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Pyruvate dehydrogenase E1-beta deficiency(PDHBD)

MedGen UID:
481471
Concept ID:
C3279841
Disease or Syndrome
Synonym: PDHBD
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
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).
 
Gene (location): PDHB (3p14.3)
 
Monarch Initiative: MONDO:0013580
OMIM®: 614111
Orphanet: ORPHA255138

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]

Clinical features

From HPO
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
Metabolic acidosis characterized by the accumulation of lactate in the body. It is caused by tissue hypoxia.
Hyperammonemia
MedGen UID:
113136
Concept ID:
C0220994
Disease or Syndrome
An increased concentration of ammonia in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Pyruvate dehydrogenase E1-beta deficiency in Orphanet.

Recent clinical studies

Diagnosis

Prasad C, Rupar T, Prasad AN
Brain Dev 2011 Nov;33(10):856-65. Epub 2011 Sep 9 doi: 10.1016/j.braindev.2011.08.003. PMID: 21908116
Quintana E, Mayr JA, García Silva MT, Font A, Tortoledo MA, Moliner S, Ozaez L, Lluch M, Cabello A, Ricoy JR, Koch J, Ribes A, Sperl W, Briones P
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S339-43. Epub 2009 Nov 9 doi: 10.1007/s10545-009-1343-1. PMID: 19924563
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. PMID: 18164639
Chun K, MacKay N, Petrova-Benedict R, Robinson BH
Am J Hum Genet 1991 Aug;49(2):414-20. PMID: 1907799Free PMC Article
Old SE, De Vivo DC
Ann Neurol 1989 Dec;26(6):746-51. doi: 10.1002/ana.410260610. PMID: 2513771

Prognosis

Quintana E, Mayr JA, García Silva MT, Font A, Tortoledo MA, Moliner S, Ozaez L, Lluch M, Cabello A, Ricoy JR, Koch J, Ribes A, Sperl W, Briones P
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S339-43. Epub 2009 Nov 9 doi: 10.1007/s10545-009-1343-1. PMID: 19924563
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. PMID: 18164639
Seyda A, McEachern G, Haas R, Robinson BH
Hum Mol Genet 2000 Apr 12;9(7):1041-8. doi: 10.1093/hmg/9.7.1041. PMID: 10767328
Chun K, MacKay N, Petrova-Benedict R, Robinson BH
Hum Mol Genet 1993 Apr;2(4):449-54. doi: 10.1093/hmg/2.4.449. PMID: 8504306

Clinical prediction guides

Quintana E, Mayr JA, García Silva MT, Font A, Tortoledo MA, Moliner S, Ozaez L, Lluch M, Cabello A, Ricoy JR, Koch J, Ribes A, Sperl W, Briones P
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S339-43. Epub 2009 Nov 9 doi: 10.1007/s10545-009-1343-1. PMID: 19924563
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. PMID: 18164639
Chun K, MacKay N, Petrova-Benedict R, Robinson BH
Am J Hum Genet 1991 Aug;49(2):414-20. PMID: 1907799Free PMC Article

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