Inborn errors of metabolism: Energy from fats

The term "inborn error of metabolism" refers to a bunch of different genetic conditions that disrupt cellular metabolism. These conditions are caused by rare mutations and are usually identified in infancy or through newborn bloodspot screenings.

Fatty acid oxidation disorders are one type of inborn error of metabolism, which affects the use of fats for energy in the mitochondria

There are three primary genes to look at for fatty acid oxidation disorder on Genetic Lifehacks, and these genes encode the enzymes that metabolize short-chain, medium-chain, or long-chain fatty acids.

Why is this important since these disorders are rare?

Carrying one copy of a mutation for a fatty acid oxidation disorder isn't all that rare. Most people are completely unaware of the mutation, but there are specific circumstances when it can become noticeable.

Ketosis is when your body switches to primarily using fats for energy. This occurs when you avoid eating carbohydrates or when fasting. For someone with a single copy of a fatty acid oxidation disorder mutation, this may cause them to feel lethargic - or just bad - when on a keto diet. It may also cause someone to have low blood sugar problems after hard exercise while fasting.

The first article below on long-chain fatty acids is new this week, and the other two are newly updated. If you are considering going keto or doing intermittent fasting, it's worthwhile to take a minute to check your genes.

Gratefully yours,

Debbie

---

Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD)

Key takeaways:
~ VLCADD is a genetic disorder caused by mutations in the ACADVL gene that impair the use of long-chain fatty acids for energy.
~ Symptoms and severity vary according to the mutation and can include hypoglycemia, heart problems, and muscle pain.
~ VLCADD is inherited in an autosomal recessive pattern, meaning that an individual generally needs two copies of the mutation to have the disease.

Read the rest of the article here

---

Medium Chain Acyl-CoA Dehydrogenase Deficiency: Check your genetic data

Key takeaways:
~ Medium-chain acyl-CoA dehydrogenase enzyme deficiency makes it hard to use medium-chain fats for energy or to fast and go into ketosis.
~ MCAD deficiency is caused by two copies of mutations in the ACADM gene. It is usually discovered in infant blood screenings.
~ People with one copy of an ACADM mutation may have mild symptoms, including problems with a ketogenic diet.

Read the rest of the article here

---

Short-chain Acyl-CoA Dehydrogenase Deficiency

Key takeaways:
~ Short-chain Acyl-CoA Dehydrogenase Deficiency (SCADD) is a genetic disorder that affects the body’s ability to use short-chain fatty acids for energy.
~ Mutations in the ACADS gene cause this inborn error of metabolism.
~ SCADD is an autosomal recessive disorder, meaning that two copies of the mutation are needed.
~ Carriers of one copy of a mutation may have mild symptoms under stress and may struggle with a ketogenic diet or a prolonged fast.

Read the rest of the article here

---

New on Longevity Lifehacks:

Inflammation + Insomnia = Depression

In this Longevity Lifehacks article, I discuss a new study involving older adults that found that inflammation alone usually doesn't trigger depressive symptoms. However, inflammation combined with insomnia significantly increases the risk of depression. It's an interesting study that brings together two known causes of depression and expands on the mechanism.

What I've been reading:
1. Population-scale sequencing resolves correlates and determinants of latent Epstein-Barr Virus infection

Whole genome sequencing files contain more information than just nuclear DNA. They can also pick up viral and bacterial sequences, as well as possibly cancer mutations, as background noise.

In this new (preprint) study, researchers are looking at the non-human DNA from whole genome sequences - specifically Epstein-Barr virus DNA. Using whole genome sequencing data from over 500,000 people, along with serological information for a subset of the population, the researchers were able to come up with a method of determining EBV status based on the WGS data. Then, they combined that with the electronic health record data for the individuals to see if there was a connection. The researchers found that latent EBV DNA is a polygenic trait and that it is a marker for respiratory, cardiovascular, and autoimmune diseases. This is a fascinating study.

Related GL article: Epstein-Barr Virus connections and susceptibility

2. Utility of glucagon-like-peptide-1-receptor agonists in mast cell activation syndrome

Mast cells have GLP1 receptors, and this case series looked at the effect of GLP-1 receptor agonists on mast cell activation syndrome patients. Of the 47 MCAS patients, 89% had a clinically relevant improvement of MCAS-associated problems when using a GLP-1 RA.

Related GL article: Mast cell activation syndrome