ThalassemiaIntroduction:
Thalassemia is an inherited anemia. It is the most common among the hemoglobinopathies.
It is a microcytic, hemolytic anemia due to an unbalanced
hemoglobin synthesis with a defect in one of the polypeptide chains. Adult hemoglobin
(called hemoglobin A) consists of two polypeptide chains, called alpha and beta.
But normal blood also contains less than 2.5% of hemoglobin A2, which on electrophoresis
can be seen as a different, distinct line. This consists of two polypeptide chains,
called alpha and delta. To make this even more complicated, there is hemoglobin
F, which is the main hemoglobin during fetal growth, which has gamma polypeptide
chains instead of the beta polypeptide chains of adult hemoglobin. This is important
as in thalassemia hemoglobin F, which is normally present to less than 2% of the
total hemoglobin, will be present to as much as 90%. Depending on which defect
is present in the polypeptide chain synthesis of hemoglobin, the thalassemia is
called alpha-thalassemia (defective alpha chain synthesis), beta-thalassemia (defective
beta chain synthesis), etc. The most common form of thalassemia is beta-thalassemia.
Thalassemia is particularly common among Mediterranean people and in people of
African or Southeast Asian ancestry. Alpha-thalassemia has a more complicated
inheritance pattern as there are 4 genes involved that code for this hemoglobinopathy.
Defects in all 4 genes are incompatible with life and lead to a spontaneous abortion
during pregnancy. When 3 genes are affected, this is called hemoglobin H disease,
where alpha chain production is severely impaired. Symptoms:
With beta-thalassemia
major (the homozygous form) there will be a severe hemolytic anemia at a young
age (1 or 2 years) with jaundice and iron overload. Similar to sickle cell anemia
there leg ulcers and gall stones develop. There is also often a massive enlargement
of the spleen (splenomegaly), where the spleen suddenly destroys and increasing
amount of the circulating red blood cells. This is called acute splenic sequestration
crisis. Due to the ongoing removal of red blood cells through hemolysis, there
is a chronic stimulation of the bone marrow so that bone marrow develops in unusual
areas such as the skull bones and the long bones. Growth impairment and pathological
fractures are common and puberty can also be delayed. Heart failure at a young
age can occur from iron deposits released by the decaying red blood cells or from
repeated blood transfusions. Liver involvement is usual with tissue damage from
iron deposits (called hepatic siderosis) and the development of liver cirrhosis
with impaired liver metabolism. Patients with hemoglobin H disease have an enlarged
spleen and are symptomatic with their hemolytic anemia. The heterozygous forms
of the various subtypes of thalassemia (also termed “thalassemia minor”) are
often asymptomatic. Diagnostic tests for thalassemia: With a microcytic hemolytic
anemia in a person whose relatives have a history of thalassemia diagnostic tests
are needed to rule this condition in or out. The standard tests for a hemolytic
anemia are ordered, serum bilirubin, iron levels, ferritin, a blood smear and
quantitative hemoglobin studies including electrophoresis. Hemoglobin F is determined
as often this will be elevated indicating the presence of a hemoglobinopathy.
A referral to a hematologist should be done as the diagnostic tests may need to
be refined depending on what the exact results were. For instance, a bone marrow
biopsy of aspirate may be required or liver function tests may be needed. Treatment and prognosis: Patients with
alpha-thalassemia minor and beta-thalassemia minor will have a normal life expectancy.
With beta-thalassemia major life expectancy is decreased with few living to puberty
or beyond. With hemoglobin H disease the outlook is dependent on the clinical
course and the state of the liver and spleen. With severe splenomegaly or when
the anemia is severe, a splenectomy (removal of the spleen) may be required. It
may also reduce the amount of transfusions required. With children who have beta-thalassemia
major as few transfusion as possible should be give to avoid iron overload. However,
for children who have severe anemia a certain amount of transfusions may be beneficial
to suppress the abnormal blood cell formation of the bone marrow. An ongoing chelation
therapy program will prevent the toxic effects of excess iron on heart and liver
by removing it. Stem cell transplantation has been done successfully in a few
cases, but this is complicated by finding the right histocompatibility match,
the mortality of the procedure (about 5 to 10%) and the need for ongoing surveillance
of the immune system (immunosuppressive therapy) following the procedure. Eventually
gene therapy will likely be developed.
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