Pyruvate Dehydrogenase Complex Deficiency Differential Diagnoses

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

Differential Diagnoses

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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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  2. Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. Jan 2012;105(1):34-43. [Medline].

  3. Giribaldi G, Doria-Lamba L, Biancheri R, Severino M, Rossi A, Santorelli FM, et al. Intermittent-relapsing pyruvate dehydrogenase complex deficiency: a case with clinical, biochemical, and neuroradiological reversibility. Dev Med Child Neurol. Dec 5 2011;[Medline].

  4. Han Z, Zhong L, Srivastava A, Stacpoole PW. Pyruvate dehydrogenase complex deficiency due ubiquitination and proteasome-mediated degradation of the E1beta subunit. J Biol Chem. Oct 8 2007;[Medline].

  5. Debray FG, Mitchell GA, Allard P, Robinson BH, Hanley JA, Lambert M. Diagnostic accuracy of blood lactate-to-pyruvate molar ratio in the differential diagnosis of congenital lactic acidosis. Clin Chem. May 2007;53(5):916-21. [Medline].

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  7. Weber TA, Antognetti MR, Stacpoole PW. Caveats when considering ketogenic diets for the treatment of pyruvate dehydrogenase complex deficiency. J Pediatr. Mar 2001;138(3):390-5. [Medline].

  8. Al-Essa MA, Ozand PT. Manual of Metabolic Diseases. Saudi Arabia: King Faisal Specialist Hospital and Research Centre, Riyadh; 1998.

  9. Brown GK, Otero LJ, LeGris M, Brown RM. Pyruvate dehydrogenase deficiency. J Med Genet. Nov 1994;31(11):875-9. [Medline].

  10. Byrd DJ, Krohn HP, Winkler L, et al. Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia. Eur J Pediatr. Apr 1989;148(6):543-7. [Medline].

  11. De Meirleir L. Defects of pyruvate metabolism and the Krebs cycle. J Child Neurol. Dec 2002;17 Suppl 3:3S26-33; discussion 3S33-4. [Medline].

  12. Debray FG, Lambert M, Vanasse M, Decarie JC, Cameron J, Levandovskiy V. Intermittent peripheral weakness as the presenting feature of pyruvate dehydrogenase deficiency. Eur J Pediatr. Jul 2006;165(7):462-6. [Medline].

  13. Fouque F, Brivet M, Boutron A, et al. Differential effect of DCA treatment on the pyruvate dehydrogenase complex in patients with severe PDHC deficiency. Pediatr Res. May 2003;53(5):793-9. [Medline].

  14. Head RA, Brown RM, Zolkipli Z, et al. Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. Ann Neurol. Aug 2005;58(2):234-41. [Medline].

  15. Head RA, de Goede CG, Newton RW, et al. Pyruvate dehydrogenase deficiency presenting as dystonia in childhood. Dev Med Child Neurol. Oct 2004;46(10):710-2. [Medline].

  16. Morris AA, Leonard JV. The treatment of congenital lactic acidoses. J Inherit Metab Dis. 1996;19(4):573-80. [Medline].

  17. Morten KJ, Beattie P, Brown GK, Matthews PM. Dichloroacetate stabilizes the mutant E1alpha subunit in pyruvate dehydrogenase deficiency. Neurology. Aug 11 1999;53(3):612-6. [Medline].

  18. Naito E, Ito M, Yokota I, et al. Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency. J Neurol Sci. Sep 15 2002;201(1-2):33-7. [Medline].

  19. Naito E, Ito M, Yokota I, et al. Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region. Biochim Biophys Acta. Oct 9 2002;1588(1):79-84. [Medline].

  20. Pastoris O, Savasta S, Foppa P, et al. Pyruvate dehydrogenase deficiency in a child responsive to thiamine treatment. Acta Paediatr. May 1996;85(5):625-8. [Medline].

  21. Shevell MI, Matthews PM, Scriver CR, et al. Cerebral dysgenesis and lactic acidemia: an MRI/MRS phenotype associated with pyruvate dehydrogenase deficiency. Pediatr Neurol. Oct 1994;11(3):224-9. [Medline].

  22. Stacpoole PW, Barnes CL, Hurbanis MD, et al. Treatment of congenital lactic acidosis with dichloroacetate. Arch Dis Child. Dec 1997;77(6):535-41. [Medline].

  23. Stacpoole PW, Bunch ST, Neiberger RE, et al. The importance of cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis. J Pediatr. Jan 1999;134(1):99-102. [Medline].

  24. Zand DJ, Simon EM, Pulitzer SB, et al. In vivo pyruvate detected by MR spectroscopy in neonatal pyruvate dehydrogenase deficiency. AJNR Am J Neuroradiol. Aug 2003;24(7):1471-4. [Medline].

 
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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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