What is Mitochondrial Disease?

Mitochondrial disease is a group of heterogeneous lesions caused by genetic defects caused by defects in mitochondrial metabolic enzymes, resulting in impaired ATP synthesis and insufficient energy sources. Different types of mitochondrial encephalomyopathy have different ages.

Basic Information

English name: mitochondrial diseases
Visiting department: Internal medicine
Common locations: Skeletal muscle and central nervous system
Common causes: Disorders encoding enzymes or vectors necessary for mitochondrial oxidative metabolism

Common symptoms: Light activity is fatigue, accompanied by muscle soreness and tenderness; drooping eyelids, paralysis of extraocular muscles, eye movement disorders; neurological deafness and decreased intelligence

Causes of Mitochondrial Disease

Mitochondria are organelles that provide energy in cells. Human mtDNA is a 16569bp long double-stranded molecule divided into light and heavy chains. It contains 37 genes and mainly encodes respiratory chains and proteins related to energy metabolism. Deletion or point mutation of mtDNA makes the enzymes or vectors necessary for oxidative metabolism of mitochondria obstructed. Glycogen and fatty acids cannot enter the mitochondria to make full use of and produce sufficient ATP, resulting in energy metabolism disorders and complex clinical symptoms.

Clinical manifestations of mitochondrial disease

1. Mitochondrial myopathy usually starts at the age of 20, and is clinically characterized by skeletal muscles that are extremely intolerant of fatigue, mild activity and fatigue, often accompanied by muscle soreness and tenderness, and muscle atrophy is rare. Easily misdiagnosed as polymyositis, myasthenia gravis, and progressive muscular dystrophy.

2. Mitochondrial encephalomyopathy includes:

(1) Chronic progressive extraocular muscle paralysis (CPEO) usually starts in childhood. The first symptom is drooping eyelids, which slowly progresses to paralysis of all extraocular muscles, eye movement disorders, bilateral extraocular muscle symmetry, and diplopia. Common; some patients have pharyngeal and limb muscle weakness.

(2) Keams-Sayre Syndrome (KSS) started before the age of 20 and progressed rapidly, showing a triad: CPEO, retinal pigment degeneration, and cardiac block. Other neurological abnormalities include cerebellar ataxia, increased cerebrospinal fluid (CSF) protein, neurological deafness, and decreased intelligence.

(3) Mitochondrial encephalomyopathy with hyperlactic acidemia and stroke-like attack (MELAS) syndrome begins before the age of 40, and is more common in childhood. Sudden stroke-like episodes, such as hemiplegia, hemiplegia or cortical blindness, recurrent seizures, migraine, and vomiting, gradually worsen the condition.

(4) Myoclonic epilepsy with muscle fragmentation red fiber (MERRF) syndrome is most common in childhood, mainly manifesting myoclonic epilepsy, cerebellar ataxia, and weakness of the proximal limbs, which can be accompanied by multiple symmetry Lipoma.

Mitochondrial examination

(I) Laboratory inspection

Blood biochemical examination

(1) Blood lactic acid and pyruvate minimum exercise test: About 80% of patients did not return to normal after 10 minutes of exercise, and were positive; CSF lactic acid content also increased in patients with mitochondrial encephalomyopathy;

(2) Mitochondrial respiratory chain complex enzyme activity is reduced.

2.mtDNA analysis

(1) CPEO and KSS are deletions of mtDNA fragments, which may occur during egg or embryo formation;

(2) 80% of MELAS patients have 3243 point mutations in mtDNA and tRNA genes; MERRF syndrome has 8344 point mutations in tRNA gene loci.

(2) Other auxiliary inspections

1. Gomori staining biopsy of frozen muscle sections showed accumulation of mitochondria in muscle cells, increased RRF and glycogen fat.

2. CT or MRI examinations In patients with mitochondrial encephalomyopathy, white matter encephalopathy, calcification of the basal nucleus, brain softening, cerebral atrophy and enlarged ventricles can be seen.

3. EMG can be manifested as myogenic or neurogenic damage.

Diagnosis of mitochondrial disease

The diagnosis of mitochondrial myopathy depends on typical clinical symptoms: extreme inability to tolerate fatigue, short stature, and deafness in the proximal limbs, with clinical characteristics of each subtype; increased serum lactic acid, pyruvate, and muscle biopsy revealed RRF, The result of mtDNA deletion or point mutation. CT or MRI examination of patients with mitochondrial encephalomyopathy revealed white matter encephalopathy, calcification of the basal nucleus, brain softening, brain atrophy, and ventricular enlargement.

However, it should be noted that inflammatory myopathy and other myopathy may be accompanied by the possibility of mitochondria and glycogen accumulation. Prevent excessive and excessive diagnosis of mitochondrial myopathy.

Differential diagnosis of mitochondrial disease

Mitochondrial myopathy needs to be distinguished from polymyositis, myasthenia gravis, periodic paralysis, and progressive dystrophy of the eye-pharyngeal type.

Mitochondrial Disease Treatment

No specific treatment is currently available. Adenosine triphosphate (ATP), coenzyme Q10, and a large number of B vitamins can be given. Patients with pyruvate carboxylase deficiency are recommended a high protein, high carbohydrate, and low fat diet. Some cases respond well to adrenocortical hormones.

Mitochondrial disease prevention

The treatment of genetic diseases is difficult, and the curative effect is not satisfactory. Prevention is even more important. Preventive measures include the avoidance of marriage between close relatives, the introduction of genetic counselling, carrier genetic testing and prenatal diagnosis and selective abortion to prevent the birth of children.