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Pyruvate carboxylase deficiency: acute exacerbation after ACTH treatment of infantile spasms
S L Rutledge1, O C Snead, D R Kelly
1Department of Pediatrics, University of Alabama School of Medicine, Birmingham.
Insights
Pyruvate carboxylase deficiency causes severe lactic acidosis in infants. Adrenocorticotrophin hormone (ACTH) therapy may precipitate this condition, highlighting a critical treatment consideration.
Area of Science:
- Biochemistry
- Pediatric Neurology
- Metabolic Disorders
Background:
- Pyruvate carboxylase deficiency is a rare genetic disorder leading to congenital lactic acidosis.
- Infantile spasms are a severe form of epilepsy in infants, often treated with adrenocorticotrophin hormone (ACTH).
Observation:
- A child with infantile spasms treated with ACTH developed severe lactic acidosis.
- Elevated blood lactate, pyruvate, and alanine, along with cerebrospinal fluid alanine, were noted.
- Plasma alanine levels doubled during ACTH therapy, and fibroblast pyruvate carboxylase activity was extremely low.
Findings:
- The patient was diagnosed with pyruvate carboxylase deficiency.
- ACTH therapy appeared to precipitate a catastrophic metabolic acidosis in this patient.
- Autopsy revealed brain cystic degeneration and demyelination.
Implications:
- Pyruvate carboxylase deficiency presents with neonatal acidosis, developmental delay, seizures, hypotonia, and early mortality.
- ACTH therapy should be carefully considered in patients with potential or diagnosed pyruvate carboxylase deficiency due to the risk of precipitating severe acidosis.
- This case underscores the critical interaction between metabolic status and therapeutic interventions in pediatric patients.
Abstract:
Pyruvate carboxylase deficiency results in congenital lactic acidosis. We report the significant finding in a child with infantile spasms controlled with adrenocorticotrophin hormone (ACTH) but who then developed severe lactic acidosis; pyruvate carboxylase deficiency was subsequently diagnosed. Blood lactate, pyruvate, and alanine levels were elevated, as well as cerebrospinal fluid alanine. Plasma alanine concentration was doubled by ACTH therapy. Fibroblasts contained extremely low pyruvate carboxylase activity. The patient died at 12 weeks of age after recurrent episodes of profound acidosis. At autopsy, the brain manifested cystic degeneration and demyelination. Pyruvate carboxylase deficiency is associated with neonatal onset of acidosis, delayed development, seizures, hypotonia, recurrent profound acidosis, and early death. The dramatic rise in plasma alanine content coincident with ACTH therapy suggest that ACTH played a role in precipitating the catastrophic metabolic acidosis.