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
Treatment	Low-fat diet Carnitine supplementation Avoidance of fasting, particularly when sick IV glucose during illness
Screening issues	Later-onset variants can occur.