What is Alternating Hemiplegia of Childhood?

Alternating Hemiplegia of Childhood (AHC) is a rare neurological disease which is caused (in about 80% for the cases) by a mutation of the gene ATP1A3. That causes malfunction of the sodium-potassium pump.

The sodium-potassium pump is a biological structure located on the surface of the cell membrane and the membranes of the mitochondria. Its function is to drive sodium and potassium ions in and out of the cell. The major part of it is a protein called Na+ /K+-ATPase, which functioning is affected by the mutation.

Symptoms

The patients with AHC exhibit a wide range of symptoms. These include tonic attacks (lack of muscle tone), dystonia (stiffening of the limbs), ataxia (lack of coordination when performing voluntary movements), nystagmus (rapid, uncontrollable, horizontal, vertical or rotary eye movements), other ocular motor abnormalities or delays in general development.

In the course of the illness, up to 50% of the patients may develop epilepsy.

Daily activities or environmental conditions may trigger an episode. These could be temperature extremes, odors, physical activities, direct sunlight, foods, medications, or emotional response like anxiety, stress, or fear.

Diagnostic criteria

• The onset of symptoms is before 18 months of age.
• Repeating episodes of hemiplegia which alternate in laterality (left to right and vice verse)
• Episodes of hemiplegia on both sides of the body of quadriplegia (paralysis of all four limbs)
• Relief from the symptoms during sleep which may resume after waking.
• Other disturbances like tonic or dystonic episodes, abnormal eye movements or other autonomic symptoms which may occur either in addition to the episodes of hemiplegia or independently.
• Evidence for development delay or neurological findings like dystonia (stiffening of the limbs), choreoathetosis (involuntary movements), or ataxia (lack of balance and coordination when performing voluntary movements).

The incidence rate of AHC is about 1 per 1,000,000. However, the actual frequency may be even higher because of misdiagnosing the disorder due to a lack of awareness of the disease and variability in its clinical characteristics.

DNA analysis is the most accurate way of diagnosing the disease.

Therapy

After the definition of AHC in 1971, there have been different theories and attempts for finding a drug relief for the disease. Several global research projects have been testing different drug compounds on mice models or stem cells, thus seeking to find a candidate drug for clinical trials and possible future treatment.

Currently, the possibilities for medical treatment are minimal — the only medication that has a positive effect on patients with AHC is Flunarizine. In up to two-thirds of the patients, Flunarizine is relatively effective in reducing the severity, intensity, and duration of the dystonic or hemiplegic episodes.

Gene therapy

Leading scientists from several universities around the world and different scientific institutes are participating in joint international research of gene therapy for AHC. It consists of inserting a functional copy of the ATP1A3 gene in a virus (adeno-associated virus or AAV), that is devoid of its harmful load ant its ability to reproduce. Then it needs to be injected in the spinal-cerebral fluid to transfer the functional gene into the brain cells. Thus, by providing an additional functional copy of the gene, it is expected that they can achieve permanent curing of the cell.

Disease development

Although the disease is called alternating hemiplegia in childhood, it is not present only during childhood. With the time and the growing of the child, the episodes and the symptoms may change, including an increase in frequency in some cases.

Every child with AHC is different and unique and it can be more or less affected by the disease. The older the child becomes, the more tangible the development issues may become after each episode. The development delay may occur in different ways — from motor difficulties, through speech and cognitive skills to communication problems. Scientists have proved that AHC can cause a permanent and progressive mental and neurological delay. Therefore, early diagnosis is essential to minimize these adverse consequences.

Public awareness of AHC may be the key to the early diagnosis of children suffering from this rare and severe disorder.