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Muscle involvement in pyruvate dehydrogenase complex (PDHC) deficiency
Insights
Pyruvate dehydrogenase complex deficiency causes severe neurological and developmental issues in infants. This study details muscle biopsy findings in two young patients with this rare metabolic disorder.
Area of Science:
- Biochemistry
- Neurology
- Genetics
Background:
- Pyruvate dehydrogenase complex (PDHC) deficiency is a rare inherited metabolic disorder.
- It leads to lactic acidosis and can cause significant neurological impairment.
Observation:
- Two female patients, a 13-month-old infant and a 6-year-old, presented with developmental delay, lactic acidosis, visual disturbance, and epileptic fits.
- Muscle biopsies revealed markedly decreased PDHC activity (16% of normal) in both patients.
- Histochemistry showed disorganized muscle fiber networks, increased nonspecific esterase activity, and basophilic fibers, but lacked ragged-red fibers and lipid accumulation.
Findings:
- Electron microscopy showed mostly normal mitochondria, with focal subsarcolemmal aggregates of mildly enlarged mitochondria.
- Morphometric analysis did not reveal significant differences in mean mitochondrial size or mitochondrial volume percentage compared to controls.
- These findings suggest specific mitochondrial alterations secondary to PDHC deficiency.
Implications:
- This study highlights the diagnostic utility of muscle biopsy in identifying PDHC deficiency.
- Understanding these specific muscle histopathology findings aids in diagnosing and managing patients with this condition.
- Further research into the pathomechanisms of mitochondrial changes in PDHC deficiency is warranted.
Abstract:
Muscle biopsies from a 13-month-old female infant with a delay in developmental milestones, lactic acidosis and visual disturbance, and a 6 year-old female with frequent epileptic fits are described. Biochemical studies of biopsied muscles and skin fibroblasts demonstrated markedly decreased pyruvate dehydrogenase complex (PDHC) activity to about 16% of normal value. Muscle histochemistry in both patients showed disorganized intermyofibrillar networks containing large diformazan granules on NADH-TR, small angulated fibers with high nonspecific esterase (NSE) activity and basophilic fibers. Ragged-red fibers and increased lipid droplet accumulation were absent. Patient 1 had increased numbers of type 2C fibers (11.3%) and mild fiber type grouping. On electron microscopy, most mitochondria were nearly normal. There were focal aggregates of mildly enlarged mitochondria in the subsarcolemmal areas in both patients. Morphometric study showed that the mean mitochondrial size and the mitochondrial percentage of fiber volume were not significantly different amongst patients and normal controls.