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Hypertrophic cardiomyopathy with mitochondrial myopathy. A new phenotype of complex II defect
C Angelini1, P Melacini, M L Valente
1Neuromuscular Center, University of Padova, Italy.
Insights
This study identifies a novel mitochondrial disease in two brothers with hypertrophic cardiomyopathy. The research reveals a partial defect in complex II, a key component of cellular energy production.
Area of Science:
- Biochemistry
- Genetics
- Neuromuscular Disorders
Background:
- Hypertrophic cardiomyopathy (HCM) can present with diverse genetic underpinnings.
- Mitochondrial dysfunction is increasingly recognized as a contributor to various cardiomyopathies.
Observation:
- Two brothers presented with asymmetrical HCM and distinct limb-girdle muscle weakness.
- Electromyography (EMG) indicated a myopathic process, with elevated serum creatine phosphokinase (CPK) and aldolase levels.
- Muscle biopsies revealed "core-like" areas, subsarcolemmal mitochondrial accumulation, lipid deposits, and reduced succinate dehydrogenase activity.
Findings:
- Quantitative histochemical and biochemical analyses confirmed significantly reduced activity of succinate dehydrogenase and succinate-cytochrome C reductase, components of mitochondrial complex II.
- Myocardial biopsies showed lipid and mitochondrial abnormalities consistent with a mitochondriopathy.
- This constellation of findings represents a new phenotype of partial mitochondrial complex II defect.
Implications:
- This discovery expands the known spectrum of mitochondrial myopathies and cardiomyopathies.
- Understanding this partial complex II defect offers new diagnostic and therapeutic targets for related neuromuscular and cardiac conditions.
- Highlights the importance of investigating mitochondrial function in unexplained hypertrophic cardiomyopathy and muscle weakness.
Abstract:
Two brothers, 25 and 19 years old, were affected by asymmetrical hypertrophic cardiomyopathy. The older brother had waddling gait and weakness of the proximal girdle muscles, while the younger had a broad-based gait and weakness of selected limb girdle muscles. EMG exam was myopathic. Serum enzyme, CPK and aldolase were elevated. Histochemical reactions in muscle revealed "core-like" areas, subsarcolemmal rims of mitochondria and lipid accumulation. Succinate-dehydrogenase stain showed a lack of activity in both biopsies, with the exception of intrafusal fibers. Microphotometric quantitative measurements confirmed the defect in both biopsies. Biochemical measurements of several mitochondrial enzymes in muscle showed a reduced activity of succinate-dehydrogenase (33%) and succinate-cytochrome C reductase (36-47%) which are both components of complex II. On myocardial biopsy lipid and mitochondrial abnormalities were found. This mitochondriopathy represents a new phenotype of partial complex II defect.