Clinical features of melas and mitochondrial DNA mutations

Goto, Yu‐ichi

doi:10.1002/mus.880181422

Cited by 87 publications

(62 citation statements)

References 30 publications

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“…However, the expression level was much lower than that in CPEO muscles. This study detected no apparent strongly SDH reactive blood (Goto 1995); consequently, no HNpositive vessels were observed.…”

Section: Expression Of Endogenous Hn In Cpeo Musclescontrasting

confidence: 43%

Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia

et al. 2006

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We showed that humanin (HN), an endogenous peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease. Because HN was recently found to block proapoptotic Bax function and exert its versatile cytoprotective effects in association with an increase in ATP levels, HN expression may thus reflect a physiological response against degenerative changes in the muscles of patients with CPEO. We found HN expression in all four patients examined, each of whom had different mitochondrial DNA mutations including two different single DNA deletions, multiple deletions, and no major mutations detected. We also found that HN expression was not linked to focal cytochrome c deficiency, strongly associated with the subtype of CPEO with single deletions. These results suggest that HN expression is more closely related to degenerative changes in all types of CPEO. Notably, HN was also expressed in non-degenerative muscle fibers of patients with CPEO or Leigh syndrome, who had the 8993T>G mutation in the mitochondrial ATPase 6 gene known to be associated with impaired ATP synthesis. Collectively, our findings suggest that HN may be specifically expressed in response to defects in energy production in muscles with mitochondrial abnormalities.

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Section: Expression Of Endogenous Hn In Cpeo Musclescontrasting

confidence: 43%

Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia

et al. 2006

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“…Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome typically manifests between the ages of five and 20 yr with variable phenotypic presentation and frequently progresses to severe multiorgan pathology and early death. 4,5 The disorder is characterized primarily by severe neurologic manifestations, including stroke-like episodes (confirmed by magnetic resonance imaging (MRI) as non-ischemic cerebral events not confined to a specific vascular territory), seizures, cognitive impairment, acute mental status changes (encephalopathy, psychosis), and migraines. 6 Commonly, patients have cardiac manifestations (preexcitation Wolff-Parkinson-White [WPW] syndrome, cardiac conduction pathway blockade, cardiomyopathy), diabetes mellitus, sensorineural hearing loss, gastrointestinal dysfunction, malnutrition, and muscle wasting.…”

Section: Résumémentioning

confidence: 99%

Considérations anesthésiques lors d’un syndrome d’encéphalomyopathie mitochondriale avec acidose lactique et épisodes ressemblant à des accidents vasculaires cérébraux: une série de cas

Gurrieri

Kivela

Bojanić

et al. 2011

Can J Anesth/J Can Anesth

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Purpose Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) is a rare inherited mitochondrial disorder associated with severe multiorgan pathology and stress-induced episodes of metabolic decompensation and lactic acidosis. The purpose of this case series is to review the medical records of patients with MELAS who underwent anesthetic care at the Mayo Clinic to observe their perioperative responses to anesthesia and to assess outcomes. Principal findings From September 1997 to October 2010, nine patients with MELAS were identified who underwent 20 general anesthetics, 12 prior to MELAS diagnosis. Debilitating neurologic symptoms involved eight patients, and three patients had substantial cardiac comorbidities. The patients tolerated commonly used anesthetics and muscle relaxants, including succinylcholine. Lactated Ringer's solution was used frequently. One patient was noted to have elevated postoperative serum lactate, but his serum lactate was chronically elevated. Metabolic acidosis was not observed in any patient. Hyponatremia and hyperkalemia, sometimes profound, were observed in seven patients, but these abnormalities also occurred at times remote from surgery. Two patients developed renal dysfunction following cardiac surgery and abdominal surgery for severe sepsis. Conclusion The MELAS patients developed episodes of hyponatremia and hyperkalemia of variable severity unrelated to the timing of surgery, suggesting these patients are prone to major electrolyte disturbances. Given the propensity to develop acid-base disturbances and lactacidemia, it is prudent to review and normalize electrolyte abnormalities and to adjust the anesthetic plan accordingly. Fortunately, the limited data suggest that patients with MELAS tolerate commonly used anesthetic drugs well. RésuméObjectif L'ence´phalomyopathie mitochondriale avec acidose lactique et e´pisodes ressemblant a`des accidents vasculaires ce´re´braux (MELAS) est un trouble mitochondrial he´re´ditaire rare associe´a`une pathologie grave touchant plusieurs organes et des e´pisodes de de´compensation me´tabolique et d'acidose lactique provoque´s par le stress. L'objectif de cette se´rie de cas est d'examiner les dossiers me´dicaux de patients atteints de MELAS et ayant reçu des soins anesthe´siques a`la Clinique Mayo afin d'observer leurs re´ponses pe´riope´ratoires a`l'anesthe´sie et d'e´valuer leurs devenirs. Constatations principales Pour la pe´riode allant de septembre 1997 a`octobre 2010, nous avons identifie´neuf patients atteints de MELAS ayant subi 20 anesthe´sies ge´ne´rales, dont 12 avant que le diagnostic de MELAS n'ait e´te´e´tabli. Les symptômes neurologiques de´bilitants ont touche´huit patients, et trois patients ont manifeste´des

