Hemoglobinopathies in children nelson.pptx

pediatrics

1. Hemoglobinopathies

2. Hemoglobin is a tetramer consisting of two pairs of globin chains. Abnormalities in these proteins are referred to as hemoglobinopathies . Two hemoglobin gene clusters are involved in Hb production are located at the end of the short arms of chromosomes 16 and 11. The final hemoglobin distribution pattern that occures in childhood is not achieved until atleast 6 months of age.

3. Normal Hemoglobin structure Hemoglobin A is a tetramer composed of 4 subunits. 2 alpha and 2 beta Each subunit has a porphyrin ring which holds an iron molecule. This is the binding site of oxygen in the tetramer.

4. Types of hemoglobin HbA - α 2 β 2- Major hemoglobin in adult life HbA2- α 2 δ 2- Minor hemoglobin in adult life HbF - α 2 γ 2- Major hemoglobin in fetal life Other significant hemoglobin during early intrauterine life- Gower 1 , Gower 2 and Portland The normal hemoglobin pattern is >95% HbA , <3.5% Hb A2 and <2.5% HbF .

5. SICKLE CELL DISEASE Hemoglobin S ( HbS ) is the result of a single base pair change, thymine for adenine at the 6 th codon of the Beta-globin gene. This change encodes valine instead of glutamine in the sixth residue in the beta-globin molecule. In sickle cell anemia, HbS is typically as high as 90% of the total hemoglobin, whereas in sickle cell disease, HbS is >50% of all hemoglobin . T he most commonly used procedures for newborn diagnosis include thin- layer/isoelectric focusing (IEF) and high- performance liquid chromatography (HPLC).