Mutations of the ACADS gene are associated with deficiency of the short-chain acyl-coenzyme A dehydrogenase protein (SCADD); this is also known as butyryl-CoA dehydrogenase deficiency. Many mutations have been identified in specific populations, and large-scale studies have been performed to determine the allelic and genotypic frequency for the defective gene.[12][13] As short-chain acyl-CoA dehydrogenase is involved in beta-oxidation, a deficiency in this enzyme is marked by an increased amount of fatty acids. This deficiency is characterized by the presence of increased butyrylcarnitine (C4) in blood plasma, and increased ethylmalonic acid (EMA) concentrations in urine. Genotypes of individuals with this deficiency have it as a result of a mutation, variant, or a combination of the two.[14] Among one population with the disease, three subgroups have been identified: one group has a failure to thrive, feeding difficulties, and hypotonia; another group had seizures; finally, one group had hypotonia and no seizures.[15] Other studies showed that the deficiency may be asymptomatic in some individuals under normal conditions, with symptoms presenting under physiological stress conditions such as fasting or illness.[16] The treatment of this deficiency can sometimes be unclear, because it can sometimes be asymptomatic. The treatment for this disease is similar to treatment of other fatty acid oxidation disorders, by trying to restore biochemical and physiologic homeostasis, by promoting anabolism and providing alternative sources of energy.
[14] Flavin adenine dinucleotide supplementation has also been identified as a therapy for this deficiency, because it is an essential cofactor for proper function of SCAD.[17] SCAD deficiency is inherited in an autosomal recessive manner. Carrier testing can be performed for at-risk family members, and prenatal testing is also a possibility.
[14]
The ACADS gene has also been implicated in delaying the onset of Prader-Willi Syndrome, which is characterized by hypotonia, growth failure, and neurodevelopmental delays in the first years of life, and hyperphagia and obesity much later.[18]
In a genome-wide association study (GWAS), a single-nucleotide polymorphism in ACADS has been associated with a reduced amount of insulin release shown by an oral glucose tolerance test, or OGTT.[19]
