This report describes mitochondrial ECHS1 deficiency (mitochondrial short-chain enoyl-CoA hydratase 1 deficiency; ECHS1D). ECHS1D exhibits autosomal recessive inheritance. The human gene implicated, ECHS1, encodes a protein that functions in the mitochondrial fatty acid beta-oxidation pathway; it also plays a role in leucine, isoleucine and valine catabolism. There is a single orthologous gene in Drosophila, Echs1, for which a number of genetic reagents have been generated including a null allele, RNAi-targeting constructs and overexpression contructs.
Multiple UAS constructs of human Hsap\ECHS1 have been introduced into flies, including wild-type and a variant implicated in ECHS1D; see the 'Disease-Implicated Variants' table below. Partial heterologous rescue (functional complementation) has been demonstrated for the larval lethality phenotype of a Dmel\Echs1 amorphic mutation.
Animals homozygous for a null mutation of Dmel\Echs1 die during the larval stage, typically during the second larval instar. First instar larvae exhibit locomotor impairment. Metabolites linked to ECHS1D pathogenesis in humans are be highly elevated in Dmel\Echs1 null animals. Dietary restriction of valine was tested in this model: Echs1-null larvae fed diets with reduced valine content exhibit significant extensions to survival; however, wild-type larvae fed the same diets exhibit reduced rates of survival to the pupal stage.
[updated June 2025 by FlyBase; FBrf0222196]
[MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY; ECHS1D](https://omim.org/entry/616277)
[ENOYL-CoA HYDRATASE, SHORT-CHAIN, 1, MITOCHONDRIAL; ECHS1](https://omim.org/entry/602292)
Mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, brain lesions in the basal ganglia, and dystonia (summary by Peters et al., 2014; pubmed:25125611). [from MIM:616277; 2025.03.25]
ECHS1D) is caused by homozygous or compound heterozygous mutation in the ECHS1 gene. [from MIM:616277; 2025.03.25]
ECHS1 encodes a protein that localizes to the mitochondrial matrix and functions in the second step of the mitochondrial fatty acid beta-oxidation pathway. It also plays a role in metabolism of leucine, isoleucine and valine (branched-chain amino acids). [from GeneCards, ECHS1; 2025.03.25]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human ECHS1 (1 Drosophila to 1 human).
