This report describes multiple acyl-CoA dehydrogenase deficiency, ETFDH-related, previously called glutaric acidemia IIC; MADD, ETFDH-related exhibits an autosomal recessive pattern of inheritance. The human gene electron transfer flavoprotein dehydrogenase (ETFDH) is one of three genes identified as implicated in MADD; all three are subunits of or interact with electron transfer flavoprotein and are involved in electron transfer in the mitochondrial respiratory chain. There is a single ortholog of ETFDH in Drosophila, Etf-QO, for which classical loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human ETFDH gene has not been introduced into flies.
When homozygous, loss-of-function mutations of Dmel\Etf-QO are lethal during the embryonic stage; accumulation of acylcarnitines is observed in the homozygous embryos. High levels of plasma acylcarnitines is a diagnostic characteristic of MADD and several other related diseases.
[updated Jun. 2017 by FlyBase; FBrf0222196]
Clinical features of patients with MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. [from MIM:231680; 2017.05.31]
Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid and amino acid oxidation; it is a clinically heterogeneous disorder ranging from a severe neonatal presentation with metabolic acidosis, cardiomyopathy and liver disease, to a mild childhood/adult disease with episodic metabolic decompensation, muscle weakness, and respiratory failure (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=26791).
See general description of MADD, above.
ETFDH (electron transfer flavoprotein dehydrogenase) is a component of the electron-transfer system in mitochondria; it is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. (Gene Cards, ETFDH; 2017.06.01)
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human ETFDH (1 Drosophila to 1 human); Dmel\Etf-QO shares 66% identity and 80% similarity with the human gene.
