CoChat
Sign Up
Cited by 278Metabolism and Genetic DisordersBiochemical Acid Research StudiesMitochondrial Function and Pathology

The spectrum of pyruvate dehydrogenase complex deficiency: Clinical, biochemical and genetic features in 371 patients

Open access
Patel, Kavi P., O'Brien, Thomas W., Subramony, Sankarasubramon H., Shuster, Jonathan, Stacpoole, Peter W.·2012·Molecular Genetics and Metabolism
DOI 10.1016/j.ymgme.2011.09.032PMC PMC3754811
Open this paper in CoChat — free account

Abstract

Context Pyruvate dehydrogenase complex (PDC) deficiency is a genetic mitochondrial disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration and, usually, death during childhood. There has been no recent comprehensive analysis of the natural history and clinical course of this disease.Objective We reviewed 371 cases of PDC deficiency, published between 1970 and 2010, that involved defects in subunits E1α and E1β and components E1, E2, E3 and the E3 binding protein of the complex.Data sources and extraction English language peer-reviewed publications were identified, primarily by using PubMed and Google Scholar search engines.Results Neurodevelopmental delay and hypotonia were the commonest clinical signs of PDC deficiency. Structural brain abnormalities frequently included ventriculomegaly, dysgenesis of the corpus callosum and neuroimaging findings typical of Leigh syndrome. Neither gender nor any clinical or neuroimaging feature differentiated the various biochemical etiologies of the disease. Patients who died were younger, presented clinically earlier and had higher blood lactate levels and lower residual enzyme activities than subjects who were still alive at the time of reporting. Survival bore no relationship to the underlying biochemical or genetic abnormality or to gender.Conclusions Although the clinical spectrum of PDC deficiency is broad, the dominant clinical phenotype includes presentation during the first year of life; neurological and neuromuscular degeneration; structural lesions revealed by neuroimaging; lactic acidosis and a blood lactate:pyruvate ratio ≤20.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.ymgme.2011.09.032

Cites

199 of 199 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PDC deficiency is sufficient to rewire energy metabolism towards aerobic glycolysis despite the potential adaptive node for TCA cycle anaplerosis mediated by PC.

    “PDC deficiency is sufficient to rewire energy metabolism towards aerobic glycolysis despite the potential adaptive node for TCA cycle anaplerosis (a process to replenish TCA cycle intermediates), mediated by PC.28”

    From The multifaceted contributions of mitochondria to cellular metabolism (2018) · cites this paper as [28]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 14

  1. [8]DeBrosse SD Okajima K Schmotzer CL Frohnapfel MB Kerr DS Spectrum of Clinical Outcomes in Pyruvate Dehydrogenase Deficiency United Mitochondrial Disease Foundation Annual Symposium 6 15-19 2011 Chicago, IL Manuscript in preparation
  2. [9]Patel K Stacpoole PW The Spectrum of Pyruvate Dehydrogenase Complex Deficiency: Clinical, Biochemical and Genetic Features in 366 Patients United Mitochondrial Disease Foundation Annual Symposium 6 15-19 2011 Chicago, IL Manuscript in preparation
  3. [139]Ramadan DG Head RA Al-Tawari A Habeeb Y Zaki M Al-Ruqum F Besley GT Wraith JE Brown RM Brown GK Lactic acidosis and developmental delay due to deficiency of E3 binding protein (protein X) of the pyruvate dehydrogenase complex J Inherit Metab Dis 27 2004 477 485 15303005
  4. [173]Robinson BH Sherwood WG Lactic acidemia, the prevalence of pyruvate decarboxylase deficiency J Inherit Metab Dis 7 1984 69 6434848
  5. [183]Okajima K Warman ML Byrne LC Kerr DS Somatic mosaicism in a male with an exon skipping mutation in PDHA1 of the pyruvate dehydrogenase complex results in a milder phenotype Mol Genet Metab 87 2006 162 68 16412675
  6. [187]Cameron JM Levandovskiy V MacKay N Tein I Deficiency of pyruvate dehydrogenase caused by novel and known mutations in the E1α subunit Am J Med Genet 131A 2004 59 66 15384102
  7. [188]Brivet M Moutard ML Zater M Venet L First characterization of a large deletion of the PDHA1 gene Mol Genet Metab 86 2004 456 61 16256390
  8. [190]Soares-Fernandes JP Teixeira-Gomes R Cruz R Ribeiro M M Neonatal pyruvate dehydrogenase deficiency due to a R302H mutation in the PDHA1 gene: MRI findings Pediatr Radiol 38 2008 559 62 18197404
  9. [192]Ostergaard E Birk Moller L Serap Kalkanoglu-Sivri H Dursun A Four novel PDHA1 mutations in pyruvate dehydrogenase deficiency J Inherit Metab Dis 115 2009 123 27 19517265
  10. [193]Berendzen K Theriaque DW Shuster J Stacpoole PW Therapeutic potential of dichloroacetate for pyruvate dehydrogenase complex deficiency Mitochondrion 6 2006 126 135 16725381
  11. [194]Kerr DS Treatment of congenital lactic acidosis: a review Int Pediatr 10 1995 75 81
  12. [195]Falk RE Cederbaum SD Blass JP Gibson GE Ketogenic diet in the management of pyruvate dehydrogenase deficiency Pediatrics 58 1976 713 21 824610
  13. [197]Whitehouse S Cooper RH Randle PJ Mechanism of activation of pyruvate dehydrogenase by dichloroacetate and other halogenated carboxylic acids Biochem J 141 1974 761 774 4478069 PMC1168183
  14. [203]Patel K Stacpoole PW The Spectrum of Pyruvate Dehydrogenase Complex Deficiency: Clinical Biochemical and Genetic Features in 366 Patients United Mitochondrial Disease Foundation Annual Symposium June 15-19 2011 Chicago, IL Manuscript in preparation

Cited by

Sorted by citations

Related

Authors
Patel, K. P., O'Brien, T. W., Subramony, S. H., Shuster, J., & Stacpoole, P. W.
Affiliations
  • University of Florida Health (US)
  • University of Florida (US)
Corresponding author
Stacpoole, Peter W.
ORCID
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2012-01
Volume
105
Issue
1
Pages
34-43
ISSN
1096-7192 (ISSN-L)
DOI
10.1016/j.ymgme.2011.09.032
PMC
PMC3754811
OpenAlex
W1978119925
Cited by
278
References
199
Citations by year
2026: 16 · 2025: 17 · 2024: 13 · 2023: 15 · 2022: 21 · 2021: 26 · 2020: 30 · 2019: 22 · 2018: 22 · 2017: 22 · 2016: 16 · 2015: 16 · 2014: 19 · 2013: 12 · 2012: 11
FWCI
1.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Genetics and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH
  • University of Florida's Clinical and Translational Science Institute
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
pyruvate dehydrogenase deficiency, mitochondrial disease, lactic acidosis, neurodevelopmental delay, hypotonia, ventriculomegaly, Leigh syndrome, natural history (disease), survival, residual enzyme activity
MeSH terms
Female, Humans, Male, Pyruvate Dehydrogenase Complex, Sex Characteristics, Pyruvate Dehydrogenase Complex Deficiency Disease, Treatment Outcome, Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review