الفهرس 
MitochondriaOnly 14 pages are availabe for public view
 |  | from | 164 |  |  |
| | | from | 164 | | |
Abstract
Mitochondria are spherical or filamentous granules 0.5-1 um wide that attain a length up to 10 um. They are primordial eukaryotic cells lacking the ability to use oxygen metabolically and colonized by intracellular aerobic bacteria. Mitochondria are composed of four compartments: Outer membrane, Inner membrane that composed predominantly of cardiolipin, Intermembrane space between outer & inner membranes and Matrix inside inner membrane (Aure et al., 2005).
Mutations are of two kinds; either microscopically detectable gross structural chromosomal changes or submicroscopic alterations involving one or a small number of nucleotides or what have been called point mutation (Mueller and Young, 1998).
Mutations in Mitochondrial DNA are associated with a variety of disorders for example, MELAS Syndromes (Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged red fibers), CPEO (chronic progressive external opthalmoplegia), Pearson’s syndrome and Kearns-Sayre syndrome (Zeviani et al., 1998).
The complexity of mitochondrial genetics and biochemistry are the reason of extremely heterogenous clinical manifestations of mtDNA disorders. They range from lesions of single tissues or structures, such as the optic nerve in Leber’s hereditary optic neuropathy (LHON), or the cochlea in maternally inherited non-syndromic deafness, to more widespread lesions including myopathies, encephalomyopathies, cardiopathies, or complex multisystem syndromes with onset ranging from neonatal to adult life (Zeviani and DiDonato, 2004).
However, typical ‘mitochondrial’ clues may be absent in some demonstrated mitochondrial disorders. This is the case for LHON, for neuropathy ataxia and retinitis pigmentosa (NARP), and it is also true in many paediatric cases of mitochondrial DNA disorders (Zeviani and DiDonato, 2004).
There is a broad spectrum of skin manifestations have been described with mitochondrial disorders as Hair abnormalities, pigmented skin lesions, rashes, hypertrichosis, acrocyanosis, pigmented alterations consistent with poikiloderma, vitiligo, hirsutism, petechae with cutis marmorata, anhydrosis, periorbital darkening and generalized hyperpigmentation associated with adrenal insufficiency (Bodemer et al., 1999) and (Maria et al., 2001).
The diagnosis of mitochondrial disorders relies upon clinical, biochemical and molecular genetic studies. The presence of a pattern of maternal inheritance should promt one to analyze mitochondrial DNA (mtDNA). The association of different apparently unrelated tissues can suggest the diagnosis (Wong et al., 2002).
It is important to emphasize that molecular investigation still fails to identify the responsible gene defect in 50% of adult patients affected by mitochondrial disease, as demonstrated by specific biochemical and/or morphological evidence. The percentage of undiagnosed cases increases to 80–90% for paediatric disorders (Zeviani and DiDonato, 2004).
Despite advances in our understanding of mitochondrial biochemistry and genetics, treatment options remain limited. The goals of treatment are to increase mitochondrial ATP production or efficiency of energy production, improve symptoms and halt progression of disease. The effectiveness of treatment varies with each patient (Gropman, 2001).