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Investigation and Analysis of Blood Biochemical Indexes and Molecular Biology of Methylmalonic Acidemia by DongPo Song, Yanan Lv, Hongqin Wang, Juan Ge, Tang Li, Yanping Chen

Background: To compare MMA-related gene mutations in MMA children and the population in Qingdao, discuss the blood propionyl carnitine (C3), free carnitine (C0) methionine (MET), the mutual ratio and division difference in normal group, carrier group, and MMA group to analyze the relationship between some hotspot mutations and biochemical indicators.
Methods: In total 3,700 newborns testing negative in tandem mass spectrometry (MS/MS) were selected at random and submitted for testing 8 pathogenic sites in MMACHC and 10 in MMUT. The gene mutations in 84 cases with detected mutation genes and 42 diagnosed children were compared. The levels and concentration distribution of C3, C0, MET, C3/C2, C3/C0, C3/MET in the blood samples of three groups were analyzed as well as the difference of biochemical indicators in newborns with hotspot mutations (c.609A>G, c.482G>A, and c.658-660delAAG).
Results: All 8 pathogenic mutations in MMACHC in the population were detected and were basically consistent with the mutation types and frequency order in MMA group. The first three were c.609G>A, c.482G>A, and c.658_660delAAG. There were more types of mutation sites detected in MMA group than carrier group. Five out of 10 MMUT gene mutations were detected in the population, and 9 MMUT gene mutation sites were detected in MMA group. The findings in the two groups and the preset sites were not completely consistent. C3, C0, C3/C2, C3/C0, C3/MET in MMA group were higher than carrier and normal groups, and the difference was statistically significant; the MET in MMA group was lower than carrier and normal groups, and the difference was statistical¬ly significant. Based on the three sets of data distribution graphs, C3, C3/C2, C3/C0, and C3/MET were well distinguished. There were differences in the average C3 and C0 levels between carrier and normal groups, but with an obvious cross distribution in the graphs, and no difference in other indicators. In contrast to non-carrier group, C0, C3, C3/C0, C3/C2, and C3/MET concentration levels were higher in 609A>G mutation group, while MET level was lower, with statistical significance; in c.482G>A mutation group, C3, C3/C0, C3/C2, and C3/MET concentration levels were lower than non-carrier group, while MET level was higher, with statistical significance; in c.658-660delAAG mutation group, C0, C3, C3/C0, C3/C2, MET, and C3/MET concentration levels were not statistically different in contrast to other groups.
Conclusions: The top three mutations in MMA children in Qingdao area are c.609A>G, c.482G>A, c.658-660del AAG mutations in MMAHC; C3, C3/C2, C3/C0 can be used as specific prompt indicators for MMA screening; C3, C3/C2, C3/C0, C3/MET can be used as specific prompt indicators for combined MMA screening; abnormalities in biochemical indicators in hotspot mutation group intuitively explains c.609A>G mutation and early-onset MMA. c.482G>A mutation links with late-onset MMA.

DOI: 10.7754/Clin.Lab.2021.210541