Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second‐tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long‐term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and the C3/C2, C3/C16 ratios. The disease burden showed a direct correlation with MCA and FGF21, for both diseases. All transplanted patients showed a significant reduction of MCA in comparison to baseline values, with some differences dependent on the type of transplantation. Our study provided new insights in understanding the disease pathophysiology, showing similarities between MCA and FGF21 in predicting disease burden, long‐term complications and in evaluating the impact of organ transplantation.

中文翻译：

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血浆甲基柠檬酸及其与其他疾病生物标志物的相关性：对丙酸和甲基丙二酸血症患者随访的影响。

甲基柠檬酸（MCA）分析主要用于丙酸盐疾病的诊断或作为新生儿筛查的二级检测，但其对患者监测的效用仍有待确定。我们探讨了 MCA 在有机酸尿症的长期管理中的潜在贡献。我们前瞻性地评估了标准治疗和/或移植后 22 名患者的血浆 MCA 及其与疾病生物标志物、临床状态和疾病负担的关系，其中 13 名患有丙酸血症 (PA)，9 名患有甲基丙二酸血症 (MMA)。在预定的常规对照或代谢失代偿 (MD) 发作期间收集样品，移植后对 10 名患者进行评估（6 名肝脏，2 名肝肾联合，2 名肾脏）。与 MMA 相比，PA 中的 MCA 水平更高，并且其水平不受临床状态（MD 与健康状态）的影响。在 MMA 中，老年患者的 MCA 较高，并且与成纤维细胞生长因子 21 (FGF21) 和血浆甲基丙二酸一起与 GFR 呈负相关。在这两种疾病中，MCA 与氨、甘氨酸、赖氨酸、C3 和 C3/C2、C3/C16 比率相关。对于这两种疾病，疾病负担都与 MCA 和 FGF21 直接相关。与基线值相比，所有移植患者的 MCA 均显着降低，部分差异取决于移植类型。我们的研究为理解疾病病理生理学提供了新见解，显示了 MCA 和 FGF21 在预测疾病负担、长期并发症和评估器官移植影响方面的相似性。