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Propionic acidemia and hyperlysinemia in a case with ornithine transcarbamylase (OTC) deficiency
Insights
This study describes a female infant with episodic hyperammonemia, a urea cycle disorder, and elevated short-chain fatty acids. Researchers suggest ammonia and lysine compete for alpha-ketoglutarate, linking urea cycle and fatty acid metabolism disorders.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Urea cycle disorders (UCDs) are genetic conditions causing hyperammonemia.
- Short-chain fatty acid (SCFA) elevations can occur in metabolic disorders.
- Lysine metabolism disorders can present with hyperammonemia.
Observation:
- A female infant presented with episodic hyperammonemia, hyperlysinemia, and elevated propionate levels during hyperammonemic attacks.
- Enzyme studies ruled out propionic acidemia.
- Diagnosis of ornithine transcarbamylase (OTC) deficiency was confirmed through enzyme activity, hyperammonemia response, orotic aciduria, and inheritance patterns.
Findings:
- The patient exhibited homocitrullinuria and epsilon-N-acetyl-l-lysine in urine, suggesting saccharopine pathway deficiency.
- Alpha-ketoglutarate reductase activity was normal in fibroblasts.
- Metabolite changes occurred only with hyperammonemia, not after lysine load, indicating potential competition between ammonia and lysine for alpha-ketoglutarate.
Implications:
- This case highlights a potential interaction between urea cycle dysfunction and lysine metabolism.
- The findings suggest a novel mechanism where ammonia may interfere with lysine degradation pathways.
- Further research is needed to elucidate the link between urea cycle disorders and short-chain fatty acid metabolism.
Abstract:
A female infant with episodic hyperammonemia due to a disorder of the urea cycle and who had hyperlysinemia and an unusual elevation of short chain fatty acids, mainly propionate, is described. Both occurred apparently only during attacks of hyperammonemia. Propionic acidemia was ruled out by enzyme studies. OTC deficiency was diagnosed on the basis of: 1) decreased enzyme activity in leukocytes;2) hyperammonemia in response to protein intakes in excess of 2.0 g/kg/day; 3) orotic aciduria in the patient and her asymptomatic mother; 4) suggestive evidence of x-linked dominant inheritance; and 5) exclusion of citrullinemia, argininosuccinic aciduria, argininemia, and disorders of lysine metabolism that are associated with hyperammonemia. Homocitrullinuria, presence of epsilon-N-acetyl-l-lysine in urine, and absence of saccharopine indicate deficiency of the saccharopine pathway of lysine degradation. However, alpha-ketoglutarate reductase was normal in fibroblasts. Since these metabolites were observed only in conjunction with hyperammonemia but not after a lysine load, we suggest that there was competition between ammonia and lysine for alpha-ketoglutarate. The link between disorders of the urea cycle and short chain fatty acid metabolism remains unexplained..