Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

About the condition MCAD deficiency is a fatty acid oxidation disorder. It is a hereditary disease that is caused by a missing enzyme needed to convert fat into energy. Children with MCAD deficiency therefore cannot fast for very long without developing hypoglycaemia, which can cause brain damage or even death.
Inheritance Autosomal recessive
Year screening started in WA 2005
Incidence in WA 1 in 12,000 births. MCAD deficiency is more common in persons of a Northern European background, but it does also occur in other populations.
Enzyme defect Deficiency of medium-chain acyl-CoA dehydrogenase; an enzyme that participates in fatty acid oxidation.
Symptoms if untreated MCAD deficiency typically causes problems in infancy or early childhood. The children are usually well until they develop another illness such as gastroenteritis, which stops them from feeding. They then develop hypoglycaemia associated with lethargy, hepatomegaly, seizures, coma and death. About 1 in 4 children with MCAD deficiency will die from their first crisis so it is important to diagnose and treat these children early. Some children may never have symptoms.
Metabolites on bloodspot screening
  • Increased medium-chain acylcarnitines (C6, C8, C10, C10:1)
  • Increased C8/C2 ratio
Diagnostic tests
  • Plasma acylcarnitine profile
  • Urine organic acids
  • ACADM gene analysis
  • Low-fat diet
  • Carnitine supplementation
  • Avoidance of fasting, particularly when sick
  • IV glucose during illness
Screening issues Later-onset variants can occur.