Hemoglobinopathies

Hemoglobin variants and thalassemias, a growing public health problem

PATHOLOGY

Hemoglobinopathies are the most common monogenic disease in Human. Around 7 % of the worldwide population are carriers and 2.7 ‰ births are affected by hemoglobinopathies. These hemoglobin disorders are traditionally endemic among populations originating from Southern Europe, Africa, Middle East and Asia. Due to population migrations, these hemoglobin disorders are occurring today widely across the world.

Hemoglobin variants and thalassemias are two genetically distinct hemoglobin abnormalities. Thalassemias are characterized by a reduced synthesis of the normal globin chain due to gene deletions or mutations. The most common thalassemias are alpha- and beta-thalassemias. The hemoglobin variants are caused by amino acid substitutions in either globin chain. More than 1600 hemoglobin variants have been characterized but only a few are common: Hb S, Hb C, Hb E and Hb D-Punjab.

Hemoglobinopathies can present several clinical symptoms, from benign (mild microcytosis) to the most severe (sickle cell disease, Hb Bart’s hydrops fetalis, …) with multiple organ damage, requiring lifelong transfusions. Diagnosis and follow-up of hemoglobinopathies depend on the presence of abnormal hemoglobin fractions on electrophoresis profiles and the quantification of Hb A2.

Births with a pathological hemoglobin disorder (per 1,000 live births). Source: WHO, 1996

TEST PRINCIPLE

Hemoglobin electrophoresis (agarose gel or capillary electrophoresis) is a well-established technique routinely used in clinical laboratories for screening samples for hemoglobin abnormalities. Normal hemoglobin fractions are separated in the following order: Hb A2, Hb F and Hb A. Hemoglobin is a complex molecule composed of two pairs of polypeptide chains.

The type of hemoglobin is determined by the presence of globin chains:

  • Hb A = α2β2
  • Hb F = α2γ2
  • Hb A2 = α2δ2

Hemoglobin variants  are characterized by the presence of abnormal hemoglobin fractions where substitution of amino acids caused by a mutation, leads to modified surface charge and consequently different electrophoretic mobilities. Thalassemias may present abnormal fractions (Hb H or Hb Bart’s) and/or abnormal values for normal hemoglobin (low or high level of Hb A2 for example).

 

Test Indications

The Sebia hemoglobin electrophoresis assays provide:

  • Qualitative separation of individual hemoglobin fractions allowing the identification of hemoglobin variants (in particular Hb S, Hb C, Hb D and Hb E)
  • Quantitative analysis of hemoglobin fractions with particular interest (such as Hb A2 for thalassemias diagnosis).

Part of the product portfolio, the Sebia capillary electrophoresis is a well-established breakthrough technology that performs all sequences automatically, from blood hemolysate preparation to precise sample separation. The final result is a clear-cut and precise profile, with quantification and presumptive identification of the hemoglobin fractions.

SEBIA assays available for this pathology

MINICAP HEMOGLOBIN(E)

CAPILLARYS HEMOGLOBIN(E) 

CAPILLARYS NEONAT Hb 

HYDRAGEL HEMOGLOBIN(E) K20 

HYDRAGEL ACID(E) HEMOGLOBIN(E) K20 

HYDRAGEL HEMOGLOBIN(E) 

HYDRAGEL ACID(E) HEMOGLOBIN(E)