What are haemoglobinopathies?

The haemoglobinopathies are any of a group of diseases characterised by abnormalities, both quantitative and qualitative, in the synthesis of haemoglobin (Hb). Most of them are genetically inherited but occasionally they can be caused by a spontaneous mutation. They are the world's most common mono-genic, autosomal, and recessive disease in humans.

For a haemoglobinopathy disease condition to exist, an abnormal haemoglobin or thalassaemia must be inherited from both parents resulting in a homozygous or double (compound) heterozygous condition.

A trait condition (carrier state) exists when a person inherits one normal Hb gene and one abnormal Hb gene. This person is healthy under normal circumstances and often is not aware they are carrying abnormal haemoglobin (there are some rare exceptions and extenuating circumstances where trait carriers can have symptoms).

Subdivisions of haemoglobinopathies

• Structural haemoglobin variants:
  • Quantitative defects caused by a reduced/imbalanced synthesis of a normal globin chain are referred to as the “Thalassaemias”.
  • Qualitative defects caused by the normal synthesis of an abnormal globin chain, often due to single amino acid substitutions in either the alpha or beta globin chains. A common example is the Glu to Val mutation at position six of the beta globin chain in sickle cell disease.
• Hereditary persistence of foetal haemoglobin:
  • genetic defects in the switch from foetal to adult haemoglobin synthesis .
  • foetal haemoglobin persists into adult life.

Thalassaemias

The term thalassaemia is used to describe globin gene disorders that result from a diminished rate of synthesis of one or more globin chains and consequently a reduced rate of synthesis of the haemoglobin or haemoglobins of which that chain constitutes a part; α thalassaemia indicates a reduced rate of synthesis of the α globin chain; similarly, β, δ, δβ and εγδβ thalassaemias indicate a reduced rate of synthesis of the b, δ, δ+β and ε+γ+δ+β chains, respectively. Thalassaemia is the most common single gene disorder known.

β-Thalassaemia

The β-thalassaemias are a group of conditions resulting from a reduced rate of synthesis of the β globin chain. More than 200 β gene mutations have been identified, occurring in a wide range of ethnic groups, and within each geographic population there are unique mutations.

β thalassaemia mutations are divided into two broad categories, β0  (β-zero) thalassaemia and β+ (β-plus) thalassaemia. In β0 thalassaemia there is either an abnormal gene that is not expressed or, less often, gene deletion. In β+ thalassaemia there is reduced, but not absent, expression of the abnormal gene so that even in the homozygous state there is still some haemoglobin A production.

β thalassaemia can be divided into three general categories:

• β thalassaemia trait: This state is characterised by heterozygosity of one deleted or mutated gene and one normal functioning gene, and may therefore also be referred to as β thalassaemia minor. Individuals with this trait are usually completely asymptomatic. 
• β thalassaemia intermedia: This state refers to a clinical phenotype with diverse genetic explanations. These individuals will have a homozygous or heterozygous β globin mutation that causes a decrease in β chain production, but not to the degree that chronic transfusion therapy is necessary. In comparison with a typical patient with β thalassaemia trait, there are significant clinical problems.
• β thalassaemia major or Cooley’s anaemia: β thalassaemia major refers to patients with homozygosity or compound heterozygosity for β thalassaemia who are dependent on blood transfusions to maintain life beyond early childhood.

 Tosoh offer our advanced G7 and G8  HPLC platforms to cater for your Haemoglobinopathy testing needs.  Please visit this page for more information.

Diagnosing thalassaemia traits and diseases

Thalassaemia may be suspected if an individual shows signs that are suggestive of the disease. However, in all cases, laboratory diagnosis is essential to confirm the exact diagnosis and to allow for the provision of exact genetic counselling about recurrence risks and testing options for parents and affected individuals.

Likewise, screening is recommended to determine trait status for individuals of high risk ethnic groups.

The following tests are used to screen and diagnose thalassaemia disease and/or trait:

• Full Blood Count (FBC)
• Free erythrocyte-protoporphyrin (or ferritin or other studies of serum iron levels)
• High Performance Liquid Chromatography (HPLC) for quantification of haemoglobin A2 and F
   

References:

Adrain Stephens; Haemoglobinopathies; The Biomedical Scientist; 2004, July, 1-4

Anita J. Catlin; Thalassemia: The facts and the controversies; Pediatric Nursing, November-December 2003, 29 (6), 447-451

Barbara J. Bain; Haemoglobinopathy Diagnosis; 2001 Blackwell Science Ltd

Nancy F. Olivieri; The β-thalassemias; The New England Journal of Medicine, 1999, July 8, 341 (2), 99-109

For further information visit also:

www.hbpinfo.com/en/
www.thalassemia.org/