Biomechanical Characteristics of Peripheral Blood Mononuclear Ceils in Mitochondrial Diabetes Caused by mt.3243A ＞ G Mutation / 医学研究杂志

Objective To explore the surface morphological and biomechanical properties differences of peripheral blood mononuclear cells (PBMCs) between groups of patients with mitochondrial diabetes caused by mt.3243A ＞ G mutation and healthy controls.Methods 2 milliliters blood were obtained from each subject of the mitochondrial diabetes group (n =5) and the control group (n =5).The PBMCs were separated from the blood using the standard Ficoll-Hypaque density-gradient centrifugation method and detected by atomic force microscope (AFM).Results The morphological analysis revealed that compared with control group,the PBMCs of diabetic patients tended to have a lower cell height (0.73 ± 0.24μm vs 2.49 ± 1.17μm,P =0.011) and a much rougher cell membrane (Ra:161.8 ± 33.2nm vs 66.4 ± 16.3 nm,P =0.000;Rq:202.2 ± 40.9nm vs 85.4 ± 17.1 nm,P =0.000).The adhesion force distribution was nearly three times higher in PBMCs of diabetic patients than that of the control group (779.6 ± 190.0pN vs 161.1 ± 83.1 pN,P =0.000).The Young's modulus of PBMCs was significantly increased in diabetic patients (421.4 ± 140.0kPa vs 138.3 ± 77.2kPa,P ＜ 0.01),indicating that diabetic PBMCs were stiffer than control cells.Conclusion Our study demonstrated the surface morphological and biomechanical properties changes in mitochondrial diabetes caused by mt.3243A ＞ G mutation at PBMCs level,which was beneficial to the better understanding of the pathophysiological mechanisms of mitochondrial diabetes associated with mt.3243A ＞ G mutation.

Mitochondrial diseases with the main manifestations of cardiomyopathy and respiratory muscle damage / 中华实用儿科临床杂志

Objective The 3243A ＞ G mutation in mitochondrial DNA is a common cause of the classical mitochondrial diseases characterized by neuro-muscular disorders.This study reports a rare case with the main manifestations of mitochondrial disease in children of mitochondrial cardiomyopathy and respiratory muscle damage.Methods The clinical characteristics,diagnosis and treatment,biochemical,pathological and genetic features of a 10-year-old girl were studied.Results The girl was admitted because of heart failure and respiratory failure at the age of 10.Ragged red fibers in skeletal muscles had been noticed.On her mitochondrial gene,3243A ＞ G mutation,Leu tRNA (UUR),was detected.The mutation rate in the peripheral blood cells was 94％.After the treatment with a high dose of creatine phosphate sodium,coenzyme Q10 and L-carnitine with assisted ventilation,the patient improved rapidly.The child was followed up for 2 years without recurrence.Meanwhile the growth,development and daily life were normal.Conclusions Cardiac and respiratory muscle impairments that appeared at the same time as the first manifestations of the children's mitochondrial disease is not common,and it is rare to have cardiomyopathy based mitochondrial gene 3243A ＞ G mutation is seldom seen clinically.Skeletal muscle biopsy and genetic test is the key for accurate diagnosis.Improving mitochondrial metabolism and assisted ventilation appear to be helpful treatments.