This report describes hypervalinemia and hyperleucine-isoleucinemia, an inheritated amino acid metabolic disorder. The human gene implicated is BCAT2, which encodes branched chain amino acid transaminase 2, functional comment. There is one high-scoring fly ortholog, Dmel\Bcat, for which multiple genetic reagents, including a loss of function allele, classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Wild-type Hsap\BCAT2 has been introduced into flies, but has not been used to model disease; partial heterologous rescue (functional complementation) of the loss of function Dmel\Bcat semilethal phenotype has been demonstrated.
A Dmel\Bcat allele that produces a truncated protein product results in a 4% adult survival rate; transgenic expression of Hsap\BCAT2 results in a 60% survival rate. Treatment with a diet in which the concetration of branched-chain amino acids (Leu, Ile, Val) was reduced by 50% resulted in a 34% survival rate, while a dietary reduction in one or two BCAAs did not affect the survival rate.
[updated Sept. 2024 by FlyBase; FBrf0222196]
[HYPERVALINEMIA AND HYPERLEUCINE-ISOLEUCINEMIA; HVLI](https://omim.org/entry/618850)
[BRANCHED-CHAIN AMINOTRANSFERASE 2; BCAT2](https://omim.org/entry/113530)
Hypervalinemia and hyperleucine-isoleucinemia is associated with developmental delay, intellectual disability, seizures, and movement defects (Knerr, et al., 2019, pubmed:31177572).
Hypervalinemia and hyperleucine-isoleucinemia (HVLI) is a branched-chain amino acid metabolic disorder characterized by highly elevated plasma valine and leucine concentrations. [from MIM:618850; 2024.09.05]
Hypervalinemia and hyperleucine-isoleucinemia (HVLI) is caused by compound heterozygous mutation in the BCAT2 gene on chromosome 19q13. [from MIM:618850; 2024.09.09]
The BCAT2 gene encodes the mitochondrial isoform of the branched-chain amino acid (BCAA) aminotransferase (BCAT), which catalyzes the transamination of the branched-chain amino acids (leucine, isoleucine, and valine) to their respective alpha-keto acids in the first step of BCAA catabolism (summary by Wang et al., 2015, pubmed:25653144). [from MIM:113530; 2024.09.09]
Two to one (2 human to 1 Drosophila); BCAT2 has one high-scoring Drosophila ortholog, Bcat.
High-scoring ortholog of human BCAT1 and BCAT2 (1 Drosophila to 2 human).
