Myopathy mitochondrial

Metabolic Myopathies Glycogen Storage Disease Disorders of Lipid Metabolism Respiratory Chain Disorders Mitochondrial DNA Abnormalities Myotonias, Periodic Paralyses, and Malignant Hyperpyrexia Myotonias... 

The metabolic myopathies are exceptionally complex. Mitochondrial disorders are usually multisystem disorders, in which metabolic dysfunction affects muscle, liver, CNS, and special senses (especially vision) in almost any combination. There is evidence that some forms of mitochondrial disease are inherited, and the preponderance of maternal rather than paternal inheritance is consistent with an abnormality in the mitochondrial genome because almost all (and perhaps all) mitochondria are derived from the ovum. 

This complex consists of at least 25 separate polypeptides, seven of which are encoded by mtDNA. Its catalytic action is to transfer electrons from NADH to ubiquinone, thus replenishing NAD concentrations. Complex I deficiency has been described in myopathic syndromes, characterized by exercise intolerance and lactic acidemia. In at least some patients it has been demonstrated that the defect is tissue specific and a defect in nuclear DNA is assumed. Muscle biopsy findings in these patients are typical of those in many respiratory chain abnormalities. Instead of the even distribution of mitochondria seen in normal muscle fibers, mitochondria are seen in dense clusters, especially at the fiber periphery, giving rise to the ragged-red fiber (Figure 10). This appearance is a hallmark of many mitochondrial myopathies. 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

Human creatine kinase -MM MAK33 IgGl Cardiac disease, mitochondrial disorders, inflammatory myopathies, myasthenia, polymyositis, McArdle s disease, NMJ disorders, muscular dystrophy, ALS, hypo and hyperthyroid disorders, central core disease, acid maltase deficiency, myoglobinuria, rhabdomyolysis, motor neuron diseases, A. thaliana A. thaliana 2S2 seed storage protein SP + 0.02-0.4% TSP of fresh leaf extract (10-12% TSP of intercellular fluid) 52... 

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke like episodes (MELAS) Mitochondrial tRNA (leu)... 

Carnitine palmitoyltransferase deficiency is an autosomal recessive myopathy caused by a genetic defect of the mitochondrial enzyme CPT (Fig. 42-2). The disease is prevalent in men (male female ratio, 5.5 1) and appears to be the most common cause of recurrent myoglobinuria in adults [4]. 

HPPD hallucinogen persisting perception disorder MF.l.AS mitochondrial myopathy, encephalopathy, lactic... 

NING, C., KUHARA, T INOUE, Y, ZHANG, C.H., MATSUMOTO, M., SHINKA, T., FURUMOTO, T., YOKOTA, K., MATSUMOTO, I., Gas chromatographic mass spectrometric metabolic profiling of patients with fatal infantile mitochondrial myopathy with De Toni-Fanconi-Debre syndrome, Acta Paediatrica Japonica, 1996,38,661-666. 

Holt U, Harding AE, Morgan-Hughes JA. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 1988 331(6158) 717-719. 

Mitochondrial diseases are often expressed as neuropathies and myopathies because brain and muscle are highly dependent on oxidative phosphorylation. Mitochondrial genes code for some of the components of the electron transport chain and oxidative phosphorylation, as well as some mitochondrial tRNA molecules. 

Defects in mitochondrial proteins were first detected in muscle so that the term mitochondrial myopathy was used to describe these problems but, since they can arise in tissues other than muscle. 

Greg LeMond, who won the Tour de France cycle race three times, announced his retirement from competitive cycling in 1994 because of a mitochondrial myopathy . 

Chariot, P. et al. (1999) Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. Journal of Hepatology, 30 (1), 156-160. 

Phosphorus-31 MRS has been used widely to investigate mitochondria diseases in muscle. Trenell et al. measured an elevated ADP concentration and pHi in a group of mitochondrial myopathy (MM) patients, which is evidence of impaired oxidative ATP production in their skeletal mus-cle This study also showed that increased inspired oxygen concentration improves oxidative fimction in MM patients. In a separate study, Jeppesen et al. could not differentiate healthy subjects and MM patients using P MRS. ° They concluded the P MRS should not be a routine test in the diagnosis for MM patients. 

Muscle fibers from a patient with a mitochondrial myopathy show abnormal mitochondrial proliferation when stained for succinic dehydrogenase. 

Mitochondrial Myopathy. A general deticiency of iron may ho implicated in mitochondrial myopathy, which is a complex disorder that affects muscular activity. It lias been suspected for a number of years that the disorder is caused hy a delect of mitochondrial-protein transport. H.H.V. Sdiarpa and a team of researchers (Royal Free Hospital. London) postulate that a deficiency of an iron-sulfur protein in muscle dehydrogenase may be the specific cause. 

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