Medium chain acyl-CoA dehydrogenase deficiency

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an “inborn error of metabolism” in which there is an impaired ability to break down medium-chain fatty acids.  In a nutshell, the body can use either glucose (through glycolysis) or fatty acids (through beta-oxidation) to begin producing energy in the mitochondria.  MCAD deficiency affects the body’s ability to efficiently use fatty acids for energy.

MCAD in infants and children:

MCAD deficiency is a fairly rare genetic disorder, and it is usually only diagnosed in children who are homozygous or compound heterozygous for mutations in the A/CADM gene.  Symptoms generally occur when an infant or child hasn’t eaten, often due to being sick with a cold, ear infection, or the flu.  Because the body can’t utilize fatty acids efficiently for energy, children with MCAD deficiency can have problems with hypoglycemia, which can progress to a metabolic crisis. [ref]

Note that not every child that has genetic mutations for MCAD deficiency ends up having problems with MCAD deficiency.  Newborn screenings are now being done to identify infants with MCAD deficiency.  [ref]

Heterozygous mutations:

It is now being recognized that people who are heterozygous for ACADM gene mutations may also have problems with (mild) hypoglycemia during times of intense exercise, fasting, surgery, or illness — basically, times when your body may rely on fatty acids instead of glucose for energy.  Those who are heterozygous may have no problems at all under normal conditions since fatty acid oxidation should still work, just at a less than optimal level.  [ref] [ref] [ref] [ref]

One study sums up with this: “As in other metabolic disorders, the distinction between “normal” and “disease” in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.” [ref]

Check your 23andMe data for the following mutations in the ACADM gene:

Nutrition and lifestyle considerations:

If you are a carrier (heterozygous) for one of the MCAD deficiency mutations, you may find that a higher carb/ lower fat diet may work better for you.  In this era of carbs being demonized, MCAD carriers may need to buck the low carb trend — or at least be alert for signs of hypoglycemia if eating a low carb diet.

For infants and children with MCAD deficiency, carnitine supplementation is sometimes recommended.  Carnitine is an amino acid that is involved in the transport of long-chain fatty acids into the mitochondria for beta-oxidation.  While carnitine is readily available as a supplement (bodybuilders use it), it is also synthesized by the liver and easily found in food sources such as red meat, nuts, and legumes.  Studies of carnitine supplementation for MCADD patients have had mixed results. [ref]

Illegal drugs with synthetic cathinones (sometimes called “bath salts” or “designer drugs”) may prove deadly to someone with MCAD deficiency.  [ref]  So if you need yet another reason not to do drugs, MCADD is one.

More to read:

My Personal Thoughts:  On anything that is a serious genetic disease, please don’t rely on 23andMe data as the only source of testing.  While it is generally accurate, 23andMe data isn’t guaranteed to be totally free of errors.

Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.