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“…Later calcification may be seen in the basal ganglia and diffuse cerebral or cerebellar atrophy can occur 3,4,16,21 . The spreading mechanisms of stroke-like lesions also remain unknown, but may be due to vascular abnormalities resulting from mitochondrial angiopathy or a metabolic disorder caused by mitochondrial dysfunction-induced energy failure 5,7,9,14,16,21 . The RRF is the histological hallmark of proliferation of abnormal mitochondria in muscle fibers 1,22,23 .…”

Section: Fig 2 Muscle Biopsy: [A] Ragged-red Fibers On Modified Gomomentioning

confidence: 99%

“…Thus, recognition of subsarcolemmal accumulation of mitochondria without typical RRF in younger patients can be considered one minor histology criteria for mitochondrial disease diagnosis 23 . The accumulation of mitochondria in muscle fibers composing typical RRF has been found in up to 97% of MELAS patients 4,7,15 . In our group, more than 2% RRF were found in almost all patients but, as in other mitochondrial diseases, the SDH was a more sensitive marker of mitochondrial proliferation than the usual MGT stains 13 .…”

Section: Fig 2 Muscle Biopsy: [A] Ragged-red Fibers On Modified Gomomentioning

confidence: 99%

“…Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of occurring mitochondrial disease which includes in its definition encephalopathy, frequently with seizures and progressive dementia; stroke-like episodes at a young age; and biochemical evidence for mitochondrial defects, such as lactic acidosis or ragged-red fibers (RRF) in the muscle biopsy 3,4,6 . The pathogenesis of stroke-like episodes in MELAS is controversial; the two major hypotheses posit dependence on metabolic dysfunction or angiopathy in Melas Lorenzoni et al the brain, but these two elements are thought to be related 7 .…”

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23. MELAS: Clinical features, muscle biopsy and molecular genetics

Lorenzoni

Arndt

Freund

et al. 2009

Clinical Neurophysiology

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-Objective: The aim of the study was to analyze a series of Brazilian patients suffering from MELAS. Method: Ten patients with MELAS were studied with correlation between clinical findings, laboratorial data, electrophysiology, histochemical and molecular features. Results: Blood lactate was increased in eight patients. Brain image studies revealed a stroke-like pattern in all patients. Muscle biopsy showed ralled-red fibers (RRF) in 90% of patients on modified Gomori-trichrome and in 100% on succinate dehydrogenase stains. Cytochrome c oxidase stain analysis indicated deficient activity in one patient and subsarcolemmal accumulation in seven patients. Strongly succinate dehydrogenase-reactive blood vessels (SSV) occurred in six patients. The molecular analysis of tRNA Leu(UUR) gene by PCR/RLFP and direct sequencing showed the A3243G mutation on mtDNA in 4 patients. Conclusion: The muscle biopsy often confirmed the MELAS diagnosis by presence of RRF and SSV.

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Clinical features of melas and mitochondrial DNA mutations

Cited by 87 publications

References 30 publications

Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia

Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia

Considérations anesthésiques lors d’un syndrome d’encéphalomyopathie mitochondriale avec acidose lactique et épisodes ressemblant à des accidents vasculaires cérébraux: une série de cas

23. MELAS: Clinical features, muscle biopsy and molecular genetics

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