Medium chain acyl-CoA dehydrogenase deficiency

Does your blood sugar crash when you don’t eat for a day? Do you find that coconut oil in your coffee doesn’t work well for you? It could be that your body has trouble using medium-chain fatty acids for energy.

What is medium-chain acyl-CoA dehydrogenase deficiency?

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an “inborn error of metabolism” which impairs the body’s ability to break down medium-chain fatty acids for fuel.

In a nutshell, the body can use either glucose (through glycolysis) or fatty acids (through beta-oxidation) as the basis for producing energy in the mitochondria. MCAD deficiency affects the body’s ability to efficiently use medium-chain fatty acids for energy.

MCAD deficiency in infants and children:

MCAD deficiency is a fairly rare genetic disorder, and it is usually only diagnosed in children who carry two copies of mutations in the ACADM gene (some are listed below).

Symptoms of MCADD 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 severe hypoglycemia (low blood sugar), which can progress to a serious metabolic crisis. [ref]

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]

Carrying one copy of an MCADD mutation:

It is now being recognized that people who carry one copy of an ACADM gene mutation may also have problems with hypoglycemia during times of intense exercise, fasting, surgery, or illness — basically, the times when your body may rely only on fatty acids instead of glucose for energy. People with one copy of the mutation 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]


Genetic Variants associated with MCADD:

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The following genetic mutations in the ACADM gene are linked with medium-chain acyl-CoA deficiency. Keep in mind that 23andMe data is not guaranteed to be clinically accurate and false positives are possible. On rare mutations like these, you should always see about getting a second test done through your doctor to confirm any diagnosis.

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

Check your genetic data for rs77931234  (23andMe v4, v5 as i5012759; AncestryDNA):

  • G/G: medium chain acyl-coA dehydrogenase deficiency [ref]
  • A/G: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • A/A: typical

Members: Your genotype for rs77931234 is . If 23andMe, your genotype for i5012759 is .

Check your genetic data for rs121434280 (23andMe v4, v5; AncestryDNA):

  • C/C: medium chain acyl-coA dehydrogenase deficiency[ref]
  • C/T: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • T/T: typical

Members: Your genotype for rs121434280 is .

Check your genetic data for rs373715782 (23andMe v4, v5 i5012760; AncestryDNA):

  • T/T: medium chain acyl-coA dehydrogenase deficiency[ref]
  • C/T: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • C/C: typical

Members: Your genotype for rs373715782 is . If 23andMe, your genotype for i5012760 is .

Check your 23andMe  data for i5012755 (23andMe v4, v5):

  • T/T: medium chain acyl-coA dehydrogenase deficiency
  • C/T: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • C/C: typical

Members: Your genotype for i5012755 is (23andme only).

Check your genetic data for rs121434281 ( 23andMe v4, v5 i5003117; AncestryDNA):

  • T/T: medium chain acyl-coA dehydrogenase deficiency [ref]
  • C/T: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • C/C: typical

Members: Your genotype for rs121434281 is . If 23andMe, your genotype for i5003117 is .

Check your genetic data for rs121434282 ( 23andMe v4, v5; AncestryDNA):

  • C/C: medium chain acyl-coA dehydrogenase deficiency [ref]
  • C/G: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • G/G: typical

Members: Your genotype for rs121434282 is .

Check your genetic data for rs121434277 ( 23andMe v4, v5; AncestryDNA):

  • A/A: medium chain acyl-coA dehydrogenase deficiency [ref]
  • A/G: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • G/G: typical

Members: Your genotype for rs121434277 is .

Check your genetic data for rs121434274( 23andMe v4, v5; AncestryDNA):

  • A/A: medium chain acyl-coA dehydrogenase deficiency [ref]
  • A/G: carrier of one copy of a medium chain acyl-coA dehydrogenase deficiency mutation
  • G/G: typical

Members: Your genotype for rs121434274 is .


Lifehacks:

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.

The key is to keep an eye out for signs of low blood sugar. If you exercise hard, eating before a workout may be beneficial. Anecdotally, drinking a lot of alcohol without eating anything can also cause hypoglycemia for people with one copy of the MCAD mutation.

Blood glucose meters are fairly inexpensive these days. It may be worthwhile to get one and keep track of your blood sugar in times of physiological stress (fasting, illness, pregnancy). This will give you a much better picture of whether or not the MCAD mutation is affecting you.

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, carrying an MCADD mutation is a good one.

More to read:



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. 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 the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.