THALASSEMIA

• autosomal recessive blood disease.• the genetic defect results in reduced rate of

synthesis of one of the globin chains that make up hemoglobin.

• Reduced synthesis of one of the globin chains can cause the formation of abnormal hemoglobin molecules, thus causing anemia,

Overview

Hemoglobin– oxygen-carrying component of the red blood cells– consists of two different proteins• alpha • beta.

If the body doesn't produce enough of either alpha or beta

proteins

the red blood cells do not form

properly and cannot carry sufficient

oxygen.

ANEMIA

Alpha Thalassemia

• Four genes (two from each parent) are needed to make enough alpha globin protein chains.

• commonly found in Africa, the Middle East, India, Southeast Asia, southern China, and occasionally the Mediterranean region.

• types– Silent Carrier State. – Alpha Thalassemia Trait or Mild Alpha Thalassemia. – Hemoglobin H Disease. – Hemoglobin H-Constant Spring. – Hydrops Fetalis or Alpha Thalassemia Major

Cooley's Anemia Foundation, Inc.

PATHOGENESIS OF Alpha THALASSEMIA

• relatively fewer α-globin • an excess of β- and γ-globin chains.• These excess chains form

– Bart's hemoglobin (γ4) in fetal life

– Hb H (β4) after birth.

• Prenatally, a fetus with α-thalassemia may become symptomatic because Hb F requires sufficient α-globin gene production,

• whereas postnatally, infants with β-thalassemia become symptomatic because Hb A requires adequate production of β-globin genes.

Inheritance Pattern for Alpha Thalassemia

Beta Thalassemias

• People whose hemoglobin does not produce enough beta protein

• It is found in people of Mediterranean descent, such as Italians and Greeks, Arabian Peninsula, Iran, Africa, Southeast Asia and southern China.

Pathogenesis of Beta Thalassemia

• Inadequate β-globin gene production– leading to decreased levels of normal hemoglobin

(Hb A)• imbalance in α- and β-globin chain production.

excess of α-globin chains relative to β- and γ-globin

chains;

α-globin tetramers (α4) are formed,

these inclusions interact with the red cell

membrane and shorten red cell survival,

leading to anemia and increased erythroid

production.

Types of Beta Thalassemia

• the lack of beta protein is not great enough to cause problems in the normal functioning of the hemoglobin.

• A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anemia.

Thalassemia Minor or Thalassemia Trait.

• lack of beta protein in the hemoglobin is great• bone deformities• enlargement of the spleen• patients with thalassemia intermedia need blood transfusions to improve their quality

of life, but not in order to survive.

Thalassemia Intermedia.

• This is the most severe form of beta thalassemia• complete lack of beta protein in the hemoglobin causes a life-threatening anemia• requires regular blood transfusions and extensive ongoing medical care. • lead to iron-overload which must be treated with chelation therapy

Thalassemia Major or Cooley's Anemia.

Inheritance Pattern for Beta Thalassemia

CLINICAL MANIFESTATIONS

• If not treated, children usually become symptomatic as a result of progressive hemolytic anemia,

• with profound weakness and cardiac decompensation during the 2nd 6 mo of life.

• Most infants and children have cardiac decompensation when the hemoglobin is 4.0 g/dL or less.

SummaryNumber of

affected genesHemoglobin

(g/dL)MCV (fL) Transfusion

dependentAlpha Thalassemia

Alpha-thal-2 trait 1 NORMAL None No

Alpha-thal-1-trait 2 >10 <80 No

Hemoglobin H 3 7-10 <70 +/-

Hydrops Fetalis 4 Incompatible with Life

Beta-Thalassemia

Beta-Thal Minor (trait)

1 >10 <80 No

Beta-Thal intermedia

2 7-10 65-75 +/-

Beta-Thal Majot 2 <7 <70 yes