Over the last few months while working on the AHC Documentary the crew has had to explore in details the ATP1A3 mutation and the sodium/potassium pump and lately we have been thinking about the possibility that AHC could be caused by GABA deficiency. That is, that the gene mutation somehow causes GABA deficiency which then causes the pump to malfunction
From what I have heard both from neurologists and parents of AHC champions this possibility has not been explored
When Sunna has episodes usually she gets both hemiplegia and dystonia and the same time. When we give her Midazolam both symptoms usually disappear for an hour max 2 two hours. The reason for the hemiplegia to stop might be because Midazolam enhances GABA so that the Sodium/potassium pump starts to work again until the Midazolam wears off.
The gene mutation results in malfunction of the pump, that somehow causes GABA deficiency
This pump uses up to 50% of the brain´s energy and therefore has a major impact on the brain´s function when it does not work properly.
The pump is interacting with the GABA pathway. GABA is an inhibitory neurotransmitter that has a calming effect on the brain and body.
If AHC patients have GABA deficiency that could explain many of the symptoms that they experience.
The symptoms include:
• Uncontrollably shakiness, trembling/twitching
• Overabundance of energy
• Blurry vision
• Cold/Unusually sweaty hands
• Muscle pains
• Memory loss
• Difficulty focusing or thinking
• Abnormally high craving for carbohydrates
• Trouble falling asleep
Listed above are purely physical symptoms. Some emotional or mental symptoms of GABA deficiency are as follows:
• Mood swings
• Feelings of despair
• Sudden influx of phobias where previously there was none
GABA can be bought from a pharmacy in the US as a dietary supplement.
While GABA may not ordinarily cross the blood–brain barrier, it is important to note that studies have shown that, within individuals for whom the blood–brain barrier has been damaged (temporarily for experimental purposes, or as a result of other problems), GABA does indeed have a positive effect, albeit with side effects. The only way to deliver GABA effectively is to circumvent the blood–brain barrier. Indeed, there are a small, limited number of over-the-counter supplements that are derivatives of GABA, such as phenibut and picamilon. Picamilon combines niacin and GABA and crosses the blood–brain barrier as a prodrug that later hydrolyzes into GABA and niacin.
GABA derived from drugs:
Baclofen produces its effects by activating the GABAb receptor, similar to the drug phenibut which also activates this receptor and shares some of its effects. However, baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential. The modulation of the GABAb receptor is what produces baclofen’s range of therapeutic properties.
Spasticity and involuntary movement syndromes, e.g., Parkinson’s, Friedreich’s ataxia, tardive dyskinesia, and Huntington’s chorea are all marked by low GABA when amino acid levels are studied. Trials of 2 to 3 g of GABA given orally have been effective in various epilepsy and spasticity syndromes.
I have spoken to scientist about this possibility of GABA deficiency and they tell me that GABA is high on their list as a possible cause for many AHC symptoms.
If this is the case then treatment for at least many of the AHC symptoms is possible today.
Keep in mind that this is just an idea from a parent of an AHC champion, always consult with your neurologist before trying a new drug or supplement.
Sigurdur Holmar Johannesson
President AHC Association of Iceland
Links on GABA and sodium/potassium pump
Gaba enhancer supplements (may not work because of the blood/brain barrier)