Disease Overview Mitochondrial diseases can be caused by either nuclear or mitochondrial gene defects, and thus these diseases can have multiple modes of inheritance, such as matrilineal, Mendelian, or both. First, mitochondrial disease phenotypes are diverse and can overlap with each other. The same mtDNA mutation can produce different phenotypes, and different mtDNA mutations can produce similar phenotypes. Second, except for a few mitochondrial diseases that affect only a single organ, the vast majority can affect multiple organ systems. The mitochondrial respiratory chain is the necessary and ultimate pathway for aerobic metabolism, and thus tissues and organs that depend on aerobic metabolism, such as the heart, brain, and muscles, are often the first to be affected and have prominent symptoms. Third, mitochondrial disease can occur at any age. In general, those with nDNA abnormalities develop in early childhood, while those with mtDNA abnormalities develop in childhood and later adulthood. Fourth, many patients present with a range of clinical symptoms that belong to a discrete group of clinical signs. Common clinical manifestations include ptosis, external ophthalmoplegia, proximal myopathy, motor intolerance, cardiomyopathy, sensorineural deafness, optic nerve atrophy, retinitis pigmentosa, diabetes mellitus, spasticity or convulsions, dementia, migraine, stroke-like episodes, chorea, and dementia. Fifth, in many cases a maternal history can be strongly suggestive of mitochondrial disease. The human mtDNA is a 16,569 bp long circular double-stranded molecule, divided into light and heavy strands, containing 37 genes, encoding mainly respiratory strands and proteins related to energy metabolism. mtDNA deletion or point mutation causes disruption of enzymes or carriers that encode for the mitochondrial oxidative hyperaemia process, preventing glycogen and fatty acids from entering the straight mitochondria to fully utilize and This results in impaired energy metabolism and complex clinical symptoms. Mitochondrial disease is a matrilineal mode of inheritance that differs from Mendelian inheritance because the mitochondria of the fertilized egg are derived from the ovum. It is similar to autosomal disorders, but more individuals develop each generation than autosomal disorders. Mothers pass mtDNA to their offspring, and only daughters can pass mtDNA to the next generation. Because the relative proportion of mtDNA per cell is relevant, patients will only develop symptoms when the mutant phenotype reaches a certain threshold. Symptoms Mitochondrial diseases are a heterogeneous group of lesions caused by genetic defects that cause defects in mitochondrial metabolic enzymes, resulting in impaired ATP synthesis and inadequate energy sources. luft et al. (1962) first reported a case of mitochondrial myopathy, which was biochemically and severely confirmed to be caused by oxidative phosphorylation decoupling. anderson (1981) determined the full-length sequence of human mitochondrial DNA (mtDNA), and Holt ( 1988) found mtDNA deletion for the first time in patients with mitochondrial disease, confirming that mtDNA mutations are an important cause of human disease and establishing a new concept of mitochondrial inheritance that is different from Mendelian inheritance. Mitochondrial lesions can be classified according to their location: (1) mitochondrial myopathy: mitochondrial lesions invade mainly skeletal muscle; (2) mitochondrial encephalomyopathy: lesions invade both skeletal muscle and the central nervous system; (3) mitochondrial encephalopathy: lesions invade mainly the central nervous system. Diagnosis (a) auxiliary tests: 1, blood biochemistry check ① blood lactate, pyruvate minimum exercise test: about 80% of patients with exercise 10 minutes after the blood lactate and pyruvate still can not return to normal, is positive; mitochondrial encephalomyopathy patients CSF lactate content is also increased; ② mitochondrial respiratory chain complex enzyme activity is reduced. 2, muscle frozen section Gomori staining biopsy can be seen intra-myocyte mitochondrial accumulation, RF and glycogen fat increase. 3, CT or MRI examination: white matter encephalopathy, basal ganglia calcification, brain softening, brain atrophy and ventricular enlargement are seen in patients with mitochondrial encephalomyopathy. 4.Electromyography: it can be myogenic damage or neurogenic damage. 5.mtDNA analysis ①CPEO and KSS are mtDNA fragment deletion, which may occur in the egg or embryo formation stage; ②80% of MELAS patients are mtDNA tRNA gene 3243 point mutation; MERRF syndrome is tRNA gene locus 8344 point mutation. (B) diagnosis and differential diagnosis 1, diagnosis: based on extreme intolerable fatigue of the proximal extremities, physical dwarfism and neurogenic deafness, accompanied by clinical features of each subtype; increased blood lactate and pyruvate, muscle biopsy found RRF, mtDNA deletion or point mutation, etc. 2, differential diagnosis: need to opinion on polymyositis, myasthenia gravis, periodic paralysis and oculopharyngeal progressive myotonic dystrophy, etc. to differentiate. Treatment There is no specific treatment. ATP, coenzyme Q10 and large amounts of B vitamins can be given. A high protein, high carbohydrate and low fat diet is recommended for patients with pyruvate carboxylase deficiency. Complications 1. Mitochondrial myopathy: mostly starts at the age of 20, but also in children and middle age, both men and women are affected. The clinical features are extreme fatigue intolerance of skeletal muscles, fatigue with light activity, often accompanied by muscle pain and pressure pain, myasthenia gravis is rare. It is easily misdiagnosed as polymyositis, myasthenia gravis and progressive myotonic dystrophy. Mitochondrial encephalomyopathy includes: (1) Chronic progressive extraocular muscle paralysis (CPEO): the first symptom is eyelid ptosis, slowly progressing to total extraocular muscle paralysis, eye movement disorders, bilateral extraocular muscle symmetrical involvement, diplopia is uncommon; some patients have pharyngeal muscle and limb muscle weakness. (2) Kearns-Sayre syndrome (KSS): the disease starts before 20 years of age and progresses rapidly, showing CPEO and retinitis pigmentosa, often accompanied by heart block, cerebellar ataxia, increased CSF protein, neurogenic deafness and mental retardation. (3) Mitochondrial encephalomyopathy with hyperlactatemia and stroke-like episodes (MELAS) syndrome: The disease starts before the age of 40 years, with more frequent onset in childhood. CT and MRI show cerebral softening in the occipital lobe, with lesions that do not correspond to the distribution of the major cerebral vessels, and cerebral atrophy, ventricular enlargement, and calcification of the basal ganglia. (4) Myoclonic epilepsy with muscle fluffy red fibers (MERRF) syndrome: mostly in childhood, mainly manifesting myoclonic epilepsy, cerebellar ataxia and proximal weakness of the limbs, etc. It can be accompanied by multi-issue symmetric lipoma. Mitochondrial encephalopathies include Leer hereditary optic neuropathy (LHOW), subacute necrotizing encephalomyelopathy (Leigh disease), Alpers disease and Menkes disease.