One single gene changes so much

Picture every cell in the body as a kitchen with a thick cookbook inside: around 20,000 recipes, the genes. Each recipe describes how the cell builds a particular tool, a protein.

Every recipe exists twice: one from mum, one from dad. In Finn, one of his two SLC6A1 recipes is changed – much like a swapped letter that makes the instructions useless. Usually it happens entirely by chance, as a new change (de novo); nobody did anything wrong.

Nerve cells constantly send each other messages. Some messengers act like an accelerator (“keep going!”), others like a brake (“calm down now”). The most important braking messenger is called GABA. It is a neurotransmitter – a chemical messenger nerve cells use to signal to each other.

A healthy brain keeps both finely balanced, thousands of times per second. That is what lets it learn, speak, move and settle down.

A brake must also be released again. After every signal a tiny “vacuum cleaner” in the cell wall pulls the GABA back in: the transporter GAT-1. The SLC6A1 recipe is exactly the blueprint for this cleaner.

Finn has too few cleaners. GABA lingers too long, the brake becomes unreliable – sometimes too strong, sometimes at the wrong moment.

Why are cleaners missing? The cell builds GAT-1 in a kind of factory and then ships it to the cell wall. Because of the change in the recipe, the part is folded wrongly. The cell's quality control notices, holds it back and scraps it.

Only the cleaners from the healthy copy remain – about half, or less. That isn't enough. This is exactly where therapies come in: a folding helper so more parts get through, or a gene therapy that supplies a new, healthy recipe.

Sounds paradoxical: why are there epileptic seizures if there is too much brake? The brain has pacemakers that keep the cortex in rhythm. If too much GABA constantly lingers there, these circuits start to oscillate – and suddenly large parts of the brain “march” in lockstep, about three times per second.

That is an absence seizure: a few seconds in which Finn isn't there. From outside you often only see a blank stare. On an EEG you see the typical spike-wave pattern.