Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029089 (ophthalmoplegia)
 3,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies.
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PMID:Inherited mitochondrial neuropathies. 2140 91

There has been considerable progress during the past 24 years in the molecular genetics of mitochondrial DNA and related nuclear DNA mutations, and more than 100 nerve biopsies from hereditary neuropathies related to mitochondrial cytopathy have been accurately examined. Neuropathies were first reported in diseases related to point mutations of mitochondrial DNA, but they proved to be a prominent feature of the phenotype in mitochondrial disorders caused by defects in nuclear DNA, particularly in 3 genes: polymerase gamma 1 (POLG1), mitofusin 2 (MFN2), and ganglioside-induced differentiation-associated protein 1 (GDAP1). Most patients have sensory-motor neuropathy, sometimes associated with ophthalmoplegia, ataxia, seizures, parkinsonism, myopathy, or visceral disorders. Some cases are caused by consanguinity, but most are sporadic with various phenotypes mimicking a wide range of other etiologies. Histochemistry on muscle biopsy, as well as identification of crystalloid inclusions at electron microscopy, may provide a diagnostic clue to mitochondriopathy, but nerve biopsy is often less informative. Nevertheless, enlarged mitochondria containing distorted or amputated cristae are highly suggestive, particularly when located in the Schwann cell cytoplasm. Also noticeable are clusters of regenerating myelinated fibers surrounded by concentric Schwann cell processes, and such onion bulb-like formations are frequently observed in neuropathies caused by GDAP1 mutations.
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PMID:Mitochondria and peripheral neuropathies. 2314 4