About MCAD Deficiency

What is MCAD deficiency?

Your body needs energy to function properly. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) is a genetic disease that affects your body's ability to break down certain fats and convert them into energy. When this process doesn't work properly, the level of sugar in your blood can become dangerously low.

Although MCAD deficiency is present from birth, a person affected with MCAD deficiency does not usually show signs of it until they can't make adequate energy. This might occur when the person goes without food for an extended period of time (such as when a baby is weaned from nighttime feedings or when a person fasts for a surgical procedure) or when their body is stressed by a fever or gastrointestinal illness.

Unfortunately, if not treated, this first episode of energy deficiency can quickly lead to death or severe organ damage. That's why all newborns born in the United States (and many other countries) are tested for MCAD deficiency at birth.

What gene is associated with MCAD deficiency?

MCAD deficiency is an inherited genetic disease caused by variants in the ACADM gene located on chromosome 1.

The ACADM gene instructs the cell to make the medium-chain acyl-CoA dehydrogenase (MCAD) enzyme, which breaks down fat molecules into smaller pieces for energy production.

What does it mean to be a carrier of MCAD deficiency?

A carrier is someone who "carries" one variant in a gene, but it doesn't cause them any ill health effects. While MCAD deficiency carriers do not have the disease, they can pass on that gene variant to their children.

In the United States, about 1 in 63 people of non-Hispanic White ethnicity are carriers for genetic variants in the ACADM gene.

How do you pass an ACADM variant?

https://www.mayoclinic.org//-/media/kcms/gbs/patient-consumer/images/2017/08/30/16/56/autosomal_recessive-1.png A person who is a carrier of an autosomal recessive condition has a 50 percent (1 in 2) chance of passing the variant to each of his or her children. https://www.mayoclinic.org//-/media/kcms/gbs/patient-consumer/images/2017/08/30/16/59/autosomal_recessive-2.png If both parents are carriers, the likelihood of the child becoming a carrier is still 50 percent (1 in 2). However, there is a 25 percent (1 in 4) chance that a child could be affected with the disease.

MCAD Enzyme

How the MCAD enzyme work in the body:

Your body gets energy first by burning sugar (glucose) in the blood and then by using the stored sugar in the liver and muscle cells. Once all the sugar is used up, the body starts breaking down fats (called fatty acid oxidation). Fatty acid oxidation requires several enzymes, including MCAD, to break down fats into smaller and smaller pieces.

When a person has two ACADM gene variants, the MCAD enzyme cannot be made appropriately. This leads to the inability to break down fats completely. As long as a person affected with MCAD deficiency has enough glucose in his or her body, the body will not be as dependent on fatty acid oxidation for energy and will not get worse during a crisis.