Mitochondrial diseases are a group of heterogeneous diseases with ATP synthesis disorder caused by gene defects and insufficient energy sources. Different types of mitochondrial encephalomyopathy have different onset ages. Mitochondria are organelles closely related to energy metabolism. Cell survival (oxidative phosphorylation) and cell death (apoptosis) are related to mitochondrial function, especially abnormal oxidative phosphorylation of respiratory chain is related to many human diseases. According to the location of mitochondrial lesions, it can be divided into: 1. Mitochondrial myopathy Mitochondrial lesions mainly invade skeletal muscle. 2. Mitochondrial encephalomyopathy invades skeletal muscle and central nervous system.
Symptoms and signs
? 1. Mitochondrial myopathy: Most patients begin at the age of 20, some children and middle-aged people, and both men and women are involved. The clinical feature is that skeletal muscle is extremely intolerant to fatigue, and feels tired after mild activity, often accompanied by muscle soreness and tenderness, and muscular atrophy is rare, which is easily misdiagnosed as polymyositis, myasthenia gravis and progressive muscular dystrophy.
2.？ Mitochondrial encephalomyopathy includes:
(1) Chronic progressive extraocular muscle paralysis (CPEO): It generally begins in childhood, with drooping eyelids as the first symptom, and then gradually develops into complete extraocular muscle paralysis, eye movement disorder, bilateral extraocular muscles are symmetrically involved, and diplopia is uncommon; Some patients have myasthenia of pharyngeal muscles and limbs.
(2) Keams-Sayre syndrome (KSS): onset before the age of 20, rapid progress, CPEO and retinitis pigmentosa, often accompanied by heart block, cerebellar ataxia, increased cerebrospinal fluid protein, nervous deafness and mental retardation.
(3) Mitochondrial encephalomyopathy with Hyperlactic Acid and Stroke-like Attack (MELAS) Syndrome: onset before the age of 40, with more childhood attacks, manifested as sudden stroke-like attacks, such as hemiplegia, hemianopia or cortical blindness, recurrent attacks, migraine and vomiting, and the condition worsened. CT and MRI can show the softening of occipital lobe, and the focus range is inconsistent with the distribution of cerebral vascular trunk, such as brain atrophy, ventricular enlargement and calcification of basal ganglia. Blood and cerebrospinal fluid lactic acid increased.
(4) Myoclonic epilepsy with muscle hair red fiber (MERRF) syndrome: it is common in childhood, mainly manifested as myoclonic epilepsy, cerebellar ataxia and proximal limb weakness, and may be accompanied by multiple symmetric lipomas.
3.？ Mitochondrial encephalopathy: including Lieber's hereditary optic neuropathy (LHON), subacute necrotizing encephalomyelitis (Lee's disease), Albers disease and Menkes's disease.
Mitochondrial diseases usually occur in infants, children or early adults, and the course of disease is progressive or progressive. The common manifestations of infants are stillbirth or stillbirth, progressive encephalopathy, myasthenia, epilepsy, growth retardation and so on. The common manifestations of adults include binocular vision loss, stroke-like seizures in young people, myoclonic epilepsy, myasthenia, ptosis and diplopia, diabetes, gastrointestinal diseases and so on. Diseases caused by mtDNA mutation are generally maternal inheritance, that is, patients can only get defective mtDNA from their mothers, and male patients will never have sick children.
However, because the incidence of mitochondrial diseases is affected by the proportion of mtDNA mutations in vivo and the emergence of new mutations, a considerable number of patients do not have a clear maternal family history. However, respiratory chain defects caused by nuclear gene mutations conform to autosomal dominant, recessive or sporadic patterns. Some neurodegenerative diseases have also been proved to be related to respiratory chain defects, such as Parkinson's syndrome and amyotrophic lateral sclerosis.