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Pyruvate carboxylase deficiency--insights from liver transplantation
William L Nyhan1, Ajai Khanna, Bruce A Barshop
1Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. WNyahan@USCD.edu
Insights
Pyruvate carboxylase deficiency causes severe metabolic acidosis in infants. While glucose helped ketoacidosis, liver transplantation successfully treated ketoacidosis and improved lactic acidosis in one infant.
Area of Science:
- Biochemistry
- Pediatric Medicine
- Metabolic Disorders
Background:
- Pyruvate carboxylase deficiency (PCD) is a rare genetic disorder.
- The complex form presents with lethal metabolic acidosis, ketoacidosis, lactic acidemia, renal tubular acidosis, hyperammonemia, and citrullinemia.
Observation:
- In an infant with PCD, high glucose levels initially improved ketoacidosis but exacerbated lactic acidosis.
- Orthotopic liver transplantation was performed to address the metabolic derangements.
Findings:
- Liver transplantation completely resolved ketoacidosis and renal tubular abnormalities.
- Lactic acidemia was ameliorated post-transplantation.
- Cerebrospinal fluid glutamine levels remained low and did not recover after transplantation.
Implications:
- Orthotopic liver transplantation is a potential therapeutic strategy for complex pyruvate carboxylase deficiency.
- The persistent low CSF glutamine suggests ongoing metabolic dysfunction or limited substrate availability despite successful liver transplant.
- Further research is needed to understand the long-term neurological outcomes and metabolic management in PCD patients.
Abstract:
Pyruvate carboxylase deficiency, complex form, presents in early infancy with lethal metabolic acidosis, resulting from ketoacidosis and lactic acidemia. Renal tubular acidosis, hyperammonemia, and citrullinemia complete the picture. In an infant with this disease, large amounts of glucose ameliorated the ketoacidosis, but worsened the lactic acidosis. Orthotopic hepatic transplantation completely reversed the ketoacidosis and the renal tubular abnormality and ameliorated the lactic acidemia. Concentrations of glutamine in cerebrospinal fluid were low and did not improve with liver transplantation.