From the Guidelines
In a family where one sibling has sickle cell disease (SCD) confirmed by high-performance liquid chromatography (HPLC) and another sibling has hemoglobin C (HbC), both parents are likely carriers of abnormal hemoglobin genes, and genetic counseling is advisable for future pregnancies. Each parent probably carries one normal hemoglobin A gene and one abnormal gene (either hemoglobin S or hemoglobin C) 1. The sibling with SCD inherited the hemoglobin S gene from both parents, resulting in hemoglobin SS disease. The sibling with HbC inherited the hemoglobin C gene from one parent and likely a normal hemoglobin A gene from the other parent, making them a carrier of hemoglobin C trait (AC). This family pattern suggests autosomal recessive inheritance of hemoglobinopathies.
Key Points to Consider
- For future pregnancies, there's a 25% chance of having a child with SCD, 25% chance of hemoglobin C disease, 25% chance of hemoglobin SC disease (a form of sickle cell disease), and 25% chance of normal hemoglobin in each pregnancy 1.
- Hemoglobin electrophoresis or HPLC testing of both parents would confirm their carrier status and help predict inheritance patterns more accurately 1.
- The management of SCD includes hydroxyurea, which has been shown to reduce the frequency of painful crises and may reduce the risk of stroke in children with SCD 1.
- Hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for SCD, and the decision to undergo HSCT should be made on a case-by-case basis, considering the individual's disease severity, age, and other factors 1.
Recommendations
- Genetic counseling is recommended for families with a history of SCD or other hemoglobinopathies to inform them about the risks and options for future pregnancies 1.
- Hemoglobin electrophoresis or HPLC testing should be performed on both parents to confirm their carrier status and predict inheritance patterns 1.
- Children with SCD should be screened for stroke risk using transcranial Doppler ultrasonography, and those with high risk should be considered for hydroxyurea therapy or other interventions to reduce stroke risk 1.
From the Research
Sibling with SCD on HPLC and HbC in other sibling
- Sickle Cell Disease (SCD) is an inherited disorder of hemoglobin, characterized by the formation of long chains of hemoglobin when deoxygenated within capillary beds, resulting in sickle-shaped red blood cells, progressive multiorgan damage, and increased mortality 2.
- The disease is diagnosed through newborn screening programs, where available, or when patients present with unexplained severe atraumatic pain or normocytic anemia 2.
- SCD is characterized by repeated episodes of severe acute pain and acute chest syndrome, and by other complications including stroke, chronic pain, nephropathy, retinopathy, avascular necrosis, priapism, and leg ulcers 2.
- Hemoglobin C (HbC) is a different type of hemoglobinopathy, and individuals with HbC may have a milder clinical course compared to those with SCD 3.
- The presence of SCD in one sibling and HbC in another sibling suggests that the siblings may have inherited different hemoglobinopathy genes from their parents 4.
- Hydroxyurea is a medication that can help reduce the frequency and severity of pain crises in individuals with SCD, and it may also be effective in preventing life-threatening neurological events in those with SCD at risk of primary stroke 5.
- Early diagnosis and treatment of SCD are crucial to improve survival and reduce the risk of complications, and universal newborn screening programs have been implemented in some countries to detect SCD and other hemoglobinopathies early in life 6.