Short-chain acyl-CoA dehydrogenase

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a rare genetic disorder of fatty acid metabolism that is autosomal recessively inherited. It is characterized by a deficiency in the enzyme short-chain acyl-CoA dehydrogenase, which is crucial for the metabolic pathway that converts short-chain fatty acids into energy. This condition can lead to a variety of symptoms, including hypoglycemia, muscle weakness, and developmental delays. Early diagnosis and management are key to improving outcomes for affected individuals.

Symptoms and Signs[edit | edit source]

The clinical presentation of SCAD deficiency can vary widely among affected individuals. Common symptoms include:

Hypoglycemia: Low blood sugar levels, especially during periods of fasting or illness.
Muscle weakness: Reduced muscle tone and strength.
Developmental delays: Slower than normal development of motor skills and cognitive abilities.
Failure to thrive: Difficulty gaining weight and growing at the expected rate.
Metabolic acidosis: A condition where the body produces too much acid, or the kidneys are not removing enough acid from the body.

Causes[edit | edit source]

SCAD deficiency is caused by mutations in the ACADS gene, which provides instructions for making the short-chain acyl-CoA dehydrogenase enzyme. This enzyme plays a critical role in the mitochondrial oxidation of short-chain fatty acids, a process that converts fats into energy. Mutations in the ACADS gene reduce or eliminate the activity of this enzyme, leading to the accumulation of fatty acids and their metabolites in the body, which can disrupt normal metabolic processes.

Diagnosis[edit | edit source]

Diagnosis of SCAD deficiency typically involves a combination of clinical evaluation, family history, and laboratory testing. Key diagnostic tests include:

Blood tests: To measure the levels of acylcarnitines, which can be elevated in SCAD deficiency.
Urine tests: To detect the presence of abnormal organic acids.
Genetic testing: To identify mutations in the ACADS gene.
Enzyme activity assay: To measure the activity of the short-chain acyl-CoA dehydrogenase enzyme in cultured skin fibroblasts or muscle tissue.

Treatment[edit | edit source]

There is no cure for SCAD deficiency, but treatment focuses on managing symptoms and preventing metabolic crises. Treatment strategies may include:

Dietary management: A diet low in fat and rich in carbohydrates to minimize the intake of short-chain fatty acids.
Carnitine supplementation: To help in the removal of excess fatty acids from the body.
Avoidance of fasting: To prevent hypoglycemia.
Prompt treatment of illnesses: To prevent metabolic decompensation during periods of increased energy demand.

Prognosis[edit | edit source]

The prognosis for individuals with SCAD deficiency varies. Some individuals may remain asymptomatic or develop only mild symptoms, while others may experience more severe complications. Early diagnosis and appropriate management can significantly improve the quality of life and reduce the risk of serious complications.