Which are the causes of Hereditary Spherocytosis?

Hereditary Spherocytosis (HS) is a genetic disorder characterized by the presence of spherical-shaped red blood cells (RBCs) instead of the normal biconcave disc-shaped RBCs. This condition is primarily caused by mutations in genes that encode proteins involved in maintaining the structural integrity of RBCs.

Ankyrin, spectrin, band 3, and protein 4.2 are the four main proteins affected in HS. Mutations in these genes lead to a weakened cytoskeleton network within the RBCs, resulting in their spherical shape and increased susceptibility to destruction by the spleen.

Ankyrin is responsible for attaching the cytoskeleton to the RBC membrane, while spectrin forms a lattice-like network providing structural support. Mutations in the ankyrin or spectrin genes disrupt this network, causing the RBCs to lose their flexibility and become more prone to damage.

Band 3 is an integral membrane protein that helps maintain the shape and stability of RBCs. Mutations in the band 3 gene can impair its function, leading to abnormal RBC morphology.

Protein 4.2 plays a role in stabilizing the lipid bilayer of RBCs. Mutations in the protein 4.2 gene can result in membrane instability and spherocytic RBCs.

Hereditary Spherocytosis is an autosomal dominant disorder, meaning that an affected individual has a 50% chance of passing the condition on to each of their children. However, in some cases, it can also be inherited in an autosomal recessive manner.

Family history is a significant risk factor for HS. If one or both parents have the condition, their children are at an increased risk of inheriting the mutated genes and developing HS.

While the exact cause of HS is genetic, certain environmental factors can exacerbate the symptoms. These include infections, certain medications, and exposure to extreme temperatures.

Diagnosis of HS involves a combination of clinical evaluation, blood tests, and genetic testing. Blood tests can reveal characteristic features of spherocytosis, such as increased mean corpuscular hemoglobin concentration (MCHC) and decreased mean corpuscular volume (MCV).

Treatment for HS focuses on managing symptoms and preventing complications. This may involve folic acid supplementation to support RBC production, blood transfusions in severe cases, and, in some instances, surgical removal of the spleen (splenectomy) to reduce RBC destruction.

In conclusion, Hereditary Spherocytosis is primarily caused by mutations in genes encoding proteins involved in maintaining the structural integrity of RBCs. These mutations lead to the characteristic spherical shape of RBCs and increased susceptibility to destruction. While genetic factors play a significant role, environmental factors and family history also contribute to the development of this condition.