Format

Send to:

Choose Destination

Pyruvate dehydrogenase E2 deficiency(PDHDD)

MedGen UID:
343386
Concept ID:
C1855565
Disease or Syndrome
Synonyms: Dihydrolipoamide Acetyltransferase (E2) Deficiency; LACTIC ACIDEMIA DUE TO DEFECT OF E2 LIPOYL TRANSACETYLASE OF THE PYRUVATE DEHYDROGENASE COMPLEX; PDHDD
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DLAT (11q23.1)
OMIM®: 245348
Orphanet: ORPHA79244

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 GHR]

Clinical features

Ptosis of eyelid
MedGen UID:
2287
Concept ID:
C0005745
Anatomical Abnormality
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Sign or Symptom
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dribbling from mouth
MedGen UID:
8484
Concept ID:
C0013132
Sign or Symptom
Habitual flow of saliva out of the mouth.
Microcephalus
MedGen UID:
44422
Concept ID:
C0025958
Congenital Abnormality
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
Mild mental retardation (I.Q. 50-70)
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Paroxysmal dystonia
MedGen UID:
97951
Concept ID:
C0393588
Sign or Symptom
A form of dystonia characterized by episodes of dystonia (often hemidystonia or generalized) lasting from minutes to hours. There are no dystonic symptoms between episodes.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Gross motor development delay
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by an delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Jerky head movements
MedGen UID:
383713
Concept ID:
C1855568
Finding
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.
Microcephalus
MedGen UID:
44422
Concept ID:
C0025958
Congenital Abnormality
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
Dribbling from mouth
MedGen UID:
8484
Concept ID:
C0013132
Sign or Symptom
Habitual flow of saliva out of the mouth.
Microcephalus
MedGen UID:
44422
Concept ID:
C0025958
Congenital Abnormality
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Pyruvate dehydrogenase E2 deficiency in Orphanet.

Recent clinical studies

Etiology

Tort F, Ferrer-Cortès X, Thió M, Navarro-Sastre A, Matalonga L, Quintana E, Bujan N, Arias A, García-Villoria J, Acquaviva C, Vianey-Saban C, Artuch R, García-Cazorla À, Briones P, Ribes A
Hum Mol Genet 2014 Apr 1;23(7):1907-15. Epub 2013 Nov 20 doi: 10.1093/hmg/ddt585. [Epub ahead of print] PMID: 24256811

Diagnosis

Ferdinandusse S, Friederich MW, Burlina A, Ruiter JP, Coughlin CR 2nd, Dishop MK, Gallagher RC, Bedoyan JK, Vaz FM, Waterham HR, Gowan K, Chatfield K, Bloom K, Bennett MJ, Elpeleg O, Van Hove JL, Wanders RJ
Orphanet J Rare Dis 2015 Jun 18;10:79. doi: 10.1186/s13023-015-0290-1. [Epub ahead of print] PMID: 26081110Free PMC Article
Soreze Y, Boutron A, Habarou F, Barnerias C, Nonnenmacher L, Delpech H, Mamoune A, Chrétien D, Hubert L, Bole-Feysot C, Nitschke P, Correia I, Sardet C, Boddaert N, Hamel Y, Delahodde A, Ottolenghi C, de Lonlay P
Orphanet J Rare Dis 2013 Dec 17;8:192. doi: 10.1186/1750-1172-8-192. [Epub ahead of print] PMID: 24341803Free PMC Article
McWilliam CA, Ridout CK, Brown RM, McWilliam RC, Tolmie J, Brown GK
Eur J Paediatr Neurol 2010 Jul;14(4):349-53. Epub 2009 Dec 21 doi: 10.1016/j.ejpn.2009.11.001. [Epub ahead of print] PMID: 20022530
Okajima K, Korotchkina LG, Prasad C, Rupar T, Phillips JA 3rd, Ficicioglu C, Hertecant J, Patel MS, Kerr DS
Mol Genet Metab 2008 Apr;93(4):371-80. Epub 2008 Mar 4 doi: 10.1016/j.ymgme.2007.10.135. [Epub ahead of print] PMID: 18164639
Lib MY, Brown RM, Brown GK, Marusich MF, Capaldi RA
J Histochem Cytochem 2002 Jul;50(7):877-84. PMID: 12070266

Therapy

Taylor MR, Hurley JB, Van Epps HA, Brockerhoff SE
Proc Natl Acad Sci U S A 2004 Mar 30;101(13):4584-9. Epub 2004 Mar 15 doi: 10.1073/pnas.0307074101. [Epub ahead of print] PMID: 15070761Free PMC Article

Prognosis

Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW
Mol Genet Metab 2012 Jul;106(3):385-94. 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. [Epub ahead of print] PMID: 22079328Free PMC Article
Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M
Mol Genet Metab 2011 Dec;104(4):507-16. Epub 2011 Aug 18 doi: 10.1016/j.ymgme.2011.08.008. [Epub ahead of print] PMID: 21914562
Okajima K, Korotchkina LG, Prasad C, Rupar T, Phillips JA 3rd, Ficicioglu C, Hertecant J, Patel MS, Kerr DS
Mol Genet Metab 2008 Apr;93(4):371-80. Epub 2008 Mar 4 doi: 10.1016/j.ymgme.2007.10.135. [Epub ahead of print] PMID: 18164639
Odièvre MH, Chretien D, Munnich A, Robinson BH, Dumoulin R, Masmoudi S, Kadhom N, Rötig A, Rustin P, Bonnefont JP
Hum Mutat 2005 Mar;25(3):323-4. doi: 10.1002/humu.9319. PMID: 15712224

Clinical prediction guides

Imbard A, Boutron A, Vequaud C, Zater M, de Lonlay P, de Baulny HO, Barnerias C, Miné M, Marsac C, Saudubray JM, Brivet M
Mol Genet Metab 2011 Dec;104(4):507-16. Epub 2011 Aug 18 doi: 10.1016/j.ymgme.2011.08.008. [Epub ahead of print] PMID: 21914562
Okajima K, Korotchkina LG, Prasad C, Rupar T, Phillips JA 3rd, Ficicioglu C, Hertecant J, Patel MS, Kerr DS
Mol Genet Metab 2008 Apr;93(4):371-80. Epub 2008 Mar 4 doi: 10.1016/j.ymgme.2007.10.135. [Epub ahead of print] PMID: 18164639
Odièvre MH, Chretien D, Munnich A, Robinson BH, Dumoulin R, Masmoudi S, Kadhom N, Rötig A, Rustin P, Bonnefont JP
Hum Mutat 2005 Mar;25(3):323-4. doi: 10.1002/humu.9319. PMID: 15712224
Wilichowski E, Korenke GC, Ruitenbeek W, De Meirleir L, Hagendorff A, Janssen AJ, Lissens W, Hanefeld F
J Neurol Sci 1998 May 7;157(2):206-13. PMID: 9619647
Robinson BH, MacKay N, Petrova-Benedict R, Ozalp I, Coskun T, Stacpoole PW
J Clin Invest 1990 Jun;85(6):1821-4. doi: 10.1172/JCI114641. PMID: 2112155Free PMC Article

Recent systematic reviews

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. [Epub ahead of print] PMID: 22079328Free PMC Article

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...