查看更多>>摘要：? 2021 Elsevier B.V.Background: Recent studies have indicated that N-acetyl-leucine (N-Ac-Leu) is a potential biomarker of diabetes. This study aimed to measure the levels of enantiomers of the chiral molecule N-Ac-DL-Leu in the saliva of patients with type 2 diabetes and further determine the potential association between them. Method: A novel validated method was established using ultra-performance liquid chromatography (UPLC) with fluorescence (FL) detection, in which precolumn derivatization of (R)-(-)-4-(N, N-dimethylaminosulfonyl)-7-(3-aminopyrrolidin-l-yl)-2,1,3-benzoxadiazole [(R)-(-)-DBD-APy] was used for the simultaneous determination and chiral separation of N-Ac-DL-Leu in human saliva. Results: The labeled N-Ac-DL-Leu diastereomers were completely separated, with a resolution value of 1.93. Additionally, excellent linearity for N-Ac-DL-Leu was observed, with high coefficients of correlation (r2 ≥ 0.9999) in the range of 10–300 μM; the limit of quantitation (signal-to-noise ratio = 10) was 40–120 pmol/mL, and the mean recoveries of N-Ac-L-Leu and N-Ac-D-Leu were 102.48% and 104.68%, respectively. The levels of N-Ac-Leu in the saliva of diabetic patients and healthy volunteers were determined, and it was found that the levels of N-Ac-DL-Leu in the saliva of diabetic patients were significantly lower than those in healthy volunteers. (p < 0.01). Conclusions: The proposed method was successfully applied for the measurement of N-Ac-DL-Leu enantiomers in the saliva of diabetic patients and healthy volunteers.
查看更多>>摘要：? 2021 Elsevier B.V.The mitochondrial translation optimization factor 1(MTO1) gene mutations had been reported to be linked to combined oxidative phosphorylation defificiency-10 (COXPD10). In this study, we presented the detailed clinical features and genetic analysis of the patient with two variants in MTO1, and reviewed 42 different cases available in publications. Whole exome sequencing and bioinformatics analysis were employed to detect the genetic variants of a 6-month-old boy with metabolic disorder and multiple organ failure; Sanger sequencing was performed to confirm the origin of variants; and clinical data of the patients was retrospectively collected and analyzed. Variant classification was followed to ACMG guidline. The proband was diagnosed with multiple organ failure, severe pneumonia, sepsis, hyperlactatemia, metabolic acidosis, and moderate anemia. Compound heterozygous mutations in the coding region of MTO1 gene (c.1291C > T/p.Arg431Trp and c.1390C > T/p.Arg464Cys) were identified, and the results of family verification experiment showed that the mutations were inherited from the parents, respectively. Combined with clinical symptoms, the patient was diagnosed as COXPD10. In summary, hallmark features of MTO1 mutations were lactic acidosis and hypertrophic cardiomyopathy. Of note, patients with the same genetic mutation may not have the same clinical presentation. Additional MTO1 defificiency cases will help to make genotype-phenotype correlations clearer.
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