Mitochondrial myopathy with skeletal muscle cytochrome oxidase deficiency

Lactic Acidosis and Mitochondrial Myopathy Associated with Deficiency of Several Components of Complex III of the Respiratory Chain

“…The absence of hypoglycemia and central nervous system signs reduced the likelihood of a defect of pyruvate carboxylase or the pyruvate dehydrogenase complex. However, the association of lactic acidosis with muscle weakness and the appearance of a typical ragged red fiber myopathy has been reported in several patients believed to have a disorder of the respiratory chain including NADH-coenzyme Q reductase deficiency (25,26,32,33,40), cytochrome b deficiency (3 1,33,42), and cytochrome c oxidase deficiency (14,15,43,47,49). With the exception of cytochrome oxidase, most of these deficiencies have been deduced from spectral or oxygen consumption studies alone.…”

“…In several of the mitochondrial deficiencies, tissues other than skeletal muscle may be involved. Examples are the cardiomyopathy associated with muscle carnitine deficiency (21), or the renal Fanconi syndrome described in several patients with cytochrome c oxidase deficiency (14,43,47). Involvement of the CNS also occurs in many of these conditions and may cause overwhelming clinical disease.…”

“…Patients with less severe defects of this system have a much milder phenotype with intermittent ataxia and minimal lactic acidosis (23). Severe lactic acidosis is frequent in patients with pyruvate carboxylase deficiency (2,22,39,48) and mild to severe lactic acidosis is found in defects of the respiratory chain (14,25,26,(31)(32)(33)40,43,47,49).…”

“…The sites of these defects have generally been identified by studies of oxygen consumption in the presence of various substrates or by spectral analysis of the cytochromes. More recently, measurements of enzyme activities have helped to localize the sites of these deficiencies (14,26,33,43,47,49). However, in no case were the individual polypeptides of complexes I-IV examined, so that the primary lesion in these patients is not known.…”

Oxidative Phosphorylation Diseases

“…In 19 biochemically characterized cases which fit our definition of LIMD, the mean age of onset was 3 weeks, with death occurring on the average at 5 months and associated with overwhelming lactic acidosis Rimoldi et al, 1982;Sengers et al, 1984;Bresolin et al, 1985;DiMauro et al , 1980;Heiman-Patterson et al, 1982;Moreadith et al , 1984Moreadith et al , , 1987Boustany et al , 1983;Aprille, 1985;Van Biervliet et al, 1977;Stansbie et al, 1982;Minchom et al, 1983;Muller-Hocker et al, 1983;Trijbels et al , 1983;Robinson et al, 1985Robinson et al, , 1986Zheng et al, 1989). While the clinical course was similar in all cases, only a few patients had a multiorgan pathological or biochemical assessment which could evaluate the extent of tissue dysfunction.…”