HBB, HBA1 and HBA2 genes


– C cell disease – OMIM#603903 https://omim.org/entry/603903

– Beta-Thalassemia – OMIM#613985 https://omim.org/entry/613985

1. The disease

The term sickle cell disease (SCD) encompasses an inherited group of blood disorders characterized by a structurally abnormal beta-globin subunit of hemoglobin, resulting from mutations in the HBB gene.  SCD is inherited in an autosomal recessive pattern – a mutation must be present in the copies inherited from both the mother and the father for the disease to manifest itself. The most common and serious type of SCD is SS sickle cell disease, which occurs when one pathogenic variant responsible for HbS is inherited from each parent. Other sickling disorders occur when the child inherits one pathogenic variant responsible for HbS from one parent and one pathogenic variant responsible for another abnormal form of haemoglobin (C, E or beta thalassemia) from the other parent. SCD is characterized by intermittent vaso-occlusive events and chronic haemolytic anaemia.

2. The symptoms

In sickle cell disease, babies are initially asymptomatic at birth and during the first 3-6 months of life, as the transition from primary foetal haemoglobin (HbF) production to adult hemoglobin (HbA) avoids the symptoms of the disease.  Lack of early signs or symptoms does not exclude the diagnosis.  

  • Initial presenting symptoms in babies with SCD include failure to thrive, repeated infection, painful dactylitis (pain and/or swelling of hands or feet) and pallor.
  • Complications may include, but are not limited to, the following:
    • Sepsis – the first sign of infection may be a high fever. These children require immediate medical attention. Children with SCD are very susceptible to pneumococcal infections.
    • Acute chest syndrome – a serious condition caused by infection and/or trapped sickled red blood cells in the lungs. Symptoms may include difficulty to breath, coughing and chest pain.
    • Hand-and-foot syndrome – this painful swelling of the hands and feet is due to severe vascular occlusion.
    • Splenic sequestration crisis – early signs include pallor, enlarged spleen and pain in the abdomen due to accumulation of sickled cells within the spleen. This complication can result in circulatory collapse and shock, with sudden death, if not recognized and treated immediately.
    • Aplastic crisis – the bone marrow temporarily stops producing red blood cells resulting in severe anaemia. The child may appear pale, tired, and less active than usual.
    • Stroke – cerebral vascular occlusion due to sickled cells can affect even very young children. Any loss of consciousness or weakness in an extremity should be evaluated promptly.

3. Actions to take in case of early diagnosis

  • This is not an emergency and further workup can be done in an ambulatory setting.
  • For SS sickle disease, additional laboratory findings may include: haemoglobin isoelectric focusing and/or high-performance liquid chromatography (HPLC) of an eluate of dried blood spots (biochemical newborn screening for Hbpathies); haemoglobin level (5-9 g/dL), decreased haematocrit, elevated total leukocyte count, with predominance of neutrophils, increased platelet count, low erythrocyte sedimentation rate, and peripheral blood smear demonstrating target cells, elongated cells, and characteristic sickle erythrocytes.
  • Sickle cell disease is a lifelong disease requiring lifetime management and regular follow-up with a Haematology Center.
  • Management for newborns affected with sickling diseases typically involves prophylactic penicillin injection every 21 days and vaccination against Pneumococcus, Meningococcus, and H. influenzae.  Strict compliance is crucial and provides an effective measure to reduce morbidity and mortality from pneumococcal infections in infants with all forms of sickle cell diseases.  An alternative antibiotic is available for children who are allergic to penicillin therapy.
  • Prescription pain medication and IV fluids may be indicated during sickling crises.
  • Bone marrow transplantation can be a curative treatment.
  • Research therapies, such as prevention of Hb S polymerization and the induction of fetal haemoglobin, show increasing promise in modulating the severity of sickle cell via a wide variety of pathways. Multiple gene therapy strategies are under study.
  • All siblings of babies diagnosed with a sickle cell disease should be tested; genetic counselling services should be offered to parents.

4. For more information:

For specific information about Beta-thalassemia, see: