What is the risk of sickle cell disease in offspring when a individual with beta thalassemia (β-thalassemia) trait conceives with a sickle cell disease (SCD) carrier?

From the Guidelines

The risk of sickle cell disease in offspring when an individual with beta thalassemia (β-thalassemia) trait conceives with a sickle cell disease (SCD) carrier is 25% chance of having a child with SCD and a 50% chance of having a child who is a carrier.

Genetic Transmission

• SCD is an autosomal recessive genetic disorder, meaning that a child needs to inherit two abnormal genes (one from each parent) to have the disease 1.
• When a person with β-thalassemia trait (who is a carrier of one abnormal gene) conceives with a SCD carrier (who is also a carrier of one abnormal gene), there is a chance that their child will inherit two abnormal genes, one from each parent.

Risk of SCD in Offspring

• The risk of SCD in offspring is determined by the genotype of the parents, with a 25% chance of having a child with SCD, a 50% chance of having a child who is a carrier, and a 25% chance of having a child who is not affected and not a carrier 1.
• It is essential to document parental testing, including a CBC and hemoglobinopathy testing, to determine the genetic risk and provide accurate information about the clinical course of disease and trait, medical complications, and treatment of the specific SCD genotype relevant to the family 1.

From the Research

Risk of Sickle Cell Disease in Offspring

When an individual with beta thalassemia (β-thalassemia) trait conceives with a sickle cell disease (SCD) carrier, the risk of sickle cell disease in offspring can be understood through the following points:

• The offspring can inherit a combination of the β-thalassemia trait and the sickle cell trait, resulting in sickle/β-thalassemia, a condition with varying severity 2.
• The interaction between the β-thalassemia gene and the sickle gene can lead to a high level of hemoglobin A, which may have a favorable antisickling effect, but also decreased hemolysis, leading to increased blood viscosity and propensity for sickling 2.
• The inheritance of heterozygous alpha thalassemia 2 in conjunction with the mild β-thalassemia gene and sickle gene can further enhance the severity of the sickling disorder 2.
• Sickle cell disease can also result from rare variants, such as Sickle-(δβ)0-thalassemia, which can have a relatively stable clinical course but requires careful monitoring and follow-up 3.
• The genetic basis of β-thalassemia and sickle cell disease is complex, and genetic modifiers, such as α-globin genotype and innate ability to produce fetal hemoglobin (HbF), can influence the severity of the disease 4.

Possible Genotypes and Phenotypes

The possible genotypes and phenotypes of the offspring can include:

• Sickle/β-thalassemia (Sβ-thalassemia)
• Sickle cell disease (SCD)
• Sickle cell trait (SCT)
• β-thalassemia trait
• Other rare variants, such as Sickle-(δβ)0-thalassemia

Prevalence of β-Thalassemia Trait among SCD Patients

Studies have shown that the co-inheritance of β-thalassemia trait and SCD is not uncommon, with a prevalence of 10.6% in some populations 5. This highlights the importance of evaluating the chromatographic patterns and red blood cell indices of SCD patients to determine the co-inheritance of other hemoglobin variants and β-thalassemia trait.