Short-chain Acyl-CoA Dehydrogenase Deficiency – Inborn Errors of Metabolism

 

Fatty Acid Molecules    (Creative Commons Wikimedia)
Fatty Acid Molecules (Creative Commons Wikimedia)

SCAD Deficiency

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 (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, from which the Kreb’s cycle begins.  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 fatty acids for fuel.

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

Genetic polymorphisms

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

  • rs1800556 (T,  c.511C>T) –   The T allele is listed as pathogenic for SCADD [ref]
  • rs28940874 (T,  c.575C>T) -The T allele is listed as pathogenic for SCADD [ref]
  • rs61732144 (T, c.319C>T) -The T allele is listed as pathogenic for SCADD [ref]
  • rs28941773 (T, c.1058C>T) -The T allele is listed as pathogenic for SCADD [ref]
  • rs28940872 (T, c.1147C>T) -The T allele is listed as pathogenic for SCADD [ref]
  • i5007491 (A, rs121908005) -The A allele is listed as pathogenic for SCADD[ref]
  • i5007492 (T, rs121908006)-The T allele is listed as pathogenic for SCADD[ref]
  • i5007490 (A, c.625G>A, rs1799958) – This one is a fairly common polymorphism, but 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 knowing that most infants who carry the pathogenic alleles do not have 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]

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]

Another recommendation for SCADD in children is to make sure they eat regularly to prevent hypoglycemia.

Mouse studies show that a low-fat diet (or a ‘not high-fat diet’) may be helpful.  One study looked at the mitochondrial energy changes in mice bred to be ACADS deficient.  The study found that “these results point to an oxidative shortage in this genetic model and support the hypothesis of a lower hepatic energy state associated with SCAD deficiency and 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.

Diet and Supplements:

For those who are heterozygous for one of the pathogenic variants listed above, just 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.  I know for myself (heterozygous for one of the variants), I felt really terrible and fatigued when trying a ketogenic (low carb) diet.

Riboflavin supplements may be worth trying if you don’t think you get enough via your diet.  You can get powdered riboflavin from Bulk Supplements if you don’t want any added excipients or junk in your supplement.

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