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Hemoglobinopathies are a group of inherited disorders in which there is abnormal production or structure of the globin moiety of the hemoglobin molecule. Hemoglobinopathies, which include the thalassemias and structural hemoglobin (Hb) variants, are the most common group of autosomal recessively inherited monogenic disorders of Hb production and pose a significant health burden in India.(1,2)<\/p>\n
There are thousands of genetic abnormalities possible in the globin genes, many of which are asymptomatic. Proper and timely diagnosis is imperative to ensure optimal treatment and also to offer genetic counselling to those who may be carriers. Hemoglobinopathies can be broadly classified into:<\/p>\n
These are caused by a qualitative defect in the genetic code that leads to structural change in the hemoglobin molecule. Most alpha and beta globin chain variants are clinically silent and are discovered incidentally or during screening of family members of a patient.(3) A few variant hemoglobins are capable of causing severe disease, especially in homozygous state (e.g. HbS) or when inherited in conjunction with another variant or a thalassemia mutation. Common examples of variant hemoglobins in India include HbS, HbE and HbD. These hemoglobinopathies are prevalent in certain geographies and communities, e.g. HbE in the north eastern states of India.(4)<\/p>\n
These are quantitative defects of Hb resulting in reduced levels of a globin chain in red cells. As a result, one or the other globin chains will accumulate, form aggregates and then precipitate, leading to premature intramedullary or intravascular destruction of RBCs.<\/p>\n
Mutations in gamma and delta globin genes can also cause thalassemic disorders ranging from clinically silent (Hereditary persistence of fetal hemoglobin \u2013 HPFH) to symptomatic (delta-beta thalassemia). Rarely, thalassemic mutations can result in altered hemoglobin structure (eg: Hb Lepore). An example of delta globin chain mutation not uncommonly seen in India is HbA2 Saurashtra.(6)<\/p>\n
The laboratory diagnosis of hemoglobinopathies has evolved quite a bit over the years, progressing from gel electrophoresis all the way to next generation sequencing.<\/p>\n
\u201cIn most cases, a well elicited family history and parental testing in combination with HPLC is sufficient for definitive diagnosis of common Hb variants.\u201d<\/i>(4)<\/p>\n
There are 2 broad categories of tests for diagnosis\/screening of hemoglobinopathies:(4)<\/p>\n
These are the methods of choice in the present day, with more advanced DNA based tests being used only for cases which cannot be resolved using protein-based methods. The routinely used protein-based methods are as follows:(4)<\/p>\n
Table 1 \u2013 Comparison of Protein-Based Methods<\/i>(4)<\/p>\n chromatography (HPLC)<\/td>\n (IEF)<\/td>\n These are almost never used as first-line tests. They do have immense significance and potential in prenatal and newborn screening. The commonly used methods are:(4)<\/sup><\/p>\n Table 2 \u2013 Comparison of DNA-Based Methods(4)<\/p>\n\n\n
\n <\/td>\n Advantages(4)<\/td>\n Disadvantages(4)<\/td>\n<\/tr>\n \n High performance liquid<\/p>\n \n \n
\n \n
\n Isoelectric focusing<\/p>\n \n \n
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\n Capillary electrophoresis<\/td>\n \n \n
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\n Electrophoresis (cellulose acetate, citrate agar)<\/td>\n \n \n
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DNA-based methods<\/b><\/h3>\n
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