Mitochondrial diseases in the narrow sense are caused only by abnormalities in mitochondrial DNA (mtDNA)

Broad mitochondrial disease can be caused by abnormalities in mitochondrial DNA or nuclear DNA (nDNA), or a combination of both.

such as tumor cells

The lesions are mainly in the central nervous system and are called mitochondrial encephalopathy

The disease is predominantly skeletal muscle and is called mitochondrial myopathy

Lesions involving both the central nervous system and skeletal muscles are called mitochondrial encephalomyopathy

Pyruvate dehydrogenase complex deficiency (PDHAD) (OMIM#312170)

Mohr-Tranebjaerg syndrome (MTS) (OMIM #304700), also known as dystonia-deafness syndrome

Mitochondrial complex II deficiency (OMIM#252011)

mtDNA multiple deletions

mtDNA depletion

First diagnosed human mitochondrial disease

The most significant clinical symptom of Leber optic atrophy is painless acute or subacute bilateral central vision loss caused by severe bilateral optic nerve atrophy. The visual acuity of both eyes may decrease simultaneously or successively.

In patients with LHON, the base at position 11778 of the ND4 subunit gene of the oxidative respiratory chain complex I (NADH dehydrogenase) was replaced from G to A (MTND4'LHON 11778A), resulting in a highly conserved DNA at position 340 of ND4. The amino acid is replaced by histidine, the spatial configuration of ND4 is changed, and the NADH dehydrogenase activity is reduced.

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The clinical manifestations are multi-system lesions, including myoclonic epilepsy, ataxia, myopathy, mental retardation, deafness, etc. In addition, the patient's muscle fibers are disordered and rough, and a large number of abnormally shaped mitochondria are often seen in the muscle cells, which are stained red with Gomori Trichrome and are called broken red fibers.

Clinical symptoms include abnormalities of the central system, including headaches, recurrent shock, epilepsy, stroke-like attacks, dementia, hemiplegia, cortical blindness, etc. Some patients may also be accompanied by clinical symptoms such as myopathy, vomiting, deafness, and short stature.

The main clinical symptoms are extraocular muscle palsy, retinitis pigmentosa, and cardiomyopathy. Patients also have symptoms such as limb weakness, cardiac conduction dysfunction, hearing loss, ataxia, and dementia.

Among them, about 1/3 of the patients are caused by the deletion of about 5 kb fragment between mtDNA8469~13447. The breakpoints of this deletion are located in the ATPase and ND5 genes respectively. The deletion results in the deletion of ATP8 ATP6, Cx3, ND3, ND4, ND4LND5 and multiple tRNA genes. The deleted region is flanked by 13 bases of direct repeat sequence (5'ACCTCCCTCACCA3')

An early-onset neurodegenerative disease caused by abnormal mitochondrial energy production. Clinical symptoms include elevated blood and/or cerebrospinal fluid lactate levels, symptoms of lesions in the brainstem and/or basal ganglia, hypotonia, spasticity, and hypotonia. Acute psychomotor retardation, hypotonia, ataxia, etc.

In Light syndrome caused by mtDNA mutations, the most common mutation is the T8993G or T8993C point mutation in the mtDNA AT6 gene. The mutation replaces leucine at position 156 of ATP 6 with arginine or proline, and the structure of ATP synthase occurs. Changes, the ATP synthesis activity of brain and retinal cells decreases, leading to cell death

There is a 4977bp DNA fragment deletion in the brain tissue of PD patients, especially in the substantia nigra. The breakpoints are located in the ATP8 gene and ND5 gene respectively. The deletion leads to functional defects in mitochondrial complexes I, II, III and even IV in various tissue cells. , which in turn causes energy metabolism disorders in neurons

Aging (OMIM #502000)

tumor

diabetes