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Pyruvate dehydrogenase complex deficiency(PDHC)

MedGen UID:
19610
Concept ID:
C0034345
Disease or Syndrome
Synonyms: Ataxia with lactic acidosis 1; PDH DEFICIENCY; PDHC; Pyruvate decarboxylase deficiency; Pyruvate Dehydrogenase Complex Deficiency Disease; Pyruvate dehydrogenase deficiency
SNOMED CT: Deficiency of pyruvic decarboxylase (124593001); Deficiency of alpha-ketoacid carboxylase (124593001); Deficiency of alpha-carboxylase (124593001); Deficiency of pyruvate decarboxylase (124593001); Deficiency of pyruvate dehydrogenase (cytochrome) (46683007); Deficiency of pyruvic dehydrogenase (46683007); Ataxia with lactic acidosis (46683007); PDH - Pyruvate dehydrogenase deficiency (46683007); Pyruvate dehydrogenase deficiency (46683007); Pyruvate dehydrogenase complex deficiency (46683007); PDH deficiency (46683007); Ataxia with lactic acidosis I (46683007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Source: Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Related genes: PDHX, PDHB, PDHA1, DLD, DLAT
 
Monarch Initiative: MONDO:0019169
OMIM®: 312170
OMIM® Phenotypic series: PS312170
Orphanet: ORPHA765

Definition

Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Pyruvate dehydrogenase complex deficiency in Orphanet.

Professional guidelines

PubMed

Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC 3rd
Epilepsia 2015 May;56(5):707-16. Epub 2015 Mar 25 doi: 10.1111/epi.12954. PMID: 25818041
Rogovik AL, Goldman RD
Can Fam Physician 2010 Jun;56(6):540-2. PMID: 20547519Free PMC Article
Weber TA, Antognetti MR, Stacpoole PW
J Pediatr 2001 Mar;138(3):390-5. doi: 10.1067/mpd.2001.111817. PMID: 11241048

Recent clinical studies

Etiology

Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB
Orphanet J Rare Dis 2021 Jul 3;16(1):295. doi: 10.1186/s13023-021-01927-w. PMID: 34217336Free PMC Article
Sofou K, Dahlin M, Hallböök T, Lindefeldt M, Viggedal G, Darin N
J Inherit Metab Dis 2017 Mar;40(2):237-245. Epub 2017 Jan 18 doi: 10.1007/s10545-016-0011-5. PMID: 28101805Free PMC Article
Sperl W, Fleuren L, Freisinger P, Haack TB, Ribes A, Feichtinger RG, Rodenburg RJ, Zimmermann FA, Koch J, Rivera I, Prokisch H, Smeitink JA, Mayr JA
J Inherit Metab Dis 2015 May;38(3):391-403. Epub 2014 Dec 20 doi: 10.1007/s10545-014-9787-3. PMID: 25526709
Robinson BH, MacKay N, Chun K, Ling M
J Inherit Metab Dis 1996;19(4):452-62. doi: 10.1007/BF01799106. PMID: 8884569
Robinson BH, Sherwood WG
J Inherit Metab Dis 1984;7 Suppl 1:69-73. doi: 10.1007/BF03047378. PMID: 6434848

Diagnosis

Karissa P, Simpson T, Dawson SP, Low TY, Tay SH, Nordin FDA, Zain SM, Lee PY, Pung YF
Br J Biomed Sci 2022;79:10382. Epub 2022 May 19 doi: 10.3389/bjbs.2022.10382. PMID: 35996497Free PMC Article
Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB
Orphanet J Rare Dis 2021 Jul 3;16(1):295. doi: 10.1186/s13023-021-01927-w. PMID: 34217336Free PMC Article
Natarajan N, Tully HM, Chapman T
Pediatr Radiol 2016 Aug;46(9):1354-7. Epub 2016 Mar 30 doi: 10.1007/s00247-016-3585-z. PMID: 27026023Free PMC Article
Brown GK, Otero LJ, LeGris M, Brown RM
J Med Genet 1994 Nov;31(11):875-9. doi: 10.1136/jmg.31.11.875. PMID: 7853374Free PMC Article
Robinson BH, Sherwood WG
J Inherit Metab Dis 1984;7 Suppl 1:69-73. doi: 10.1007/BF03047378. PMID: 6434848

