Mitochondrial encephalomyopathies

S. DiMauro and C. T. Moraes
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, College of Physicians and Surgeons, Columbia University, New York, NY.

Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of "mitochondrial genetics," including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Brain Magnetic Resonance Imaging Findings in Patients With Mitochondrial Cytopathies
Barragan-Campos et al.
Arch Neurol 2005;62:737-742.
ABSTRACT | FULL TEXT  

Prevalence of large-scale mitochondrial DNA deletions in an adult Finnish population
Remes et al.
Neurology 2005;64:976-981.
ABSTRACT | FULL TEXT  

Evaluation of cytogenetic and DNA damage in mitochondrial disease patients: effects of coenzyme Q10 therapy
Migliore et al.
Mutagenesis 2004;19:43-49.
ABSTRACT | FULL TEXT  

Mitochondrial Myopathy in a German Shepherd Dog
Paciello et al.
Vet Pathol 2003;40:507-511.
ABSTRACT | FULL TEXT  

Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome
Bosbach et al.
Brain 2003;126:1231-1240.
ABSTRACT | FULL TEXT  

Proton MR Spectroscopy in the Diagnostic Evaluation of Suspected Mitochondrial Disease
Lin et al.
Am. J. Neuroradiol. 2003;24:33-41.
ABSTRACT | FULL TEXT  

Distal myopathy with tubular aggregates: a new phenotype associated with multiple deletions in mitochondrial DNA?
Garrard et al.
J. Neurol. Neurosurg. Psychiatry 2002;73:207-208.
FULL TEXT  

Reduced oxidative phosphorylation and proton efflux suggest reduced capillary blood supply in skeletal muscle of patients with dermatomyositis and polymyositis: a quantitative 31P-magnetic resonance spectroscopy and MRI study
Cea et al.
Brain 2002;125:1635-1645.
ABSTRACT | FULL TEXT  

Mitochondrial Encephalomyopathy: Comparison of Conventional MR Imaging with Diffusion-Weighted and Diffusion Tensor Imaging: Case Report
Majoie et al.
Am. J. Neuroradiol. 2002;23:813-816.
ABSTRACT | FULL TEXT  

mtDNA Disease in the Primary Care Setting
Spellberg et al.
Arch Intern Med 2001;161:2497-2500.
ABSTRACT | FULL TEXT  

Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family
Rantamaki et al.
Neurology 2001;57:1043-1049.
ABSTRACT | FULL TEXT  

Mutation analysis of the entire mitochondrial genome using denaturing high performance liquid chromatography
van den Bosch et al.
Nucleic Acids Res 2000;28:e89-e89.
ABSTRACT | FULL TEXT  

Cerebral blood flow and glucose metabolism in mitochondrial disorders
Molnar et al.
Neurology 2000;55:544-548.
ABSTRACT | FULL TEXT  

Mitochondrial Respiratory-Chain Defects Presenting as Nonspecific Features in Children
Tsao et al.
J Child Neurol 2000;15:445-448.
ABSTRACT  

Neurologic Presentations of Mitochondrial Disorders
Nissenkorn et al.
J Child Neurol 2000;15:44-48.
ABSTRACT  

Threshold Effect and Tissue Specificity. IMPLICATION FOR MITOCHONDRIAL CYTOPATHIES
Rossignol et al.
J. Biol. Chem. 1999;274:33426-33432.
ABSTRACT | FULL TEXT  

Multiple presentation of mitochondrial disorders
Nissenkorn et al.
Arch. Dis. Child. 1999;81:209-214.
ABSTRACT | FULL TEXT  

Congenital Hydranencephalic-Hydrocephalic Syndrome Associated With Mitochondrial Dysfunction
Castro-Gago et al.
J Child Neurol 1999;14:131-135.
ABSTRACT  

A Case of Late-Onset MELAS
Kimata et al.
Arch Neurol 1998;55:722-725.
ABSTRACT | FULL TEXT  

Mitochondrial myopathy with atypical subacute presentation
COHEN et al.
J. Neurol. Neurosurg. Psychiatry 1998;64:410-411.
FULL TEXT  

Mitochondrial Encephalomyopathy and Hypoparathyrodism Associated with a Duplication and a Deletion of Mitochondrial Deoxyribonucleic Acid
Tengan et al.
J. Clin. Endocrinol. Metab. 1998;83:125-129.
ABSTRACT | FULL TEXT  

Clinical features, investigation, and management of patients with defects of mitochondrial DNA
CHINNERY and TURNBULL
J. Neurol. Neurosurg. Psychiatry 1997;63:559-563.
FULL TEXT  

Direct detection of multiple point mutations in mitochondrial DNA
Wong and Senadheera
Clin. Chem. 1997;43:1857-1861.
ABSTRACT | FULL TEXT  

Biochemical and Molecular Consequences of Massive Mitochondrial Gene Loss in Different Tissues of a Mutant Strain of Drosophila subobscura
Beziat et al.
J. Biol. Chem. 1997;272:22583-22590.
ABSTRACT | FULL TEXT  

Cardiomyopathies in disorders of oxidative metabolism
Antozzi and Zeviani
Cardiovasc Res 1997;35:184-199.
ABSTRACT | FULL TEXT  

In vivo functional investigations of lactic acid in patients with respiratory chain disorders
Touati et al.
Arch. Dis. Child. 1997;76:16-21.
ABSTRACT | FULL TEXT  

Topical Review: Antidyskinetic Drug Therapy for Pediatric Movement Disorders
Pranzatelli
J Child Neurol 1996;11:355-369.
ABSTRACT  

Leber's Congenital Amaurosis Associated With Mitochondrial Dysfunction
Castro-Gago et al.
J Child Neurol 1996;11:108-111.
ABSTRACT  

Functional and Molecular Mitochondrial Abnormalities Associated with a C [IMAGE] T Transition at Position 3256 of the Human Mitochondrial Genome
Hao and Moraes
J. Biol. Chem. 1996;271:2347-2352.
ABSTRACT | FULL TEXT  

Mitochondrial DNA and Disease
Johns
NEJM 1995;333:638-644.
FULL TEXT  

Intracellular Localization of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria
Kang et al.
J. Biol. Chem. 1995;270:14659-14665.
ABSTRACT | FULL TEXT