Huntington’s is not genetic

Even doctors admit that it’s hard to distinguish between Huntington’s, Parkinson’s, and Alzheimer’s. Here’s an article saying that treatment for one of these diseases may work for the other two. 

Some researchers and physicians consider the differentiation between cortical and sub-cortical dementia important for patient diagnosis, but others remain skeptical that a significant difference exists. The major criticism of the studies that show variation between cortical and sub-cortical dementias is that there is pathological overlap between the sample groups that are used to model the two categories. These studies often assume that Alzheimer’s patients mostly have cortical dementia and HD or Parkinson’s patients preferentially exhibit subcortical dementia. Necropsies have shown, however, that the brains of both Alzheimer’s and HD patients exhibit a certain degree of both categories of dementia.

If in fact both cortical and subcortical dementia occur in Alzheimer’s, HD, and Parkinson’s patients, then these studies may be problematic. As a result, physicians are still trying to learn more about the differences between the pathologies of the diseases in hopes of finding a more reliable way of differentiating dementias. The ability to differentiate dementias may lead researchers and physicians to better diagnose and treat neurodegenerative diseases. [Source]

We’re going to go through the symptoms, but if you’ve been reading, you know how this goes.

So first, here are the symptoms:

Cognitive: amnesia, delusion, lack of concentration, memory loss, mental confusion, slowness in activity, or difficulty thinking and understanding

Muscular: abnormality walking, increased muscle activity, involuntary movements, problems with coordination, loss of muscle, or muscle spasms

Behavioral: compulsive behavior, fidgeting, irritability, or lack of restraint

Psychological: delirium, depression, hallucination, or paranoia

Mood: anxiety, apathy, or mood swings

Also common: tremor, weight loss, or impaired voice

Those look familiar. Are there any symptoms that aren’t covered between Alzheimer’s, Parkinson’s, and schizophrenia? 

“For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.” Wait…what? I thought the symptoms were the only things separating this from the other diseases?

And is it really genetic? It’s complicated, but the consensus is yes. Even though 10% of cases are “due to a new mutation.” But what about that field of epigenetics that basically says that your genes can change over time? Here’s the unabridged version.

HD is typically inherited from a person’s parents, although up to 10% of cases are due to a new mutation. The disease is caused by an autosomal dominant mutation in either of an individual’s two copies of a gene called Huntingtin. This means a child of an affected person typically has a 50% chance of inheriting the disease. The Huntingtin gene provides the genetic information for a protein that is also called “huntingtin”. Expansion of CAG (cytosine-adenine-guanine) triplet repeats in the gene coding for the Huntingtin protein results in an abnormal protein, which gradually damages cells in the brain, through mechanisms that are not fully understood. Diagnosis is by genetic testing, which can be carried out at any time, regardless of whether or not symptoms are present. This fact raises several ethical debates: the age at which an individual is considered mature enough to choose testing; whether parents have the right to have their children tested; and managing confidentiality and disclosure of test results.

This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene. In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder.

So if you have 27-39 repeats of this code you may or may not get the disease. But if you have 40 or more repeats, you almost always get the disorder. Wait…almost always? So you’re saying even the hard science isn’t foolproof.

The number of CAG repeats in an HD gene can be unstable when the gene is passed on to the next generation. That means the number of CAG repeats can increase or decrease when the gene is passed from parent to child. Wait, it varies from generation to generation? In the sole aspect that we’re using to call it genetic?

Older fathers are more likely to pass along the extended copy of this gene. We’ve talked about aging parents several times before. We know that the age of mothers closely correlates to Down Syndrome, while the age of fathers closely correlates to Dwarfism.

I have a question for you. How often do we test people with dementia for this CAG repeat? I’m guessing there is not much reason to test for Huntington’s when there is no family history. 

So in summary, here’s why I don’t think Huntington’s disease is genetic:

  • 10% of cases are “random” mutations
  • Even the hard science is not absolute
  • It gets more probable with aging dad’s
  • Epigenetics. Our genes change over time.

So if it is not genetic, then it is practically indistinguishable from Alzheimers and Parkinson’s.

Did science get it wrong? Maybe so. I think that a bunch of guys spent their lives studying batches of symptoms, it was the least we could do to name these batches of symptoms after them. All the other fields of science do it. Here’s the problem, the more classifications did not lead to more knowledge in this case. Because the symptoms are indistinguishable.

Sources:

  1. https://rarediseases.info.nih.gov/diseases/6677/huntington-disease
  2. https://en.hdbuzz.net/027
  3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3140172/
  4. https://www.alz.org/dementia/huntingtons-disease-symptoms.asp
  5. http://hdsa.org/what-is-hd/
  6. https://www.mayoclinic.org/diseases-conditions/huntingtons-disease/diagnosis-treatment/drc-20356122