خالد نافع

HEMOGLOBINOPATHIES Definition : Hemoglobinopathies are inherited disorders in which Mutation in or near the globin genes alter the structure of amino acid sequences(QUANTITATIVE) Hb-S  B6 glu val Hb-C  B6 glu lys or the rate of synthesis of a particular globin chain(QUALITATIVE).

Defective haemoglobin

Sickle cell anaemiaIt results from single base change in the DNA coding for the amino acid in the sixth position in the b-globin chain.This leads to an amino acid change from glutamic acid to valine HbS will be formed instead of the normal Hb.

INTRODUCTION

Sickle Cell Anemia is a hereditary disease which is cause by a disorder in the blood, a mutation in the Hemoglobin Beta Gene which can be found in the chromosome 11. This disease causes the body to make abnormally shapes red blood cells. A normal red blood cell is shaped as a round donut while the abnormal red blood cell has a “ C “ form.

Sickle cell anaemia: Introduction

Hb S is insoluble and forms crystals when exposed to low oxygen tension. Deoxygenated sickle Hb polymerizes into long fibrils. The red cells sickle may block the different areas of the microcirculation or large vessels causing infarcts of various organs. It is widespread in Africa.

ORIGIN

The origin sickle cell anemia is thought to be originated from Africa and India, and then started spreading as people move and mated.

INTRODUCTION CONT’

Hemoglobin Beta Gene (HBB) also known as Beta Globin is a protein that resides in the red blood cells. The HBB is 146 amino acids long and its molecular weight is 15,867 Daltons. The molecules of the hemoglobin are responsible to carry oxygen through the body. The HBB is found in part 15.5 of the chromosome 11.

RISK FACTORS

A risk factor is what increases the chance of getting a disease or condition. The risk of having sickle cell anemia is dying of strokes and heart attacks dramatically increase.

Pathophysiological effects of sickled cells

Sickle cell crisis

DIAGNOSIS

Howell Jolly Body
Erythroblast

Haemoglobin Electrophoresis (alkaline pH )

Hb C
Hb S
Moves in same position as Hb A2
HbA
Anode
Haemolysate applied
Cathode

δ δ α α α s s α α γ γ α Hb S

Hb A2
Hb F
Genotype αααα βsβs δδ γγ Haemoglobins Produced :
Diagnosis: Hb SS Disease
Laboratory diagnosis of sickle cell anaemia made by presence of only Hb S, Hb A2, and Hb F on Hb electrophoresis with no Hb A, a positive sickling test and presence of sickle cells in blood film


Haemoglobin Electrophoresis: Hb A 0 % Hb S 87.0 % Hb F 9.7 % Hb A2 3.3 %

TREATMENT

THALASSEMIA

Clinical manifestations of thalassemia

Pathogenesis cont.

δ δ α α α γ γ α

Hb A2
Hb F
Diagnosis: β Thalassemia major Genotype αααα - - δδ γγ Haemoglobins Produced
Laboratory diagnosis of β thalassemia major made by CBC, absence of Hb A, with increased Hb F. Some patients have small amounts of Hb A if some β globin chain is produced.


α-THALASSAEMIAS

α Thalassemia cont.

Normal Control
Abnormal Control
Abnormal Control
Patient Hb H
HbA
HbA2


Hb –H Diagnosis Haemoglobin Electrophoresis: Hb A 91.5 % Fast moving band 8.5% Hb A2 and Hb F decreased

Hb H Preparation

Hb H inclusions in RBCs

TREATMENT cont