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Investigating chronic metabolic acidosis in children is crucial for identifying organic acidemias, particularly lactic acid. Early diagnosis aids in managing rare conditions like Leigh syndrome and other metabolic disorders.
Area of Science:
- Biochemistry
- Pediatrics
- Metabolic Disorders
Background:
- Chronic metabolic acidosis in children warrants investigation for organic acid presence, especially with anion deficits.
- Lactic acid is a key organic acid to consider in such pediatric cases.
Observation:
- This essay focuses on chronic lactic acidosis in infancy, excluding hypoxia-related or exogenous causes.
- Rare causes include glycogen storage disease Type 1, fructose diphosphatase deficiency, and various acidemias.
- An idiopathic group of chronic lactic acidosis exists, likely with diverse metabolic origins.
Findings:
- Leigh syndrome (SNE) involves a block in thiamine triphosphate formation, linked to an inhibitor of TPP-ATP phosphoryl transferase.
- Elevated lactate, pyruvate, and alanine are common in SNE, but their causal role in pyruvate catabolism is unclear.
- Disturbed lactate and pyruvate metabolism is also seen in other conditions like mitochondrial myopathies and Wernicke's encephalopathy.
Implications:
- Identifying specific organic acidemias is vital for targeted pediatric metabolic disorder management.
- Understanding the role of pyruvate metabolism disturbances can improve diagnosis and treatment strategies.
- Further research into idiopathic chronic lactic acidosis may reveal novel metabolic pathways and therapeutic targets.
Abstract:
Children with chronic metabolic acidosis should be investigated to determine the presence of an organic acid, especially when the plasma electrolyte profile shows a deficiency of anion. One of the organic acids that should be looked for in such a patient is lactic acid. Lactic acidosis due to tissue hypoxia is a well-known phenomenon (e.g., in shock and cardiopulmonary disease) and has not been discussed in this essay; nor has lactic acidosis due to exogenous causes like infusion of fructose or sorbitol, or admiministration of phenformin. Chronic lactic acidosis in infancy is a rare condition. It may be associated with glycogen storage disease Type 1, fructose diphosphatase deficiency, methylmalonic acidemia, propionic acidemia, pyruvate carboxylase or dehydrogenase deficiency and Leigh's subacute necrotizing encephalomyelopathy (SNE). Some patients with chronic lactic acidosis do not have nay of these diseases and comprise an "idiopathic" group. This is a heterogeneous group, probably having several different causes for the metabolic error. In Leigh's SNE, a metabolic block in the formation of thiamine triphosphate in brain has been demonstrated and has been attributed to the presence of an inhibitor of thiamine pyrophosphate-adenosine triphosphate (TPP-ATP) phosphoryl transferase in body fluids. The inhibitor has also been encountered in cases of intermittent cerebellar ataxia and of primary hypoventilation (Ondine's curse), which may represent variants of Leigh's disease. Increased blood levels of lactate, pyruvate and alanine frequently are encountered in SNE, but it still is not clear whether they are due to a primary or secondary disturbance in the catabolism of pyruvate. Disturbed lactate and pyruvate metabolism has also been encountered in isolated cases of mental retardation and growth failure, in mitochondrial myopathies and in polyneuropathies, and may be expected to occur in Wernicke's encephalopathy. Finally, it has been noted in malignancy and in association with other rare metabolic disorders.