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A mitochondrial encephalomyopathy with a partial cytochrome c oxidase deficiency of muscle
P M Van Erven1, F J Gabreëls, W Ruitenbeek
1Institute of Neurology, University Hospital Nijmegen, The Netherlands.
Insights
This study details a 16-year-old girl with probable Leigh syndrome, characterized by psychomotor delays and mitochondrial dysfunction. Muscle biopsies revealed ragged-red fibers and reduced cytochrome c oxidase activity, confirming impaired energy metabolism.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Pediatric Neurology
Background:
- Leigh syndrome is a severe, progressive neurodegenerative disorder affecting infants and children.
- It is primarily caused by genetic defects in mitochondrial energy metabolism.
- Early diagnosis and understanding of the underlying pathophysiology are crucial for management.
Observation:
- A 16-year-old female presented with delayed psychomotor development, exercise intolerance, and cerebellar signs.
- Progressive neurological deterioration, hypotonia, pyramidal and cerebellar syndrome, and epilepsy were noted from age 7.
- Cerebrospinal fluid (CSF) showed elevated pyruvate and lactate, with abnormal exercise and pyruvate loading tests.
Findings:
- Muscle biopsies revealed ragged-red fibers, decreased cytochrome c oxidase activity, and reduced cytochrome aa3 content.
- Fibroblast cytochrome c oxidase activity was normal, suggesting tissue-specific mitochondrial defects.
- Elevated CSF lactate and pyruvate, alongside muscle biopsy findings, indicated a disturbance in mitochondrial energy metabolism.
Implications:
- This case highlights the clinical and biochemical presentation of probable Leigh syndrome in an adolescent.
- The findings underscore the importance of investigating mitochondrial dysfunction in neurodegenerative disorders.
- Understanding tissue-specific mitochondrial defects can inform future diagnostic and therapeutic strategies for rare metabolic diseases.
Abstract:
A 16 year old girl showed delayed psychomotor development. In infancy, exercise intolerance, cerebellar signs, deteriorated with increasing intercurrent infections, and disturbances of breathing and cardiac rhythm became manifest. From the age of 7 years there was chronic progressive psychomotor deterioration, with hypotonia, a bilateral pyramidal and cerebellar syndrome, and mild epilepsy. CSF pyruvate and lactate levels were elevated, and lactate content was elevated in the urine. There was an abnormally high rise of lactate levels on moderate exercise and an abnormal response to pyruvate loading. Quadriceps muscle biopsies obtained at age 10 and 16 years showed ragged-red fibres, and a decreased cytochrome c oxidase activity and cytochrome aa3 content. Cytochrome c oxidase activity in fibroblasts was normal. Clinical signs and symptoms in association with a disturbance of mitochondrial energy metabolism led us to diagnosis of probable Leigh syndrome.