SCD is a hereditary disease. The genetic material (the DNA) is contained in the chromosomes. Every child receives 46 chromosomes from its parents, 22 chromosomes and one sex-determination chromosome from the mother and 22 chromosomes and one sex-determination chromosome from the father. The chromosomes are the carriers of the genes. In SCD, a change (mutation) on the short arm of chromosome 11 in the beta globin gene leads to an alteration of the genetic material. As a result, a different genetic code is used to create and structure the body. In this specific case, it leads to the creation of an abnormal beta globin chain that causes a change in the composition of the HbA1.

SCD is autosomal recessive, meaning that you will have the disease if you receive the mutated gene from both parents. As a result, both boys and girls can have this disease, it is not a sex-linked disease. It is also possible to inherit the mutated gene from one parent and the normal unchanged gene from the other. You would then be a carrier of the disease. As a carrier of SCD, you have enough unchanged beta globin, meaning that your body is still able to properly create hemoglobin A1. Still, you may pass your genetic predisposition to your children.

The genes involved in HbA1 and HbF production are located closely together on chromosome 11. Hemoglobin is made by two genes from the alpha globin gene cluster on chromosome 16 and two genes from the beta globin gene cluster on chromosome 11. These four globin chains, i.e. two alpha globin chains and two beta globin chains, together form the HbA1 hemoglobin, which is the most important type of hemoglobin for humans from the age of four months onward.

Compound heterozygote sickle cell disease occur when there is a different mutation in each beta globin gene, as opposed to homozygote sickle cell disease, where you have the same S mutation (HbSS) in each beta globin gene.

Compound heterozygote sickle cell disease can occur in the following forms:

• Hemoglobin SC sickle cell disease: one parent passes the HbS gene, and the other the HbC gene; the child will then have HbSC sickle cell disease. This will produce symptoms that are similar to those of HbSS SCD. The symptoms are generally slightly milder. However, the treatment is the same. The symptoms that go with this condition are more severe than those of homozygote HbC (HbCC) disease.
• Sickle cell- beta thalassemia sickle cell disease: one parent passes the HbS gene and the other the beta thalassemia gene. This will give you a combination of sickle cell disease and beta thalassemia, which is known as HbS- beta thalassemia SCD. This comes with symptoms that are consistent with both diseases, although the severity of these symptoms can vary depending on how much normal hemoglobin the beta globin genes still produce.
  
  If there is hardly any normal hemoglobin production (HbS beta 0-thalassemia), this is a severe condition. But if the beta globin genes still produce a fair amount of normal hemoglobin (HbS beta +-thalassemia), the symptoms will be less severe and there will be fewer sickle cell crises. This type of SCD occurs mainly in people who originate from Mediterranean countries (Italy, Greece, Morocco, Turkey). In some cases, this type of SCD acts like a severe form of beta thalassemia (or beta thalassemia major) and requires treatment with blood transfusion.