PDF(Pubmed)
Abstract：
UNASSIGNED: Routine metabolic assessments for methylmalonic acidemia (MMA), propionic acidemia (PA), and homocysteinemia involve detecting metabolites in dried blood spots (DBS) and analyzing specific biomarkers in serum and urine. This study aimed to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous detection of three specific biomarkers (methylmalonic acid, methylcitric acid, and homocysteine) in DBS, as well as to appraise the applicability of these three DBS metabolites in monitoring patients with MMA, PA, and homocysteinemia during follow-up.
UNASSIGNED: A total of 140 healthy controls and 228 participants were enrolled, including 205 patients with MMA, 17 patients with PA, and 6 patients with homocysteinemia. Clinical data and DBS samples were collected during follow-up visits.
UNASSIGNED: The reference ranges (25th-95th percentile) for DBS methylmalonic acid, methylcitric acid, and homocysteine were estimated as 0.04-1.02 μmol/L, 0.02-0.27 μmol/L and 1.05-8.22 μmol/L, respectively. Following treatment, some patients achieved normal metabolite concentrations, but the majority still exhibited characteristic biochemical patterns. The concentrations of methylmalonic acid, methylcitric acid, and homocysteine in DBS showed positive correlations with urine methylmalonic acid (r = 0.849, p < 0.001), urine methylcitric acid (r = 0.693, p < 0.001), and serum homocysteine (r = 0.721, p < 0.001) concentrations, respectively. Additionally, higher levels of DBS methylmalonic acid and methylcitric acid may be associated with increased cumulative complication scores.
UNASSIGNED: The LC-MS/MS method established in this study reliably detects methylmalonic acid, methylcitric acid, and homocysteine in DBS. These three DBS metabolites can be valuable for monitoring patients with MMA, PA, and homocysteinemia during follow-up. Further investigation is required to determine the significance of these DBS biomarkers in assessing disease burden over time.
UNASSIGNED: A total of 140 healthy controls and 228 participants were enrolled, including 205 patients with MMA, 17 patients with PA, and 6 patients with homocysteinemia. Clinical data and DBS samples were collected during follow-up visits.
UNASSIGNED: The reference ranges (25th-95th percentile) for DBS methylmalonic acid, methylcitric acid, and homocysteine were estimated as 0.04-1.02 μmol/L, 0.02-0.27 μmol/L and 1.05-8.22 μmol/L, respectively. Following treatment, some patients achieved normal metabolite concentrations, but the majority still exhibited characteristic biochemical patterns. The concentrations of methylmalonic acid, methylcitric acid, and homocysteine in DBS showed positive correlations with urine methylmalonic acid (r = 0.849, p < 0.001), urine methylcitric acid (r = 0.693, p < 0.001), and serum homocysteine (r = 0.721, p < 0.001) concentrations, respectively. Additionally, higher levels of DBS methylmalonic acid and methylcitric acid may be associated with increased cumulative complication scores.
UNASSIGNED: The LC-MS/MS method established in this study reliably detects methylmalonic acid, methylcitric acid, and homocysteine in DBS. These three DBS metabolites can be valuable for monitoring patients with MMA, PA, and homocysteinemia during follow-up. Further investigation is required to determine the significance of these DBS biomarkers in assessing disease burden over time.
摘要：
■甲基丙二酸血症（MMA）的常规代谢评估，丙酸血症(PA),和同型半胱氨酸血症涉及检测干血斑（DBS）中的代谢物以及分析血清和尿液中的特定生物标志物。本研究旨在建立液相色谱-串联质谱(LC-MS/MS)同时检测三种特异性生物标志物(甲基丙二酸,甲基柠檬酸,和高半胱氨酸）在DBS中，以及评估这三种DBS代谢物在监测MMA患者中的适用性，PA,随访期间的同型半胱氨酸血症。
■共纳入140名健康对照和228名参与者，包括205名MMA患者，17名PA患者，和6例同型半胱氨酸血症患者。在随访期间收集临床数据和DBS样品。
■DBS甲基丙二酸的参考范围（第25-95百分位数），甲基柠檬酸,同型半胱氨酸估计为0.04-1.02μmol/L，0.02-0.27μmol/L和1.05-8.22μmol/L,分别。治疗后,一些患者达到正常的代谢物浓度，但大多数仍然表现出特征性的生化模式。甲基丙二酸的浓度,甲基柠檬酸,DBS中同型半胱氨酸与尿甲基丙二酸呈正相关(r=0.849,p<0.001),尿甲基柠檬酸（r=0.693，p<0.001），和血清同型半胱氨酸（r=0.721，p<0.001）浓度，分别。此外,较高水平的DBS甲基丙二酸和甲基柠檬酸可能与累积并发症评分增加相关.
■本研究中建立的LC-MS/MS方法可靠地检测甲基丙二酸，甲基柠檬酸,DBS中的同型半胱氨酸。这三种DBS代谢物可用于监测MMA患者，PA,随访期间的同型半胱氨酸血症。需要进一步的研究来确定这些DBS生物标志物在评估随时间的疾病负担中的重要性。
■共纳入140名健康对照和228名参与者，包括205名MMA患者，17名PA患者，和6例同型半胱氨酸血症患者。在随访期间收集临床数据和DBS样品。
■DBS甲基丙二酸的参考范围（第25-95百分位数），甲基柠檬酸,同型半胱氨酸估计为0.04-1.02μmol/L，0.02-0.27μmol/L和1.05-8.22μmol/L,分别。治疗后,一些患者达到正常的代谢物浓度，但大多数仍然表现出特征性的生化模式。甲基丙二酸的浓度,甲基柠檬酸,DBS中同型半胱氨酸与尿甲基丙二酸呈正相关(r=0.849,p<0.001),尿甲基柠檬酸（r=0.693，p<0.001），和血清同型半胱氨酸（r=0.721，p<0.001）浓度，分别。此外,较高水平的DBS甲基丙二酸和甲基柠檬酸可能与累积并发症评分增加相关.
■本研究中建立的LC-MS/MS方法可靠地检测甲基丙二酸，甲基柠檬酸,DBS中的同型半胱氨酸。这三种DBS代谢物可用于监测MMA患者，PA,随访期间的同型半胱氨酸血症。需要进一步的研究来确定这些DBS生物标志物在评估随时间的疾病负担中的重要性。
