eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases

Pyruvate Dehydrogenase Complex Deficiency: Follow-up

Author: Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Coauthor(s): Paul J Benke, MD, PhD, Director of Clinical Genetics, Joe DiMaggio Children's Hospital
Contributor Information and Disclosures

Updated: Nov 6, 2009

Follow-up

Further Inpatient Care

  • Acute decompensation during acute pyruvate dehydrogenase complex (PDC) deficiency (PDCD) requires admission and management of acidosis with intravenous bicarbonate.

Further Outpatient Care

  • Provide close follow-up for children with pyruvate dehydrogenase complex deficiency. Closely monitor lactate levels.
  • To help evaluate dietary manipulations and to ensure compliance, have caregivers of children with pyruvate dehydrogenase complex deficiency complete a dietary log.
  • Advise caregivers of individuals with pyruvate dehydrogenase complex deficiency to always carry an informational statement that describes pyruvate dehydrogenase complex deficiency and the appropriate medical treatment for the disorder in an emergency setting.

Prognosis

  • Individuals with mild deficiencies in the E1 enzyme of the pyruvate dehydrogenase complex have a better prognosis than those with deficiencies in the E2 and E3 pyruvate dehydrogenase complex enzymes.
  • Prediction of prognosis is unclear because of the small number of children with pyruvate dehydrogenase complex deficiency studied and the large number of mutations involved.
  • In most cases of neonatal-onset and infantile-onset of pyruvate dehydrogenase complex deficiency, a poor prognosis remains, even when the lactic acidosis is treated successfully. Although lactic acidosis appears to be controlled by thiamine supplementation in individuals who respond to thiamine, the neurological outcome may be poor.
  • One case report describes cessation of neurological demyelination with the ketogenic diet; however, the ketogenic diet has not been reported to be of significant neurologic benefit to other patients with pyruvate dehydrogenase complex deficiency.5
  • Dichloroacetate appears to produce biochemical correction of pyruvate dehydrogenase complex deficiency in many cases, but resolution of neurologic symptoms is exceptional. Structural CNS abnormalities likely cannot be reversed with successful biochemical treatment.
  • Dichloroacetate may have greater efficacy with particular mutations of the E1 subunit.
  • In general, treatment of individuals with pyruvate dehydrogenase complex deficiency is most beneficial if started early. Although successful treatment is rare, some cases have been reported.
  • Although the recurrence rate for subsequent pregnancies is low, test future gestations for pyruvate dehydrogenase complex deficiency because of the possibility of germline mosaicism. Enzyme activity of cultured chorionic villus cells can be determined in time to make an early diagnosis. Inaccuracies in the diagnosis of the female fetus arise from X chromosome inactivation.
  • Individuals with an E2 subunit deficiency may have a mild phenotype.

Patient Education

  • Educate the patient with pyruvate dehydrogenase complex deficiency and the caregivers regarding the factors that may elicit a crisis and the early signs of decompensation.
 


More on Pyruvate Dehydrogenase Complex Deficiency

Overview: Pyruvate Dehydrogenase Complex Deficiency
Differential Diagnoses & Workup: Pyruvate Dehydrogenase Complex Deficiency
Treatment & Medication: Pyruvate Dehydrogenase Complex Deficiency
Follow-up: Pyruvate Dehydrogenase Complex Deficiency
Multimedia: Pyruvate Dehydrogenase Complex Deficiency
References
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References

  1. Ostergaard E, Moller LB, Kalkanoglu-Sivri HS, et al. Four novel PDHA1 mutations in pyruvate dehydrogenase deficiency. J Inherit Metab Dis. Jun 11 2009;[Medline].

  2. 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].

  3. 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].

  4. [Best Evidence] Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. May 2006;117(5):1519-31. [Medline].

  5. 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].

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

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  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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].

  13. 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].

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

  15. 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].

  16. 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].

  17. 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].

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Further Reading

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Keywords

pyruvate dehydrogenase complex deficiency, PDCD, congenital infantile lactic acidosis, intermittent ataxia with lactic acidosis, developmental delay, X-linked Leigh syndrome, treatment, diagnosis

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Contributor Information and Disclosures

Author

Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center 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 Academy of Pediatrics and American Society of Human Genetics
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert Anthony Saul, MD, Clinical Professor, Department of Pediatrics, University of South Carolina; 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.

CME Editor

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, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, 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.

 
 
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