Therapy

Karissa P, Simpson T, Dawson SP, Low TY, Tay SH, Nordin FDA, Zain SM, Lee PY, Pung YF
Br J Biomed Sci 2022;79:10382. Epub 2022 May 19 doi: 10.3389/bjbs.2022.10382. PMID: 35996497Free PMC Article
Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB
Orphanet J Rare Dis 2021 Jul 3;16(1):295. doi: 10.1186/s13023-021-01927-w. PMID: 34217336Free PMC Article
Gavrilovici C, Rho JM
J Inherit Metab Dis 2021 Jan;44(1):42-53. Epub 2020 Aug 11 doi: 10.1002/jimd.12283. PMID: 32654164
Stacpoole PW, Owen R, Flotte TR
Curr Gene Ther 2003 Jun;3(3):239-45. doi: 10.2174/1566523034578320. PMID: 12762482
Robinson BH, MacKay N, Chun K, Ling M
J Inherit Metab Dis 1996;19(4):452-62. doi: 10.1007/BF01799106. PMID: 8884569

Prognosis

Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB
Orphanet J Rare Dis 2021 Jul 3;16(1):295. doi: 10.1186/s13023-021-01927-w. PMID: 34217336Free PMC Article
Prasad N, Gottlich C, Nhan D, Hamosh A, Sponseller PD
J Pediatr Orthop 2021 Jul 1;41(6):e457-e463. doi: 10.1097/BPO.0000000000001812. PMID: 34096551
Sofou K, Dahlin M, Hallböök T, Lindefeldt M, Viggedal G, Darin N
J Inherit Metab Dis 2017 Mar;40(2):237-245. Epub 2017 Jan 18 doi: 10.1007/s10545-016-0011-5. PMID: 28101805Free PMC Article
Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW
Mol Genet Metab 2012 Jul;106(3):385-94. doi: 10.1016/j.ymgme.2012.03.017. PMID: 22896851Free PMC Article
Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW
Mol Genet Metab 2012 Jan;105(1):34-43. Epub 2011 Oct 7 doi: 10.1016/j.ymgme.2011.09.032. PMID: 22079328Free PMC Article

Clinical prediction guides

Gokcan H, Bedoyan JK, Isayev O
J Chem Inf Model 2022 Jul 25;62(14):3463-3475. Epub 2022 Jul 7 doi: 10.1021/acs.jcim.2c00630. PMID: 35797142Free PMC Article
Oh J, Koo C, Kim KW, Lee JS
Med Hypotheses 2021 Jan;146:110432. Epub 2020 Dec 1 doi: 10.1016/j.mehy.2020.110432. PMID: 33303308
Castiglioni C, Verrigni D, Okuma C, Diaz A, Alvarez K, Rizza T, Carrozzo R, Bertini E, Miranda M
Eur J Paediatr Neurol 2015 Sep;19(5):497-503. Epub 2015 May 14 doi: 10.1016/j.ejpn.2015.04.008. PMID: 26008863
DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS
Mol Genet Metab 2012 Nov;107(3):394-402. Epub 2012 Sep 7 doi: 10.1016/j.ymgme.2012.09.001. PMID: 23021068
Sheu KF, Hu CW, Utter MF
J Clin Invest 1981 May;67(5):1463-71. doi: 10.1172/jci110176. PMID: 6262377Free PMC Article

Recent systematic reviews

Zweers H, van Wegberg AMJ, Janssen MCH, Wortmann SB
Orphanet J Rare Dis 2021 Jul 3;16(1):295. doi: 10.1186/s13023-021-01927-w. PMID: 34217336Free PMC Article

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