Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes with recurrent abdominal symptoms and coenzyme Q10 administration.

Abstract

SUMMARY A male with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes is reported. He had also recurrent episodes of ileus. Muscle biopsy revealed ragged-red fibres. The cytochemistry of cytochrome c oxidase (CCO) showed scattered nonstained fibres, while all muscle fibres were heavily stained by immunocytochemistry using CCO antibody. These findings suggest that partical CCO deficiency may be present in the skeletal muscles of the patient. NADH cytochrome c reductase in the patient's muscle mitochondria was low compared with normal controls (about 26%), although succinate cytochrome c reductase was normal. Coenzyme Q1O administration (90mg/day) did not improve CSF lactate levels, but did decrease plasma lactate levels. His muscle weakness slightly improved.Mitochondrial myopathy denotes a group of various disorders with mitochondrial abnormalities. In 1977, Shapira et al' noted a group of diseases characterised by central nervous system (CNS) symptoms, and advocated the term mitochondrial encephalomnyopathy, suggesting the presence of a common metabolic disorder in the muscle and CNS. Among patients with this disorder, Pavlakis et al2 described two of their own and nine in the literature showing mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS), and considered this condition to be a distinct clinical entity. We examined enzyme activity in the mitochondrial electron transport system in a patient with MELAS, and studied the effects of the administration of coenzyme Q0 (CoQO0), an important component of the system. Clinical features as well as the results of th-istreatment are reported.

Unusual occurrence of intestinal pseudo obstruction in a patient with maternally inherited diabetes and deafness (MIDD) and favorable outcome with coenzyme Q10

“…(17) reported the use of intravenous administration of Co Q10 in MELAS children who developed intestinal pseudo obstruction, resulting in gradual recovery in the following days. However, there are also reports of the occurrence of intestinal pseudo obstruction in patients already using Co Q10 (18,19,33). In our patient the introduction of Co Q10 as adjunctive therapy led to a resolution of the pseudo obstruction.…”

Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy.

“…Coenzyme Q has been hypothesized to stabilize the mitochondrial inner membrane by improving membrane fluidity, decreasing the effects of freeradical oxidation, and transferring electrons from complex I to III and from complex II to III (15)(16)(17). Treatment with high doses of coenzyme Q10 alone has been shown to have a therapeutic effect in KS/CEOP patients (18)(19)(20)(21)(22)(23) and in a MELAS patient (24,25).…”

Oxidative Phosphorylation Diseases

“…Commonly associated manifestations include dementia, generalized or focal seizure activity, chronic intermittent vomiting, deafness, migraine headaches, lactic acidosis, and short stature (Table I). Biochemical defects reported in MELAS include Complex I deficiency (lchiki et al, 1988;Hayes et al, 1985;Kobayashi et al, 1986Kobayashi et al, , 1987bPeterson et al, 1988;Sakuta and Nonaka, 1989) and a partial cytochrome c oxidase deficiency (M. Yamamoto et al, 1987;Shimoizumi et al, 1989). Abnormalities of phosphorylation potential have been reported in brain and skeletal muscle using 31 P-NMR (Hayes et al, 1985).…”

“…While most cases of MELAS are spontaneous occurrences within the pedigree (lchiki et al, 1988;Yoda et al, 1984;Kobayashi et al, 1982Kobayashi et al, , 1986Kobayashi et al, , 1987bGoda et al, 1987a,b;Hasuo et al, 1987;Mukoyama et al, 1986;Pavlakis et al, 1984;Bogousslavsky et al, 1982;Hayes et al, 1985;M. Yamamoto et al, 1987;Berkovic et al, 1987a), several informative pedigrees have characteristics that are compatible with an mtDNA mutation.…”

“…Early development is normal, with symptoms beginning in childhood (Hart et al, 1977;Montagna et al, 1988;Ichiki et al, 1988;Yoda et al, 1984;Kobayashi et al, 1986Kobayashi et al, , 1987bBogousslavsky et al, 1982; Pavlakis et al, 1984;Rowland, 1983), adolescence (Skoglund, 1979; M. Yamamoto et al, 1987;Goda et al, 1987a,b;Hasuo et al, 1987; Kobayashi et al, 1982;Hayes et al, 1985;Prick et al, 1983), or adulthood (Driscoll et al, 1987; T. Yamamoto et al, 1984;Ishitsu et al, 1987;Hasuo et al, 1987).…”