Which are the causes of Chorea-acanthocytosis ChAc?

Chorea-acanthocytosis (ChAc) is a rare genetic disorder characterized by abnormal movements (chorea) and the presence of misshapen red blood cells (acanthocytes). The exact cause of ChAc is a mutation in the VPS13A gene, which provides instructions for producing a protein called chorein. This mutation leads to a deficiency or dysfunction of chorein, resulting in the symptoms associated with ChAc.

Genetic Mutation: ChAc is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated VPS13A gene (one from each parent) to develop the disorder. If both parents carry one copy of the mutated gene, each child has a 25% chance of inheriting two copies and developing ChAc.

Role of Chorein: Chorein, the protein produced by the VPS13A gene, is primarily found in the brain and red blood cells. Its exact function is not fully understood, but it is believed to play a role in maintaining the structure and function of certain cells, particularly in the basal ganglia, a region of the brain involved in movement control.

Cellular Dysfunction: The deficiency or dysfunction of chorein in ChAc leads to cellular abnormalities, particularly in the basal ganglia. This disruption affects the communication between brain cells and impairs the regulation of movement, resulting in the characteristic choreic movements seen in ChAc.

Acanthocytosis: Another hallmark feature of ChAc is the presence of acanthocytes, which are abnormally shaped red blood cells. These cells have spiky projections on their surface and are thought to be a consequence of the underlying genetic mutation. The exact mechanism by which the VPS13A mutation leads to acanthocytosis is not fully understood, but it is believed to involve alterations in the lipid composition of the red blood cell membrane.

Other Factors: While the VPS13A gene mutation is the primary cause of ChAc, other factors may influence the severity and progression of the disorder. Genetic modifiers, environmental factors, and individual variations in other genes may contribute to the variability in symptoms observed among affected individuals.

In conclusion, Chorea-acanthocytosis is caused by a mutation in the VPS13A gene, leading to a deficiency or dysfunction of the chorein protein. This disruption affects the basal ganglia and impairs movement control, resulting in choreic movements. Additionally, the presence of acanthocytes in the blood is a characteristic feature of ChAc. While the genetic mutation is the primary cause, other factors may influence the manifestation of symptoms. Further research is needed to fully understand the underlying mechanisms of ChAc and develop potential treatments.