Clinical And Genetic Analysis Of 7 Cases Of Mitochondrial Diseases

Objective Mitochondrial diseases are a group of genetic diseases characterized by the dysfunction of mitochondrial oxidative respiratory chain caused by the defects of mitochondrial genes or nuclear genes,which mainly involve brain and muscle tissue and contains a variet y of clinical subtypes.The clinical manifestations of mitoc hondrial diseases are complex and diverse,and there are obvious clinical and genetic heterogeneity between subtypes,which leads to difficulties in early clinical identification and high rates of misdiagnosis and mistreatment.This study summarizes and an al yzes the clinical and genetic mutation results of 7 patients with mitochondrial diseases admitted to our department in recent years.The aim is to summarize the clinical and genetic mutation characteristics of mitochondrial diseases,and to improve clinicians’ earl y recognition and diagnosis and treatment of the disease,and to reduce clinical misdiagnosis and mistreatment.Methods Retrospectively analyze and follow up the general data,clinical manifestations,laboratory and imaging examinations,muscle pathology and genetic testing data of seven patients with mitochondrial diseases admitted to the Department of Neurology,the General Hospital of Ningxia Medical Universit y from June 2013 to August 2020.Based on relevant literature,summarize the clinical and gene mutation characteristics of common and rare subt ypes of mitochondrial diseases.Results 1.In this study,all of 7 cases were clearly diagnosed by genetic testing,including three cases of mitochondrial encephalom yopathy with lactic acidemia and stroke-like episodes(MELAS),one case of Chronic progressive external ophthalmoplegia(CPEO),one case of Leigh s yndrome,one case of leukoencephalopathy with brain stem spinal cord involvement and lactate elevation(LBSL),one case of primary coenzyme Q10 deficiency syndrome.2.Cases 1-3 are patients with MELAS(2 males,age of onset 47 and 42 years;1 female,age of onset 44 years).The main clinical manifestations are stroke-like seizures,epileps y,headache,impaired exercise tolerance,and heari ng loss,Mental abnormalities,etc;brain MRI showed that the lace-like long T1,long T2,T2 FLAIR,and diffusion-weighted imaging(DWI)abnormal signals were mainly involved in the temporal parietal occipital cortex and subcortex;the genes test results showed a pathogenic mutation of mt DNAm.3243 A>G.3.Case 4 is a patient with CPEO,female,age 22 years old.The main clinical manifestations are chronic ptosis,eye movement disorders,impaired exercise tolerance,and headache;MRI of the brain shows deepe ning of bilateral sulcus fissures of the brain and cerebellum;electromyography The diagram and nerve conduction show peripheral nerve damage in the limbs;the genes test results showed a pathogenic mutation of mt DNAm.3243 A>G.4.Case 5 is a patient with Leigh s yndrome,male,age of onset 14 years old.The main clinical manifestations are recurrent seizures,headaches,nausea,and anorexia;brain MRI showed relativel y s ymmetrical long T1 and long T2 signals dominated by double basal ganglia putamen and cau date nucleus,and DWI showed High signal;the results of genetic testing showed a pathogenic mutation of chr M:13513.5.Case 6 is a patient with LBSL,female,age of onset 21 years old.The main clinical manifestation is progressive walking instability;MRI showed multiple symmetrical DWI high signals in bilateral medulla oblongata pyramidal tract,dorsolateral medulla oblongata,bilateral bridge arms,cerebellum and bilateral semi-oval centers.The results of genetic testing were compound heteroz ygous mutations in the DARS2 gene(c.228-16C>A and c.983A>G).6.Case 7 is a patient with primary coenzyme Q10 s yndrome,male,age of onset 12 years old.The main clinical manifestations are recurrent stroke-like seizures,epileps y,and headache;imaging shows repe ated high signal on DWI in different parts of the cortex with atrophy.The genetic test result was a homozygous mutation in the ADCK3 gene(c.637C>T,p.Arg213Trp).Conclusion 1.The main clinical manifestations of mitochondrial diseases are stroke-like attack,seizures,headaches,and decreased exercise tolerance.2.The imaging manifestations of mitochondrial diseases are diverse,and the lesions can progress,migrate or disappear with the development of the disease,the imaging features are resemble to acute ischemic lesions.3.Genetic testing is conducive to clarify the specific subtypes of mitochondrial diseases and their possible pathogenic mechanisms,and thus bring benefits to the treatment of patients.