Fatal infhntile mitochondrial myopathy and renal dysfunction due to cytochrome‐c‐oxidase deficiency

DiMauro, Salvatore; Mendell, Jerry R.; Sahenk, Zarife; Bachman, David; Scarpa, Antonio; Scofield, Richard M.; Reiner, Charles B.

doi:10.1212/wnl.30.8.795

Cited by 196 publications

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“…Rarer still is the symptom onset in adults with no preceding respiratory symptoms, as in our patient. Most cases of COX deficiency are detected in infancy [4,5], though there have been case reports in older children [6]. Presentation during adulthood has been previously reported [7][8][9][10][11], usually with either preceding lifelong respiratory symptoms or other chronic symptoms.…”

Section: Discussionmentioning

confidence: 99%

A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency

O'Brien¹,

Blaivas²,

Albers³

et al. 1998

Eur Respir J

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aaCytochrome c oxidase (COX) is a complex mitochondrial enzyme involved in oxidative phosphorylation. COX deficiency can result in a myopathy. We describe a patient with acute respiratory failure and pulmonary hypertension secondary to a partial COX enzyme deficiency. This is one of four reported cases with isolated late-onset COX deficiency involving muscle, sparing ocular or central nervous system function. This patient also illustrates the need to consider neuromuscular weakness in the differential diagnosis of dyspnoea, respiratory failure and pulmonary hypertension. Finally, the effectiveness of bilevel positive airway pressure (BiPAP) therapy in respiratory failure due to a myopathy is demonstrated. Case reportA 27 yr old woman was admitted to another hospital after 3 months of progressive dyspnoea on exertion. She was short of breath on walking up <1 flight of stairs. She also complained of coughing and some wheezing. Previous treatment included numerous courses of antibiotics and systemic corticosteroids without benefit. The patient had no prior illnesses; she was on no other medications, and had no known environmental exposures. She had never smoked cigarettes or abused alcohol or drugs. Her family history was noncontributory.Physical examination revealed the blood pressure to be 127/64 mmHg, heart rate 98 beats·min -1 , respiratory rate 23 breathes·min -1 . The patient was afebrile and in mild respiratory distress. There was evidence of pulmonary hypertension. A chest examination revealed limited thoracic movement and diminished breath sounds without wheezing or crackles. The patient had 3+ peripheral oedema. The neuromuscular exam was normal, including eye movements. Initial arterial blood gas analysis on room air: pH 7.36, O 2 tension in arterial blood (Pa,O 2 ) 4.1 kPa (31 mmHg), CO 2 tension in arterial blood (Pa,CO 2 ) 9.4 kPa (71 mmHg). The routine laboratory evaluation was unremarkable. The chest radiograph revealed cardiomegaly with central pulmonary vascular engorgement. Supplemental oxygen was administered, and the Pa,O 2 rose to 9.0 kPa (68 mmHg); however, the Pa,CO 2 progressively rose, ultimately requiring ventilatory support. Evaluation of the pulmonary hypertension included the following: cardiac ultrasound showed marked right atrial and ventricular enlargement, with moderate tricuspid regurgitation and normal left ventricular function. There was no evidence of intracardiac shunts. The ventilation-perfusion lung scan and lower extremity duplex ultrasound were normal. Right heart catheterization revealed a pulmonary artery pressure of 97/52 mmHg, cardiac output/index 7/3.5 L·min -1 , pulmonary capillary wedge pressure 18 mmHg, central venous pressure 27 mmHg, systemic vascular resistance 881 dyne·s -1 ·cm -5 , pulmonary vascular resistance 576 dyne·s -1 ·cm -5 . The patient was successfully extubated 2 days later and transferred to our hospital.Further evaluation at our hospital included: arterial blood gases, which showed pH 7.27, Pa,O 2 11.0 kPa (83 mmHg), Pa,CO 2 10.5 kPa (79 mmHg) on ...

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Section: Discussionmentioning

confidence: 99%

A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency

O'Brien¹,

Blaivas²,

Albers³

et al. 1998

Eur Respir J

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“…[6][7][8][9] We measured the activities of cytochrome c oxidase (COX, complex IV), succinate-cytochrome c reductase (complexes II and III), NADH-cytochrome c reductase (complexes I and III), NADH-dehydrogenase (complex I), succinate dehydrogenase (SDH, complex II), and citrate synthase (a matrix enzyme) in liver extracts.…”

Section: Biochemistry and Histochemistrymentioning

confidence: 99%

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Tanji

Holve

et al. 2001

Hepatology

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“…Cases have been reported in which the activities of complex I (3), complex III (4,5), and complex IV (6) are greatly diminished or, in some cases, completely absent.…”

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confidence: 99%

Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis.

Darley‐Usmar¹,

Kennaway²,

Buist³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

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The skeletal muscle of a patient with a mitochondrial myopathy was examined. A defect in the electron transport chain was identified at the position of complex m by activity measurements and the low levels of reducible cytochrome b. The polypeptide composition of complex Ill in the patient's mitochondria was determined by antibody binding experiments. The method allowed detection of individual polypeptides at a lower limit of 10-40 ng of protein. Characterization of protein composition is thus possible by using a biopsy sample of 1 g of tissue. The level of core proteins, FeS protein, and subunit VI was greatly diminished in the patient's mitochondria. Cytochrome cl polypeptide was found at normal levels but was sensitive to proteolysis by trypsin. These results show that complex III is not assembled in the patient's mitochondria. The possible role of cytochrome b as the site of the primary lesion is discussed.

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Fatal infhntile mitochondrial myopathy and renal dysfunction due to cytochrome‐c‐oxidase deficiency

Cited by 196 publications

References 0 publications

A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency

A case of respiratory muscle weakness due to cytochrome c oxidase enzyme deficiency

Navajo Neurohepatopathy: A Mitochondrial Dna Depletion Syndrome?

Deficiency in ubiquinone cytochrome c reductase in a patient with mitochondrial myopathy and lactic acidosis.

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