Clinical Application of LC-MS/MS in the Follow-Up for Treatment of Children with Methylmalonic Aciduria

Introduction: To explore the value of high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the follow-up for treatment of children with methylmalonic aciduria (MMA).

Methods: Methylmalonic acid (MMA), 2-methylcitric acid (MCA) and homocysteine (Hcy) were detected by LC-MS/MS in a total of 1016 samples whose estimated 0.5th and 99.5th percentiles was taken as the reference value. The samples of children with MMA and propionic aciduria (PA) who were followed up in our hospital from January 2017 to August 2018 were collected. Samples of dried blood spots, serum, and urine were taken from each patient on the same day. The concentration of the C3 indicator in the dried blood spots was tested by MS/MS. MMA, MCA, and Hcy in the dried blood spots were quantitatively determined by LC-MS/MS, the concentrations of MMA and MCA in urine filter papers were determined by gas chromatography-mass spectrometry (GC/MS), and the concentration of homocysteine in serum was determined by enzymatic cycling assay.

Results: Reference values of MMA, MCA and HCY by LC-MS/MS in the newborn population were determined. The samples from a total of 50 patients were collected, 48 were from children with MMA, and 2 were from children with PA. The first-order equation regression coefficient of MMA in the blood spots and MMA in urine was significant (P < 0.05), r² = 0.736; the first-order equation regression coefficient of MCA in bthe lood spots and MCA in urine was significant (P < 0.05), r² = 0.946; the first-order equation regression coefficient of tHcy in bthe lood spots and Hcy in serum was significant (P < 0.05), r² = 0.771.

Conclusion: LC-MS/MS can be used for the follow-up of children with MMA after treatment, but it is necessary to establish a reference interval suitable for the local population.