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[Suspected pyruvate carboxylase deficiency in 4 children with Leigh disease]
Insights
Subacute necrotizing encephalomyelopathy of Leigh, a rare neurological disorder, presents with specific clinical and biochemical changes in children. Investigations revealed elevated lactic and pyruvic acid levels, suggesting impaired pyruvate metabolism.
Area of Science:
- Biochemistry
- Neurology
- Pediatrics
Background:
- Subacute necrotizing encephalomyelopathy (SNE), or Leigh disease, is a severe genetic neurometabolic disorder.
- Early diagnosis and understanding of metabolic derangements are crucial for managing Leigh disease.
Observation:
- Clinical presentation in four children included developmental delay, progressive neurological deficits (weakness, ataxia, nystagmus), and distinctive skin changes.
- Biochemical analysis revealed elevated serum lactic acid, pyruvic acid, and alanine, alongside metabolic acidosis.
Findings:
- Intravenous glucose and alanine loading tests suggested reduced pyruvate carboxylase activity in affected children.
- Postmortem examination in one case confirmed the neuropathological hallmarks of Leigh disease.
Implications:
- These findings highlight the utility of pyruvate metabolism investigations in diagnosing Leigh disease.
- Understanding these metabolic alterations can guide future therapeutic strategies for SNE.
Abstract:
Clinical observations and results of investigations of pyruvic acid metabolism are reported in 4 children in whom subacute necrotizing encephalomyelopathy of Leigh was diagnosed intravitally. Attention is called to the similarity of the clinical manifestations with its onset in the first year of life, deficient body weight and growth, progressing neurological disturbances (weakening of muscle power, tremor, ataxia, nystagmus), course with periods of exacerbations, tachypnoea, skin changes (hirsutism, telangiectasia, perspiration), death at the age of 2-3 years. The biochemical changes in all children included raised serum levels of lactic acid, pyruvic acid and alanine, and acid-base equilibrium disturbances with metabolic acidosis (relatively balanced respiratory alkalosis). The results of the test of intravenous loading with glucose and alanine carried out in all children indicated indirectly reduced activity of pyruvate carboxylase. In one child histological examination of the brain carried out postmortem confirmed the diagnosis of Leigh's disease.