This report describes pyruvate dehydrogenase E1-beta deficiency (PDHB), which is a subtype of pyruvate dehydrogenase complex deficiency; PDHB exhibits autosomal recessive inheritance. The human gene implicated in this disease, also designated PDHB, encodes a subunit of pyruvate dehydrogenase complex, a mitochondrial multi-enzyme complex that catalyzes the entry point of pyruvate into the TCA cycle. There is a single orthologous gene in Drosophila, Dmel\Pdhb, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated.
The human PDHB gene has not been introduced into flies.
In order to isolate neural effects, neuron-specific knockdown of Dmel\Pdhb, effected by RNAi, has been characterized. Pan-neuronal knockdown of Pdhb induces locomotor defects in both larval and adult stages, abnormal morphology of the motor neuron terminals at neuromuscular junctions, mitochondrial fragmentation in the brain, and shortened lifespan. Physical interactions of Dmel\Pdhb have been described; see below and in the Pdhb gene report.
[updated Feb. 2019 by FlyBase; FBrf0222196]
Pyruvate dehydrogenase deficiency is characterized by the buildup of lactic acid in the body and a variety of neurological problems. 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. In addition to lactic acidosis, the production of cellular energy is diminished. The brain, which requires especially large amounts of energy, is severely affected, resulting in neurological problems. 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 Genetics Home Reference, Pyruvate dehydrogenase deficiency; 2019.02.20]
Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987, pubmed:3116190; Brown et al., 1994, pubmed:7853374). [from MIM:312170; 2019.02.20]
[PYRUVATE DEHYDROGENASE E1-BETA DEFICIENCY; PDHBD](https://omim.org/entry/614111)
[PYRUVATE DEHYDROGENASE E1, SUBUNIT BETA; PDHB](https://omim.org/entry/179060)
Severe forms of pyruvate dehydrogenase deficiency have been mapped to the PDHB gene. As infants, the patients exhibited lactic acidosis and hypotonia, with respiratory crises and poor prognosis (Brown et al., 2004; pubmed:15138885). [from MIM:614111; 2019.02.20]
Pyruvate dehydrogenase E1-beta deficiency is caused by homozygous mutation in the PDHB gene. [from MIM:614111; 2019.02.20]
The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 beta subunit. [NCBI Gene: PDHB; 2019.02.20]
One to one: 1 human to 1 Drosophila
High-scoring ortholog of human PDHB (1 Drosophila to 1 human). Dmel\Pdhb shares 67% identity and 81% similarity with the human gene.
