Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle.

N Bresolin; M Zeviani; E Bonilla; R H Miller; R W Leech; S Shanske; M Nakagawa; S DiMauro

doi:10.1212/wnl.35.6.802

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Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle.

N Bresolin·M Zeviani·E Bonilla·R H Miller·R W Leech·S Shanske·M Nakagawa·S DiMauro

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Abstract

A 2-month-old boy had progressive generalized weakness, hypotonia, and respiratory insufficiency requiring assisted ventilation. At age 3 1/2 months, he started having seizures and recurrent pulmonary infections; he died at age 7 months. Serum lactate was chronically elevated, but there was no aminoaciduria. Histochemical and ultrastructural studies of muscle biopsies at ages 2 and 3 months showed excessive mitochondria, lipid, and glycogen; a third biopsy at 6 months showed marked increase in perimysial fibrous and fat tissue. Cytochrome c oxidase activity was 7% of normal in the first biopsy and undetectable in the others. Cytochrome spectra of mitochondria isolated from postmortem muscle showed complete lack of cytochrome aa3. Antibodies were obtained against cytochrome c oxidase purified from normal human heart. Immunotitration and enzyme-linked immunosorbent assay (ELISA) showed decreased immunologically reactive enzyme protein in the patient's muscle, but SDS-PAGE electrophoresis of immunoprecipitates of muscle mitochondrial extracts showed the presence of all cytochrome c oxidase subunits. These data suggest that decreased synthesis of one or more subunits may result in markedly decreased concentration of electrophoretically normal complex IV in skeletal muscle.

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Cytochrome-c Oxidase Deficiency Electron Transport Complex IV Electrophoresis, Polyacrylamide Gel Humans Immunologic Techniques Infant Kidney Male Microscopy, Electron Mitochondria, Heart Mitochondria, Liver Mitochondria, Muscle Muscles Myocardium Case Reports Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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N Bresolin, M Zeviani, E Bonilla, R H Miller, R W Leech, S Shanske, M Nakagawa, S DiMauro. 1985. Fatal infantile cytochrome c oxidase deficiency: decrease of immunologically detectable enzyme in muscle.. https://doi.org/10.1212/wnl.35.6.802

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OBJECTIVE: To describe three patients with cytochrome c oxidase deficiency. DESIGN: Patient series. SETTING: Tertiary care children's hospital in Arkansas. PARTICIPANTS: A sibling pair and an unrelated patient referred for evaluation and found to have cytochrome c oxidase deficiency. INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Affected individuals had the characteristic presentation of psychomotor regression, growth deficiency, and lactic acidosis. The severity of the clinical course was found to correlate with the lactate-pyruvate ratio. Two of the infants had evidence, on magnetic resonance imaging, of subacute necrotizing encephalomyelopathy (Leigh disease). The most severely affected child had an unusual presentation of prenatal onset of structural anomalies including glabellar prominence, abnormal hair, loose skin, inguinal hernias, and hypospadias. CONCLUSIONS: The presentation and clinical course of cytochrome c oxidase deficiency are highly variable and the diagnosis of cytochrome c oxidase deficiency should be considered in all patients with lactic acidosis or subacute necrotizing encephalomyelopathy. Particular consideration should be given to this diagnosis when lactic acidosis is found in a neonate with structural anomalies.

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PubMed1992

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[A case of distal myopathy with rimmed vacuole formation, progresses into proximal-dominant muscle involvement].

A case of 55-year-old male with distal myopathy with rimmed vacuole formation is reported. He first noticed dragging of his legs at the age of forty-three. Two years later, he was evaluated to have muscle wasting and weakness in lower legs. In another ten years, he became unable to stand or walk unaided. On physical examination, proximal limb muscles were more severely affected than distal limb muscles. Notably, muscle strength of the quadriceps femoris muscles were weak (MRC Scale 3/5), compared to hamstrings, tibialis anterior muscle and gastrocnemius muscle (4/5). Serum creatine kinase, electromyography, nerve conduction velocities were all compatible with this diagnosis. A computed tomography of the musculoskeletal system was consistent with physical findings. Muscle biopsy revealed many fibers with typical rimmed vacuoles (approximately 6% of fibers). Additionally, small amount of ragged-red fibers (0.5%) was noted. Histochemical reaction showed a focal deficiency of cytochrome c oxidase. This case suggests that during the longstanding course of the illness, proximal limb muscles may be more severely affected, and quadriceps femoris muscle may be predominantly involved.

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