Pyruvate Dehydrogenase Complex Deficiency Medication

  • Author: Richard E Frye, MD, PhD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 12, 2012
 

Medication Summary

Cofactor supplementation with thiamine, carnitine, and lipoic acid is the standard of care. The cases of pyruvate dehydrogenase complex deficiency (PDCD) that are responsive to these cofactors respond to supplementation, especially thiamine. Some evidence suggests that high doses of thiamine may be most effective in some mutations causing thiamine-responsive pyruvate dehydrogenase complex deficiency. However, administration of all of these cofactors to all patients with pyruvate dehydrogenase complex deficiency is typical in order to optimize pyruvate dehydrogenase complex function.

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Cofactors

Class Summary

Organic substances required by the body in small amounts for various metabolic processes. They are essential for new cell growth and division. They are used clinically for the prevention and treatment of specific deficiency states.

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Biotin

 

Essential cofactor for several important enzymes, including an alternative pathway for pyruvate. Vitamin H is a synonym.

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Thiamine (Thiamilate)

 

Important cofactor for the pyruvate dehydrogenase complex E1 enzyme. Some disorders are responsive to simple supplementation.

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Enzyme activator

Class Summary

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

Dichloroacetate sodium

 

A compound believed to activate the PDC by inhibiting the inactivating kinase. This decreases lactate production and promotes pyruvate oxidation.

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Alkalinizing agents

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. Citric acid mixtures may also be used. With normal hepatic function, 1 mEq of citrate is converted to 1 mEq of bicarbonate.

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Sodium bicarbonate

 

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

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Citrate mixtures (Bicitra, Oracit, Cytra-K)

 

Several mixtures of 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.

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Contributor Information and Disclosures
Author

Richard E Frye, MD, PhD  Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Medical School at Houston

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and International Neuropsychological Society

Disclosure: Nothing to disclose.

Coauthor(s)

Paul J Benke, MD, PhD  Director of Clinical Genetics, Joe DiMaggio Children's Hospital

Paul J Benke, MD, PhD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Ian Krantz, MD  Department of Pediatrics, Assistant Professor, University of Pennsylvania and Children's Hospital of Philadelphia

Ian Krantz, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Robert Anthony Saul, MD  Clinical Professor, Department of Pediatrics, University of South Carolina School of Medicine; Senior Clinical Geneticist, Greenwood Genetic Center

Robert Anthony Saul, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics, and American College of Physician Executives

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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This diagram shows a simplified version of the citric acid cycle and shows the enzyme deficit. The dashed line indicates the blocked pathway and the size of the arrows indicates the relative flow of products. Because pyruvate does not proceed to acetyl-coenzyme A (CoA), it is shunted to other pathways that produce lactic acid and alanine.
 
 
 
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