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.