Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare metabolic disorder that affects the body's ability to break down certain fats for energy. It is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated gene (ACADS) — one from each parent — to develop the condition.
Short-chain acyl-CoA dehydrogenase deficiency genetic testing is included in Diagnostiki Athinon Monogenic Diseases Genetic Testing along with approximately 100 other inherited diseases, including cystic fibrosis (71 mutations) and hereditary breast cancer (genes BRCA1 415 mutations & BRCA2 419 mutations).
The key features and aspects of short-chain acyl-CoA dehydrogenase deficiency (SCADD) are:
- Enzyme Deficiency: Short-chain acyl-CoA dehydrogenase deficiency is characterized by a deficiency of the enzyme short-chain acyl-CoA dehydrogenase, which plays a crucial role in the beta-oxidation of fatty acids. This process is essential for converting fats into energy.
- Symptoms: Many individuals with short-chain acyl-CoA dehydrogenase deficiency do not experience any symptoms, and the condition may be identified incidentally through newborn screening or during investigations for other health issues. In some cases, affected individuals may exhibit non-specific symptoms, such as developmental delays, hypotonia (weak muscle tone), and failure to thrive.
- Biochemical Abnormalities: Individuals with short-chain acyl-CoA dehydrogenase deficiency may have elevated levels of certain short-chain fatty acids (butyryl carnitine and ethylmalonic acid) in their blood and urine. Metabolic testing may detect these abnormal levels.
- Genetic Basis: Short-chain acyl-CoA dehydrogenase deficiency is caused by mutations in the ACADS gene, which provides instructions for producing the enzyme. Mutations in this gene result in a less functional enzyme, leading to the biochemical abnormalities observed in individuals with the disease.
- Diagnosis: Diagnosis is often made through newborn screening, which involves testing a small blood sample from a newborn for various metabolic disorders. Confirmation of short-chain acyl-CoA dehydrogenase deficiency may involve additional testing, such as genetic analysis and metabolic studies.
- Treatment: Asymptomatic individuals with short-chain acyl-CoA dehydrogenase deficiency may not require specific treatment. In cases where symptoms are present or concerns about metabolic decompensation during stress (e.g., illness), dietary adjustments and close medical monitoring may be recommended. These adjustments may involve avoiding prolonged fasting and providing a source of carbohydrates during disease.
It's important to note that short-chain acyl-CoA dehydrogenase deficiency is considered a relatively mild disorder compared to some other metabolic conditions. Management strategies are often tailored to the individual's situation, and ongoing medical supervision may be necessary.
Short-chain acyl-CoA dehydrogenase deficiency is due to variants in the ACADS gene encoding for short-chain acyl-CoA dehydrogenase, a key enzyme in mitochondrial fatty acid beta-oxidation. Absence of the enzyme results in the toxic accumulation of butyrylcarnitine (C4-acylcarnitine) and ammonia.
Short-chain acyl-CoA dehydrogenase deficiency was first identified in a compound heterozygous patient for two rare variants in the ACADS gene: c.136C>T and c.319C>T. Subsequently, patients of Ashkenazi Jewish ancestry with c.319C>T were identified. Most patients with symptoms are homozygous for some rare missense or missense variant in ACADS or heterozygous compounds of a rare variant and one of the two common variants c.511C>T and c.625G>A that produce a structurally and catalytically altered form of the enzyme. The common variants c.511C>T and c.625G>A, in isolation and homozygosity, confer some susceptibility to develop SCADD.
Short-chain acyl-CoA dehydrogenase deficiency genetic testing analyzes the 6 most frequent pathogenic mutations of the ACADS gene.
The technique used for genetic testing analyzes only the gene's specific mutations, which are the most important and frequent in the literature. However, it should be noted that there are likely other gene or chromosomal mutations in the gene to be tested that cannot be identified with this method. Different analysis techniques can be used for these cases, such as next-generation sequencing (NGS).
