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[A case of complex I deficiency with episodic respiratory distress]
Insights
This study identifies a rare myopathic form of mitochondrial complex I deficiency in a child presenting with episodic respiratory distress and lactic acidosis. This presentation is distinct from typical complex I deficiency neurological symptoms.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Mitochondrial complex I deficiency is a common inherited metabolic disorder.
- It typically presents with neurological symptoms, including developmental delay, seizures, and stroke-like episodes.
Observation:
- A 7-year-old girl exhibited easy fatigability, respiratory distress, and lactic acidosis.
- Muscle biopsy revealed a myopathic pattern with ragged-red fibers and decreased mitochondrial complex I activity.
- Biochemical analysis showed reduced NADH cytochrome c reductase activity and decreased complex I subunits.
Findings:
- The patient was diagnosed with the myopathic form of complex I deficiency, characterized by muscle symptoms without central nervous system involvement.
- Oxograph studies confirmed deficient oxygen consumption in isolated mitochondria with malate and pyruvate substrates.
- Episodic respiratory distress was a novel clinical manifestation not previously reported in complex I deficiency.
Implications:
- This case expands the clinical spectrum of mitochondrial complex I deficiency.
- Highlights the importance of considering mitochondrial disorders in pediatric patients with unexplained respiratory distress and metabolic acidosis.
- Suggests that the myopathic form may present without typical neurological sequelae.
Abstract:
A 7-year-old girl with normal psychomotor development during infancy began to have easy fatigability about 3 years of age. At the age of 5 years, she developed respiratory distress and became unconscious when the serum lactate and pyruvate levels were markedly elevated and a blood gas analysis showed respiratory and metabolic acidosis. Thereafter, she had similar episodic respiratory problems with lactic acidosis. Her muscle biopsy showed a myopathic pattern and numerous ragged-red fibers in an approximately half of muscle fibers. Lipid droplets were slightly to moderately increased in amount mostly in the ragged-red fibers. A biochemical analysis on the isolated mitochondria from the biopsied sample showed markedly decreased NADH cytochrome c reductase activity with no specific but rather uniformly decreased subunits of complex I by the immunoblotting method. She was diagnosed as having the myopathic form of complex I deficiency because she and her relatives with similar muscle symptoms had no central nervous system symptoms such as progressive mental deterioration, convulsions and stroke-like episodes. Diagnosis of complex I deficiency was further confirmed by an oxograph study; the oxygen consumption was not detectable when malate and pyruvate were added as the substrates in the isolated mitochondria. Although stroke-like episodes and convulsions are commonly seen in complex I deficiency, episodic respiratory distress as seen in the present patient has not been described in the literature.