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HEMOGLOBINOPATHIES

The hemoglobinopathies are a group of inherited disorders where there is abnormal production or structure of the hemoglobin molecule.Beta Thalassemia Trait

One beta globin variant present (beta plus OR beta null)

Mild anemia, low MCV on CBC

Mildly elevated HbA2 on Hb Elect

Beta Thalassemia Intermedia

Usually results from the presence of two beta plus variants

Lesser clinical severity than thalassemia major

Presentation includes moderate anemia, splenomegaly, moderate to severe hepatomegaly and bony changes

Transfusions not usually required to survive, but rather to improve quality of life;

Chelation therapy may be required

Beta Thalassemia Major

Two beta globin variants present (either one beta plus and one beta null or two beta null variants)

Severe anemia (fatal if untreated),

Secondary iron overload causing organ damage if untreated

Splenomegaly, growth delay

Management includes chronic transfusions, chelation therapy and ongoing monitoring for complications

SICKLE CELL DISEASE

There are two copies of the beta globin gene present in an unaffected individual, one on each chromosome 11.Normal CBC & Hb Elect

Alpha Thalassemia Trait

Two alpha globin gene deleted (CIS form = both genes deleted on the same chromosome; TRANS form one gene deleted from each chromosome)

Normal CBC & Hb Elect

Hemoglobin H Disease

Three alpha globin gene deleted

Hb H present on Hb elect

Variable clinical presentation

Hemoglobin H-Constant Spring

Two alpha globin gene deleted in CIS, plus a Constant Spring variant on a third alpha globin gene

Hb H present on Hb elect

More severe clinical course than Hemoglobin H disease

Likely to require transfusions

Moderate to severe splenomegaly, growth delay

Alpha Thalassemia Major

All four alpha globin gene deleted

Hb Barts present on Hb elect

Survival is possible through intrauterine intervention.There are two main types of hemoglobinopathies:

Thalassemia Syndromes

Disorders of decreased globin chain production

Alpha Thalassemia

Beta Thalassemia

Hemoglobin Variants

Disorders that produce structurally abnormal globin proteins

Hemoglobin S, C, E, etc.Alpha Thalassemia

There are four copies of the alpha globin gene present in an unaffected individual, two on each chromosome 16 Clinical findings depend on the number of alpha globin genes deleted

Silent Carrier

One alpha globin gene deleted.Beta Thalassemia

There are two copies of the beta globin gene present in an unaffected individual, one on each chromosome 11.Following birth, regular transfusion therapy and

chelation required.

HEMOGLOBINOPATHIES

The hemoglobinopathies are a group of inherited disorders where there is abnormal production or structure of the hemoglobin molecule. Hemoglobinopathies represent the most common single cell recessive disorders worldwide.

There are two main types of hemoglobinopathies:

Thalassemia Syndromes

Disorders of decreased globin chain production

Alpha Thalassemia

Beta Thalassemia

Hemoglobin Variants

Disorders that produce structurally abnormal globin proteins

Hemoglobin S, C, E, etc.

A combination of the two is also possible.

Alpha Thalassemia

There are four copies of the alpha globin gene present in an unaffected individual, two on each chromosome 16 Clinical findings depend on the number of alpha globin genes deleted

Silent Carrier

One alpha globin gene deleted.

Normal CBC & Hb Elect

Alpha Thalassemia Trait

Two alpha globin gene deleted (CIS form = both genes deleted on the same chromosome; TRANS form one gene deleted from each chromosome)

Normal CBC & Hb Elect

Hemoglobin H Disease

Three alpha globin gene deleted

Hb H present on Hb elect

Variable clinical presentation

Hemoglobin H-Constant Spring

Two alpha globin gene deleted in CIS, plus a Constant Spring variant on a third alpha globin gene

Hb H present on Hb elect

More severe clinical course than Hemoglobin H disease

Likely to require transfusions

Moderate to severe splenomegaly, growth delay

Alpha Thalassemia Major

All four alpha globin gene deleted

Hb Barts present on Hb elect

Survival is possible through intrauterine intervention.

Following birth, regular transfusion therapy and

chelation required.

Beta Thalassemia

There are two copies of the beta globin gene present in an unaffected individual, one on each chromosome 11. Beta plus variants cause decreased beta globin production, and beta null variants cause a complete absese of beta globin production. Clinical findings depend the type of beta globin variant(s) present.

Beta Thalassemia Trait

One beta globin variant present (beta plus OR beta null)

Mild anemia, low MCV on CBC

Mildly elevated HbA2 on Hb Elect

Beta Thalassemia Intermedia

Usually results from the presence of two beta plus variants

Lesser clinical severity than thalassemia major

Presentation includes moderate anemia, splenomegaly, moderate to severe hepatomegaly and bony changes

Transfusions not usually required to survive, but rather to improve quality of life;

Chelation therapy may be required

Beta Thalassemia Major

Two beta globin variants present (either one beta plus and one beta null or two beta null variants)

Severe anemia (fatal if untreated),

Secondary iron overload causing organ damage if untreated

Splenomegaly, growth delay

Management includes chronic transfusions, chelation therapy and ongoing monitoring for complications

SICKLE CELL DISEASE

There are two copies of the beta globin gene present in an unaffected individual, one on each chromosome 11. Hemoglobin S results from a specific variant in the beta globin genes, causing red blood cells form a "sickle" shape when deoxygenated, resulting in clinical consequences.

The type of features will depend on when a person has one or two copies of hemoglobin S variant present, or if other beta globin variants are also present.

Sickle Cell Trait

One hemoglobin S variant present

Hemoglobin S seen on Hb Elect

Minimal clinical issues with normal overall life expectancy

Hemoglobin C Trait

One hemoglobin C variant present

Slightly lower MCV

Hemoglobin C seen on Hb Elect

Clinically asymptomatic

Hemoglobin E Trait

One hemoglobin E variant present

Low MCV with microcytosis

Hemoglobin C seen on Hb Elect

Clinically asymptomatic

Sickle Cell Disease

Two hemoglobin S variants present

Onset in early childhood

.

Moderate to severe hemolytic anemia

Recurrent pain episodes **

Increased incidence and severity of certain infections

. Tissue infarction leading to organ damage and failure

Management includes:

Accurate, early diagnosis

Education/prompt recognition of complications

Prevention/treatment of infections

Management / aggressive treatment of acute vaso-occlusive events, chronic pain and hemolytic anemia

Screening for early signs of organ damage

Therapeutic intervention

Hemoglobin E Sickle Cell

One hemoglobin E variant AND one hemoglobin S variant present

Mild to moderate hemolytic anemia

Clinical expression is variable: some patients have no symptoms, whereas others have sickle cell-related complications.

Less severe as compared to more common forms of sickle cell disease.

Hemoglobin SC Disease

. Two beta globin gene variants present - hemoglobin S and hemoglobin C

Usually milder than sickle cell disease

Mild hemolytic anemia

Occasional infarctive crises

Splenomegaly

Increased viscosity of the blood

Hemoglobin S-Beta Thalassemia

One hemoglobin S variant AND one beta thalassemia variant present

Moderate to severe hemolytic anemia

Recurrent pain episodes

Splenomegaly

Clinical severity depends on the type of beta thalassemia variant inherited

Hemoglobin S-beta plus thalassemia tends to be less severe than Hemoglobin S-beta null thalassemia

Often difficult to distinguish between sickle cell disease and Hemoglobin S-beta null thalassemia on Hb elect