的后遗症至关重要。如今，除了氨基酸和有机酸的概况分析外，还使用一系列额外的靶向检测来选择性筛查这些疾病。这种策略会导致周转时间长、重复采样和诊断延迟。为了取代那些单独的靶向检测，我们开发了一种新的液相色谱质谱法 (LC-MS/MS)，用于鉴别诊断可能治疗的遗传性代谢性癫痫。的方法被开发用于同时定量12种代谢物（硫代半胱氨酸，guanidinoacetate，肌酸，2-哌啶酸，Δ ¹ -piperideine -6-羧酸乙酯（P6C），脯氨酸，Δ ¹-吡咯啉-5-羧酸盐（P5C）和B ₆‐vitamers) 能够诊断九种不同的可治疗 IEM，主要表现为早发性癫痫。血浆和尿液样品与内标混合，沉淀，上清液通过 LC-MS/MS 进行分析。与以前的分析相比，分析不需要对代谢物进行衍生化。除了 P6C 和 P5C 外，由于缺乏市售标准品，因此获得了半定量结果，该 LC-MS 方法已对所有代谢物的定量结果进行了验证。所有分析物的变异系数均低于 15%，回收率介于 80% 和 120% 之间。使用已知 IEM 分析患者样本证明了该方法的诊断价值。所提出的检测涵盖了一组选定的生化标记，提高了实验室的效率，