血乳酸 FGF21在儿童线粒体脑肌病诊断与疗效监测中作用及意义

doi:10.3969/j.issn.1006-6233.2024.05.010

Abstract
Figure/Table
References
Related Citation (15)

Download: PDF (1621 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To analyze the role and significance of blood lactate and fibroblast growth factor 21 (FGF21) in the diagnosis and efficacy monitoring of mitochondrial myopathy (ME) in children. Methods: A total of 141 subjects were enrolled in this study, including 47 children with ME (ME group), 47 children with non-mitochondrial myopathies (muscle disease group), and 47 healthy children (control group), all of whom were admitted to Kunming Children's Hospital from August 2020 to February 2023. The ME group received dietary and exercise guidance, lamotrigine, idebenone, vitamin C, folic acid, and coenzyme Q10 for treatment. The efficacy was evaluated 3 months after treatment, and the ME patients were divided into controlled and uncontrolled subgroups according to the efficacy. Fasting blood samples were collected before treatment, 1 month after treatment, and 3 months after treatment. Blood lactate levels were measured using the American YSI 1500 SPORT blood lactate analyzer and matching reagent kit, and serum FGF21 levels were measured using enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent assay (ELISA). The levels of blood lactate and FGF21 in the three groups before treatment were compared. The interaction coefficient γ and OR values were used to analyze the interaction of blood lactate and FGF21 on the susceptibility of children to ME. The receiver operating characteristic (ROC) curve was used to analyze the value of blood lactate and FGF21 in the diagnosis of ME in children. The changes in blood lactate, FGF21, and Newcastle Mitochondrial Disease Assessment Scale (NMDAS) scores before and after treatment were compared between ME patients with different efficacies. Pearson correlation analysis was used to analyze the correlation between the decrease in blood lactate and FGF21 after 1 month and 3 months of treatment and the decrease in NMDAS score. Results: Compared with the control group, the levels of blood lactate and FGF21 were elevated in the ME group (t=13.901, 38.082, P<0.05); compared with the muscle disease group, the levels of blood lactate and FGF21 were also elevated in the ME group (t=12.734, 35.696, P<0.05); there was no significant difference in blood lactate and FGF21 levels between the control group and the muscle disease group (t=0.821, 1.326, both P>0.05); interaction analysis showed that the OR value caused by the coexistence of blood lactate and FGF21 was 1350.500, the regression coefficient was 7.208, the interaction OR value was less than the product of the OR values of the two single factors, which was a sub-multiplicative model, γ=1.535>1, and the effect of blood lactate on FGF21 had a positive interaction effect; ROC curve showed that the AUC of blood lactate + FGF21 for the diagnosis of ME in children was 0.904, which was higher than that of blood lactate (0.839) and FGF21 (0.719), with a diagnostic sensitivity of 78.72% and a specificity of 87.23%; the levels of blood lactate, FGF21 and NMDAS scores in patients with controlled disease were lower than those in patients with uncontrolled disease after 1 month and 3 months of treatment (P<0.05); correlation analysis showed that the decrease in blood lactate and FGF21 after 1 month and 3 months of treatment was positively correlated with the decrease in NMDAS score after 1 month and 3 months of treatment (P<0.05). Conclusion: The blood lactate and FGF21 levels in children with ME are elevated, and there is a positive interaction between the two, which is closely related to the condition and efficacy of the disease.

Key words： Blood lactate FGF21 Children Mitochondrial encephalomyopathy Diagnosis Efficacy monitoring

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors

Cite this article:

URL:

http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.05.010 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I7/1114

[1] Ng YS,Lax NZ,Blain AP,et al.Forecasting stroke-like episodes and outcomes in mitochondrial disease[J].Brain,2022,145(2):542-554.
[2] Kimonis V,Al Dubaisi R,Maclean AE,et al.NUBPL mitochondrial disease:new patients and review of the genetic and clinical spectrum[J].Med Genet,2021,58(5):314-325.
[3] Hirano M,Carelli V,De Giorgio R,et al.Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE):position paper on diagnosis,prognosis,and treatment by the MNGIE International Network[J].Inherit Metab Dis,2021,44(2):376-387.
[4] Povea-Cabello S,Villanueva-Paz M,Villalon-Garcia I,et al.Modeling mitochondrial encephalomyopathy,lactic acidosis,and stroke-like episodes syndrome using patient-derived induced neurons generated by direct reprogramming[J].Cell Reprogram,2022,24(5):294-303.
[5] Keipert S,Ost M.Stress-induced FGF21 and GDF15 in obesity and obesity resistance[J].Trends Endocrinol Metab,2021,32(11):904-915.
[6] Zhang IW,Curto A,Lopez-Vicario C,et al.Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure.[J].Hepatol,2022,76(1):93-106.
[7] Burtscher J,Soltany A,Visavadiya NP,et al.Mitochondrial stress and mitokines in aging[J].Aging Cell,2023,22(2):13770.
[8] 中华医学会神经病学分会,中华医学会神经病学分会神经肌肉病学组,中华医学会神经病学分会肌电图与临床神经生理学组.中国神经系统线粒体病的诊治指南[J].中华神经科杂志,2015,48(12):1045-1051.
[9] Montano V,Lopriore P,Gruosso F,et al.Primary mitochondrial myopathy:12-month follow-up results of an Italian cohort[J].Neurol,2022,269(12):6555-6565.
[10] Sharma R,Reinstadler B,Engelstad K,et al.Circulating markers of NADH-reductive stress correlate with mitochondrial disease severity[J].Clin Invest,2021,131(2):136055.
[11] 杨倩,符跃强.GTPBP3基因变异相关线粒体病1例报告并文献复习[J].临床儿科杂志,2021,39(11):818-821.
[12] Lehtonen JM,Auranen M,Darin N,et al.Diagnostic value of serum biomarkers FGF21 and GDF15 compared to muscle sample in mitochondrial disease[J].Inherit Metab Dis,2021,44(2):469-480.
[13] Wesot-Kucharska D,Rokicki D,Greczan M,et al.The fibroblast growth factor 21 concentration in children with mitochondrial disease does not depend on the disease stage,but rather on the disease genotype[J].Pediatr Endocrinol Diabetes Metab,2022,28(2):141-151.
[14] Riley LG,Nafisinia M,Menezes MJ,et al.FGF21 outperforms GDF15 as a diagnostic biomarker of mitochondrial disease in children[J].Mol Genet Metab,2022,135(1):63-71.