Pyruvate dehydrogenase E2 deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PDHDD
Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex deficiency
Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex deficiency
Lactic acidemia due to defect of E2 lipoyl transacetylase of the pyruvate dehydrogenase complex
Pyruvate dehydrogenase complex component E2 deficiency
Number of Symptoms 33
OrphanetNr: 79244
OMIM Id: 245348
ICD-10: E74.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
Monogenic
16049940 [IBIS]
Age of onset: Infancy
Childhood
16049940 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Pyruvate dehydrogenase deficiency
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Pyruvate dehydrogenase (PDH) is a multienzyme complex that catalyses the oxidative decarboxylation of pyruvate to yield acetyl CoA. This is an irreversible reaction that links the pathway of glycolysis in the cytoplasm and the citric acid cycle in the mitochondrion. The enzyme is particularly important in the brain in which, under normal conditions, essentially all of the energy is derived from aerobic glucose oxidation. The complex comprises three catalytic components, PDH (E1), dihydrolipoamide acetyltransferase (E2) and dihydrolipoamide dehydrogenase (E3), and two regulatory components, E1 kinase and phospho-E1-phosphatase, together with a sixth component, E3-binding protein, which is believed to play a role in the attachment of E3 to the E2 core (PMID:15138885). Head et al. (2005) describe two unrelated patients with pyruvate dehydrogenase deficiency caused by defects in the E2 (= DLTA, PDC-E2, PDCE2) subunit. Both patients are less severely affected than typical patients with E1alpha mutations (PMID:16049940).

Symptom Information: Sort by abundance 

1
 (HPO:0007738) Uncontrolled eye movements 16049940 IBIS 3 / 7739
2
 (HPO:0000570) Abnormality of saccadic eye movements 16049940 IBIS 12 / 7739
3
 (HPO:0000639) Nystagmus 16049940 IBIS 555 / 7739
4
 (HPO:0000657) Oculomotor apraxia 16049940 IBIS 54 / 7739
5
 (HPO:0000486) Strabismus 16049940 IBIS 576 / 7739
6
 (HPO:0000508) Ptosis 16049940 IBIS 459 / 7739
7
 (HPO:0003128) Lactic acidosis 16049940 IBIS 116 / 7739
8
 (HPO:0004900) Severe lactic acidosis 16049940 IBIS 5 / 7739
9
 (HPO:0002928) Decreased activity of the pyruvate dehydrogenase complex Very frequent [IBIS] 16049940 IBIS 10 / 7739
10
 (HPO:0001266) Choreoathetosis 16049940 IBIS 57 / 7739
11
 (HPO:0003552) Muscle stiffness 16049940 IBIS 23 / 7739
12
 (HPO:0001251) Ataxia 16049940 IBIS 413 / 7739
13
 (HPO:0002311) Incoordination 16049940 IBIS 84 / 7739
14
 (HPO:0001347) Hyperreflexia 16049940 IBIS 363 / 7739
15
 (HPO:0001348) Brisk reflexes 16049940 IBIS 15 / 7739
16
 (HPO:0006801) Hyperactive deep tendon reflexes 16049940 IBIS 21 / 7739
17
 (HPO:0001332) Dystonia 16049940 IBIS 197 / 7739
18
 (HPO:0007325) Generalized dystonia 16049940 IBIS 7 / 7739
19
 (HPO:0002268) Paroxysmal dystonia 16049940 IBIS 11 / 7739
20
 (HPO:0001263) Global developmental delay 16049940 IBIS 853 / 7739
21
 (HPO:0010862) Delayed fine motor development 16049940 IBIS 3 / 7739
22
 (HPO:0002194) Delayed gross motor development 16049940 IBIS 37 / 7739
23
 (HPO:0002307) Drooling 16049940 IBIS 43 / 7739
24
 (HPO:0002465) Poor speech 16049940 IBIS 31 / 7739
25
 (HPO:0006961) Jerky head movements 16049940 IBIS 3 / 7739
26
 (HPO:0001771) Achilles tendon contracture 16049940 IBIS 27 / 7739
27
 (HPO:0001239) Wrist flexion contracture 16049940 IBIS 13 / 7739
28
 (HPO:0000252) Microcephaly 16049940 IBIS 832 / 7739
29
 (HPO:0012751) Abnormal basal ganglia MRI signal intensity 16049940 IBIS 4 / 7739
30
 (HPO:0002453) Abnormality of the globus pallidus 16049940 IBIS 4 / 7739
31
 (MedDRA:10047920) Wheelchair user 16049940 IBIS 3 / 7739
32
 (OMIM) Decreased activity of the E2 subunit (lipoyl transacetylase, 608770) of the PDH 16049940 IBIS 1 / 7739
33
 (OMIM) Decreased levels of the E2 subunit protein 16049940 IBIS 1 / 7739

Associated genes:

DLAT;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Robinson et al. (1990) described a black infant who presented at 2 weeks of age with hyperammonemia and profound lactic acidosis. Control of blood lactates was achieved by carbohydrate restriction and bicarbonate supplementation, but at age 3.5 years ...
Molecular genetics OMIM In 2 unrelated patients with pyruvate dehydrogenase E2 deficiency, Head et al. (2005) identified 2 different homozygous mutations in the DLAT gene (608770.0001 and 608770.0002).