Multisystem manifestations of mitochondrial disorders

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J Neurol. 2009 Mar 1.

Multisystem manifestations of mitochondrial disorders.

Di Donato S.

Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano via Celoria 11, 20133,

Milan, Italy

Mitochondria are cytoplasmic organelles in eukaryotic cells that accomplish

several distinct vital functions, including oxidative phosphorylation, metabolic

anaplerotic and degradative pathways, and integration of signaling for

apoptosis. Impaired oxidative phosphorylation, the common final pathway of

mitochondrial metabolism, results in a variety of clinical manifestations, and

the term mitochondrial disorders is currently ascribed to (mostly) genetic

diseases of the respiratory chain associated with mitochondrial DNA mutation or

nuclear DNA mutations.

Genetic disorders with impaired oxidative phosphorylation are extremely

heterogeneous, as their clinical presentation ranges from lesions of single

tissues or specialized structures, such as the optic nerve in the mitochondrial

DNA-associated Leber's hereditary optic neuropathy and in the nuclear

DNA-associated dominant optic atrophy, to more widespread pathologies, including

myopathies, peripheral neuropathies, encephalomyopathies, cardiopathies, or

complex multisystem disorders.

The age at onset ranges from neonatal to adult life. This review focuses on

mitochondrial diseases that find significant expression outside the central

nervous system and the peripheral neuromuscular system, and manifest with

substantial clinical signs and symptoms in tissues and organs such as the heart,

endocrine system, liver, kidney, blood, and gastrointestinal tract. The

available information on putative genotype-phenotype correlations and the

related pathogenic mechanisms are summarized when appropriate.