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Mitochondrial encephalomyopathies 

Mitochondrial encephalomyopathies

Mitochondrial encephalomyopathies

P F Chinnery

and D M Turnbull

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date: 29 April 2017

Mitochondrial encephalomyopathies are caused by primary defects in the respiratory chain that lead to disturbed generation of ATP by aerobic metabolism, which characteristically impairs the function of high-demand tissues such as the brain, eye, cardiac and skeletal muscle, as well as endocrine organs. The numerous proteins involved in this chain are encoded by genes in mitochondrial or nuclear DNA, mutations in many of which can lead to clinical disorders.

Clinical features

The clinical presentations of mitochondrial encephalomyopathies are highly variable: the same clinical syndrome can be caused by different genetic defects, and the same genetic defect may present in a variety of different ways. Several characteristic syndromes are described, including those produced by the following:

Large-scale single deletions of mitochondrial genome—typically cause progressive ophthalmoplegia and ptosis, and limb muscles may be affected; can also cause an extended phenotype of cerebellar ataxia, pigmentary retinopathy, sensorineural deafness, diabetes mellitus and heart block (Kearns–Sayre syndrome).

Pearson’s syndrome—pancreatic exocrine failure and hypoplastic bone marrow with sideroblastic anaemia in infancy; survivors may develop features of Kearns–Saye syndrome. Point mutations in the mitochondrial genome—may be present in adult life and are the major cause of visual loss in young adult males (Leber’s hereditary optic neuropathy). Other syndromes include Leigh’s syndrome—subacute necrotizing encephalomyopathy, with characteristic lesions in basal ganglia, cerebellum, and brainstem.

Nuclear genetic mutations with autosomal recessive inheritance—typically present in infants and children.

Investigation and treatment

Investigation—aside from general investigations to characterize the pattern and nature of organ involvement, the diagnostic strategy depends on the clinical context: (1) Inherited cases—in many patients it is possible to identify a specific clinical syndrome with a clear maternal family history suggestive of a mitochondrially inherited disorder. Under these circumstances it is appropriate (after counselling) to proceed directly to molecular genetic testing. (2) Sporadic cases—the key investigation is muscle biopsy for biochemical studies of oxidative phosphorylation, leading on to targeted molecular analysis of suitable samples of mitochondrial and nuclear DNA.

Treatment—there is no definitive treatment for patients with mitochondrial disease, except for those with deficiency of coenzyme Q10. Management is aimed at minimizing disability, preventing complications, and genetic counselling. Multidisciplinary expertise is needed to provide adequate nutrition and physiotherapy, and to address endocrinological, cardiac and ophthalmic complications.

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