ACADVL gene

The ACADVL gene (ACADVL stands for: Acyl-CoA Dehydrogenase Very Long Chain) is a protein-coding gene located on chromosome 17p13.1. Alternative splicing leads to multiple transcript variants encoding different isoforms. Associated signaling pathways include the unfolded protein response (UPR) and fatty acid metabolism.

The very long-chain specific acyl-CoA dehydrogenase is one of the acyl-CoA dehydrogenases that catalyze the first step of mitochondrial fatty acid beta-oxidation, an aerobic process in which fatty acids are degraded to acetyl-CoA, enabling energy production from fats.

The protein encoded by this gene, acyl-CoA dehydrogenase very long chain, is a dehydrogenase localized in the inner mitochondrial membrane. Here, the enzyme catalyzes the first step of the mitochondrial fatty acid beta-oxidation pathway. This acyl-coenzyme A dehydrogenase is specific for long-chain and very long-chain fatty acids. Deficiency of this gene product reduces myocardial fatty acid beta-oxidation and is associated with cardiomyopathy.

Diseases associated with ACADVL include:

• Acyl-Coa Dehydrogenase, Very Long-Chain, Deficiency Of and Intellectual Developmental Disorder, Autosomal Dominant (ICD10 E71.3). Synonyms are: MCID: ACY010; Very Long-Chain Acyl-Coenzyme a Dehydrogenase Deficiency; Very Long Chain Acyl-Coa Dehydrogenase; Vlcad-C; Acadvl; MeSH:D008052; OMIM: 201475. Def: Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited metabolic disorder that impairs mitochondrial oxidation of long chain fatty acids, resulting in an inability to convert certain fats into energy, particularly during fasting. This disease is clinically heterogeneous and occurs in three main forms, depending on the age of onset and severity of symptoms. The severe early form manifests in infancy with symptoms such as lethargy, muscle weakness, hypoglycemia, liver abnormalities and life-threatening heart problems with a high incidence of cardiomyopathy and mortality. The childhood-onset form typically presents with hypoketotic hypoglycemia, hepatomegaly and other liver problems, but has a more favorable course and lower mortality compared to the early-onset form. The juvenile or adult-onset form is characterized by exercise- or fasting-induced rhabdomyolysis, myoglobinuria with red or brown urine, and isolated skeletal muscle involvement without significant cardiomyopathy.

1. Miller MJ et al. (2015) Recurrent ACADVL molecular findings in individuals with a positive newborn screen for very long chain acyl-coA dehydrogenase (VLCAD) deficiency in the United States. Mol Genet Metab 116:139-145.
2. Arunath V et al. (2021) A novel mutation in ACADVL causing very long-chain acyl-coenzyme-A dehydrogenase deficiency in a South Asian pediatric patient: a case report and review of the literature. J Med Case Rep 15(1):441.
3. Li X et al. (2015) Very long-chain acyl-coenzyme A dehydrogenase deficiency in Chinese patients: eight case reports, including one case of prenatal diagnosis. Eur J Med Genet 58:134-139.