What is the main cause of sickle cell disease?

The primary cause of sickle cell disease is a mutation in the beta-globin gene, leading to the production of abnormal hemoglobin known as hemoglobin S (HbS). This genetic alteration typically arises from a single nucleotide substitution in the DNA. When a person inherits this mutated gene, their red blood cells can form crescent or sickle shapes under low-oxygen conditions. Such shapes significantly affect the cells' ability to travel through blood vessels comfortably, resulting in blockages that can cause pain, organ damage, and a range of serious health complications associated with sickle cell disease.

Other options, such as a deficiency in vitamin B12 or iron, might lead to different types of anemia but do not cause the distinct and specific clinical features associated with sickle cell disease. Environmental toxins may have various health impacts, but they do not directly result in the genetic mutation responsible for the disease. Thus, the mutation in the beta-globin gene is the fundamental and direct cause of sickle cell disease, confirming why this option is the most accurate.