Fatty Acid Molecules (Creative Commons Wikimedia)

Fatty Acid Molecules (Creative Commons Wikimedia)

If you have tried fasting or a ketogenic diet and felt really horrible, this article may apply to you.

The human body is wonderfully made and resilient enough to get energy from either carbs or fats — for most people.  But there are certain genetic mutations that can cause people not to burn fat for energy as efficiently.

Short Chain Acyl-CoA Dehydrogenase Deficiency (SCADD) is a disorder of fatty acid oxidation and mitochondrial energy production.  Think back to high school biology class when you learned that the mitochondria are the cellular “powerhouse”, making ATP or energy for our body.  That process of ATP production can begin with either glucose (a sugar) or fatty acids.  Glycolysis breaks down the glucose into two pyruvate molecules, which are then transformed into acetyl-CoA.  Fatty acids also can be used to create acetyl-CoA, which begins the Kreb’s cycle and the rest of mitochondrial energy production.

Short Chain Acyl-CoA Dehydrogenase is an enzyme that converts short-chain fatty acids for use in the Kreb’s cycle, and a deficiency of the enzyme makes it harder for an individual to use certain fatty acids for fuel.

SCADD is a type of inborn error of metabolism (inherited disorders that affect a person’s ability to metabolize various foods or substances).  Most of these disorders are inherited in an “autosomal recessive” manner, meaning that a person needs to have two recessive alleles to have the disease.


ACADS Genetic variants:

Mutations in the ACADS gene are the cause of short-chain acyl-CoA dehydrogenase deficiency.  Those listed below are available in 23andMe data.

Check your 23andMe data for rs1800556 (v4, v5),  c.511C>T

  • TT:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency [ref]
  • CT: carrier (heterozygous) of SCAD deficiency allele
  • CC: normal

 

Check your 23andMe data for rs28940874 (v4, v5)  c.575C>T

  • TT:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • CT: carrier (heterozygous) of SCAD deficiency allele
  • CC: normal

 

Check your 23andMe data for rs61732144 (v4, v5) c.319C>T

  • TT:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • CT: carrier (heterozygous) of SCAD deficiency allele
  • CC: normal

 

Check your 23andMe data for rs28941773 (v4,v5) c.1058C>T

  • TT:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • CT: carrier (heterozygous) of SCAD deficiency allele
  • CC: normal

 

Check your 23andMe data for rs28940872 (v4, v5) c.1147C>T

  • TT:  pathogenic for short-chain acyl-CoA dehydrogenase deficiency[ref]
  • CT: carrier (heterozygous) of SCAD deficiency allele
  • CC: normal

i5007491 (v4 only)  rs121908005 -The A allele is listed as pathogenic for SCADD[ref]

i5007492 (v4 only) rs121908006 -The T allele is listed as pathogenic for SCADD[ref]

i5007490 (v4 only)  rs1799958 – This one is a more common variant; it is thought that the A allele adds to susceptibility to SCADD when combined with other ACADS polymorphisms.  [ref]

SCAD deficiency – more information and studies

Infants diagnosed with SCADD have symptoms that can include hypoglycemia, lack of energy, vomiting, poor feeding, seizures, poor muscle tone, developmental delays and failure to grow/thrive.

Some newborn screenings now look for SCADD.  Increased screening has led to now understanding that a lot of infants who carry the pathogenic alleles do not have major SCADD symptoms and no treatment is needed.

Affected individuals may only have symptoms during times of fasting, illness, or other physiologic stress.  This makes sense when you look at how glycolysis and fatty acid oxidation works within our body.  Those who are carriers (heterozygous) for a pathogenic allele along with other polymorphisms in ACADS may also have symptoms when their bodies are stressed.  Studies so far have been small and inconclusive. [ref]  Recommendation for children with SCADD is to make sure they eat regularly to prevent hypoglycemia.


Lifehacks

Fasting: For those who are heterozygous (one copy) for one of the pathogenic variants listed above,  be aware that in times of fasting or illness, you may not be able to function as well as others can.  This may be especially true for kids.

No ketogenic or low carb diet:
I know for myself (heterozygous for one of the variants), I felt really terrible and fatigued when trying a low carb diet.

Mouse studies show that a low-fat diet (or a ‘not high-fat diet’) may be helpful.  One study found a decrease in mitochondrial energy with a high-fat diet.  Another mouse study from 2012 found that ACADS deficient mice on a high-fat diet had a state of energy deficiency in the brain. A proteomics (protein) study found that 13 mitochondrial proteins had altered levels in individuals with ACADS mutations.

Supplements:
FAD (flavin adenine dinucleotide) is essential for SCAD function as well as other steps in the production of energy is the mitochondria.  FAD is produced in the body from riboflavin (vitamin B2), thus riboflavin is sometimes supplemented in those who have SCADD. [ref] [ref]

Riboflavin supplements may be worth trying if you don’t think you get enough via your diet. The active form of riboflavin is called riboflavin 5′ phosphate. You can also get powdered riboflavin from Bulk Supplements if you don’t want any added excipients in your supplement.

More to Read:

Medium Chain Acyl-CoA Dehydrogenase Deficiency


3 Comments

Liz Pacosa · July 7, 2018 at 5:19 pm

Debbie, could not find any i500 genes tested on 23nMe. The two ACADS listed in my raw data were ok.
*Many other ACADS variants are listed that you don’t mention.
(The raw data links to ncbi weren’t helpful, unfortunately.)

Any thoughts?
Thanks,
Liz

    Debbie Moon · July 9, 2018 at 3:04 pm

    Hi Liz,
    Thanks for letting me know that your 23andMe data doesn’t have the i numbers that are listed for ACADS deficiency. I need to go back and edit that article to show which variants are available on the 23andMe version 4 chip vs. the version 5 chip. I’m guessing that you have the newer, version 5 data (since August 2017) and that the data isn’t available now.
    Debbie

      Liz Pacosa · July 9, 2018 at 3:19 pm

      Yes Debbie I did the test in 12/2017.
      Thank you.

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