Medication Summary

Sodium dichloroacetate is a compound that is believed to activate the PDC by inhibiting the inactivating kinase, resulting in decreased lactate production and promotion of pyruvate oxidation.

Acute decompensation during illness in patients with PCD requires management of the acidosis with hydration and intravenous bicarbonate.

Class Summary

Dichloroacetate (DCA) sodium is the only drug found to activate the enzyme complex.

Sodium dichloroacetate

Designated as an orphan drug in the United States. Used to treat lactic acidosis. This is a compound that is believed to activate the PDC by inhibiting the inactivating kinase, resulting in decreased lactate production and promotion of pyruvate oxidation.

Class Summary

Sodium bicarbonate is used as a gastric, systemic, and urinary alkalinizer and has been used in the treatment of acidosis resulting from metabolic and respiratory causes, including diabetic coma, diarrhea, kidney disturbances, and shock. Sodium bicarbonate also increases renal clearance of acidic drugs.

Sodium bicarbonate

View full drug information

Bicarbonate can be used to correct the acidosis in chronic and acute settings.

Citrate solutions (Bicitra, Polycitra)

View full drug information

Several solutions containing citrate with sodium or potassium or both are available as alkalinizing agents. With normal hepatic function, 1 mEq of citrate is converted to 1 mEq of bicarbonate.

Follow-up

Rezende LR, Souza PB, Pereira GRM, Lugon JR. Metabolic acidosis in hemodialysis patients: a review. J Bras Nefrol. 2017 Jul-Sep. 39 (3):305-311. [QxMD MEDLINE Link]. [Full Text].
Monnot S, Serre V, Chadefaux-Vekemans B, et al. Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. Hum Mutat. 2009 May. 30(5):734-40. [QxMD MEDLINE Link].
Ostergaard E, Duno M, Møller LB, Kalkanoglu-Sivri HS, Dursun A, Aliefendioglu D, et al. Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. JIMD Rep. 2013. 9:1-5. [QxMD MEDLINE Link]. [Full Text].
Marin-Valencia I, Roe CR, Pascual JM. Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. Mol Genet Metab. 2010 Sep. 101(1):9-17. [QxMD MEDLINE Link].
De Meirleir L. Disorders of pyruvate metabolism. Handb Clin Neurol. 2013. 113:1667-73. [QxMD MEDLINE Link].
Miyamoto T, Amrein H. Gluconeogenesis: An ancient biochemical pathway with a new twist. Fly (Austin). 2017 Jul 3. 11 (3):218-223. [QxMD MEDLINE Link]. [Full Text].
Messner CB, Driscoll PC, Piedrafita G, De Volder MFL, Ralser M. Nonenzymatic gluconeogenesis-like formation of fructose 1,6-bisphosphate in ice. Proc Natl Acad Sci U S A. 2017 Jul 11. 114 (28):7403-7407. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. 2005 Jun. 41(6):1407-32. [QxMD MEDLINE Link].
Al-Essa MA, Ozand PT. Manual of Metabolic Disease. 1st ed. Riyadh, Saudi Arabia: King Faisal Specialist Hospital and Research Centre; 1998.
Augereau C, Pham Dinh D, Moncion A. Pyruvate carboxylase deficiencies: complementation studies between "French" and "American" phenotypes in cultured fibroblasts. J Inherit Metab Dis. 1985. 8(2):59-62. [QxMD MEDLINE Link].
Bartlett K, Ghneim HK, Stirk JH. Pyruvate carboxylase deficiency. J Inherit Metab Dis. 1984. 7 Suppl 1:74-8. [QxMD MEDLINE Link].
De Meirleir L. Defects of pyruvate metabolism and the Krebs cycle. J Child Neurol. 2002 Dec. 17 Suppl 3:3S26-33; discussion 3S33-4. [QxMD MEDLINE Link].
Garcia-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P. Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. Ann Neurol. 2006 Jan. 59(1):121-7. [QxMD MEDLINE Link].
Higgins JJ, Glasgow AM, Lusk M. MRI, clinical, and biochemical features of partial pyruvate carboxylase deficiency. J Child Neurol. 1994 Oct. 9(4):436-9. [QxMD MEDLINE Link].
Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D. Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. Mol Genet Metab. 2005 Apr. 84(4):305-12. [QxMD MEDLINE Link].
Nyhan WL, Khanna A, Barshop BA. Pyruvate carboxylase deficiency--insights from liver transplantation. Mol Genet Metab. 2002 Sep-Oct. 77(1-2):143-9. [QxMD MEDLINE Link].
Perry TL, Haworth JC, Robinson BH. Brain amino acid abnormalities in pyruvate carboxylase deficiency. J Inherit Metab Dis. 1985. 8(2):63-6. [QxMD MEDLINE Link].
Robinson BH. Lactic acidemia and mitochondrial disease. Mol Genet Metab. 2006 Sep-Oct. 89(1-2):3-13. [QxMD MEDLINE Link].
Roe CR, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis. 2006 Apr-Jun. 29(2-3):332-40. [QxMD MEDLINE Link].
Schiff M, Levrat V, Acquaviva C, Vianey-Saban C, Rolland MO, Guffon N. A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation. Mol Genet Metab. 2006 Feb. 87(2):175-7. [QxMD MEDLINE Link].
Stacpoole PW, Barnes CL, Hurbanis MD. Treatment of congenital lactic acidosis with dichloroacetate [see comments]. Arch Dis Child. 1997 Dec. 77(6):535-41. [QxMD MEDLINE Link].
Ullrich K, Schmidt H, van Teeffelen-Heithoff A. Glycogen storage disease type I and III and pyruvate carboxylase deficiency: results of long-term treatment with uncooked cornstarch. Acta Paediatr Scand. 1988 Jul. 77(4):531-6. [QxMD MEDLINE Link].
Van Coster RN, Janssens S, Misson JP. Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples. Prenat Diagn. 1998 Oct. 18(10):1041-4. [QxMD MEDLINE Link].

Media Gallery

This is a diagrammatic representation of the citric acid cycle and the abnormalities found in pyruvate carboxylase deficiency. The dotted line represents absent pathways. Pyruvate cannot produce oxaloacetate and is shunted to alternative pathways that produce lactic acid and alanine. The lack of oxaloacetate prevents gluconeogenesis and urea cycle function.

of 1