Pyruvate dehydrogenase E1-beta deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PDHBD
Pyruvate dehydrogenase complex E1 component subunit beta deficiency
Number of Symptoms 13
OrphanetNr: 255138
OMIM Id: 614111
ICD-10: E74.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
15138885 [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. The E1 enzyme is a heterotetramer of two E1 alpha subunits and two E1 beta subunits with thiamine pyrophosphate as a cofactor. The cofactor binding and catalytic sites are formed at the interface of the alpha and beta subunits. PDH deficiency is a well defined biochemical defect that is clinically highly heterogeneous. It is one of the major causes of severe primary lactic acidosis in the newborn period and infancy but can also present as a more chronic neurodegenerative disease with extensive cerebral atrophy and structural anomalies in the brain, as Leigh syndrome or as episodic ataxia. In Brown et al. (2004) two unrelated patients with PDH deficiency attributable to missense mutations in PDHB (= PDHBD, PDHE1-B, PHE1B) are described. Both patients presented with lactic acidosis and neurological dysfunction and had little residual PDH activity in cultured fibroblasts (PMID:15138885).

Symptom Information: Sort by abundance 

1
(HPO:0001522) Death in infancy 15138885 IBIS 275 / 7739
2
(OMIM) Respiratory stridor in infancy 15138885 IBIS 2 / 7739
3
(HPO:0005943) Respiratory arrest 15138885 IBIS 5 / 7739
4
(HPO:0001612) Weak cry 15138885 IBIS 17 / 7739
5
(HPO:0001265) Hyporeflexia 15138885 IBIS 208 / 7739
6
(HPO:0001274) Agenesis of corpus callosum 15138885 IBIS 142 / 7739
7
(HPO:0001987) Hyperammonemia 15138885 IBIS 50 / 7739
8
(HPO:0002151) Increased serum lactate 15138885 IBIS 92 / 7739
9
(HPO:0001942) Metabolic acidosis 15138885 IBIS 81 / 7739
10
(HPO:0002928) Decreased activity of the pyruvate dehydrogenase complex Very frequent [IBIS] 15138885 IBIS 10 / 7739
11
(HPO:0000707) Abnormality of the nervous system Very frequent [IBIS] 15138885 IBIS 61 / 7739
12
(HPO:0003128) Lactic acidosis Very frequent [IBIS] 15138885 IBIS 116 / 7739
13
(HPO:0001290) Generalized hypotonia 15138885 IBIS 51 / 7739

Associated genes:

PDHB;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Brown et al. (2004) reported 2 unrelated patients with pyruvate dehydrogenase deficiency. The first patient, the son of first-cousin parents, was investigated at age 3 months because of lactic acidosis and hypotonia. Two previous sibs had died early, ...
Molecular genetics OMIM In 2 unrelated patients with pyruvate dehydrogenase deficiency, Brown et al. (2004) identified homozygous mutations in the PDHB gene (179060.0001-179060.0002).