| Objective: Our study aimed to investigate the clinical significance and application value of serum fibroblast growth factor 21(FGF21)and growth differentiation factor 15(GDF15)in the diagnosis of primary mitochondrial diseases in children.Methods: We recruited patients diagnosed with primary mitochondrial disease,non-mitochondrial neuromuscular disease as disease controls and healthy children as healthy controls from Children’s Hospital of Chongqing Medical University from 2016 to 2017.And the clinical data and blood samples of the children were collected.The serum levels of FGF21 and GDF15 were measured by ELISA.The clinical data,laboratory examination results,serum FGF21 and GDF15 levels,MDC mitochondrial disease score(Morava Mitochondrial disease criteria,MDC)and International pediatric mitochondrial disease scale(International pediatric mitochondrial disease scale,IPMDS)were analyzed to compare the differences of each biomarkers in different groups.Calculate the sensitivity,specificity,negative predictive value,negative predictive value,diagnostic odds ratio(OR),ROC curve,etc.of each marker to study the value of FGF21 and GDF15 in the screening and diagnosis of primary mitochondrial diseases;Spearman rank correlation analysis evaluated the influencing factors of FGF21 and GDF15 and their relationship with disease diagnosis score and prognosis score.Results: Of the 51 patients with mitochondrial disease,50 were diagnosed by clinical manifestations and genetic diagnosis,and 1 was diagnosed by clinical manifestations and muscle pathological biopsy.The median age was 36.0 months(11.0-96.0 months).The median age was 36.0months(11.0-96.0 months).In accordance with the principle of matching the age and gender of patients with mitochondrial diseases,the case control group was selected from patients with non-mitochondrial neuromuscular diseases who were in the Department of Neurology.A total of 30 patients,with a median age of 61.5 months(34.8-84.0 months)were selected.50 volunteers with normal physical examinations in the physical examination center of our hospital were included in the healthy control group,with a median age of 37.0 months(21.0-58.3 months).Through statistical analysis:1.The average levels of serum FGF21 and GDF15 in the mitochondrial disease group were 3.3 times and 4.2 times that of the healthy control group,and 2.0 times and 3.1 times that of the disease control group.The difference was statistically significant(P<0.05);2.Sensitivity: GDF15>lactic acid>FGF21>lactic acid/pyruvate;specificity: lactic acid/pyruvate> FGF21> lactic acid> GDF15;diagnostic efficacy: GDF15>lactic acid>FGF21>lactic acid/pyruvate;3.Calculated by the maximum Youden index,the critical value of FGF21 is 151.160 pg/ml,and the corresponding specificity and sensitivity are 85% and 72.5% respectively;when the critical value of GDF15 is606.369 pg/ml,the corresponding sensitivity and specificity are 74.5%,100% respectively;4.Through the analysis between groups,it was found that FGF21 increased most significantly in the non-skeletal muscle affected group or the gastrointestinal affected group;GDF15 increased most significantly in the multi-organ function affected group;and there is no difference OF the two indicators between whether the sensory organs were involved or not,different mutation type(mt DNA/n DNA),different mutation gene function type,syndrome/non-syndrome and different syndrome phenotypes;5.Spearman correlation analysis found that FGF21,GDF15 and age,lactate and GDF15,lactate and MDC score,FGF21 and IPMDS are positively correlated.Conclusion: The value of serum GDF15 in the diagnosis of primary mitochondrial diseases is higher than that of FGF21 and the current clinically commonly used serum lactic acid,lactic acid/pyruvate,and can be used as the first choice of biological markers for screening and diagnosis of primary mitochondrial diseases in children.The level of serum FGF21 is correlated with the severity of the disease. |
PDF Full Text Request