Thalassemia

1. Presented By- Dr. Armaan Singh

2. Thalassemia is a form of inherited autosomal recessive blood
disorders characterized by abnormal formation of haemoglobin. The
abnormal haemoglobin formed results in improper oxygen transport
and destruction of red blood cells.[1]
Thalassemia is caused by variant
or missing genes that affect how the body makeshemoglobin, the
protein in red blood cells that carries oxygen. People with
thalassemia make less hemoglobin and have fewer circulating red
blood cells than normal, which results in mild or severe anemia.
Thalassemia will be present as microcytic anemia. There are two α
genes on each chromosome 16, giving α thalassaemia the unique
feature of gene duplication. There is only one β-globin gene on
chromosome 11.

3. α thalassaemia
*Normal: genotype α,α/α,α.
*α+ thalassaemia heterozygous (genotype α,-/α,α): borderline haemoglobin level and
mean corpuscular volume (MCV), low mean corpuscular haemoglobin (MCH); clinically
asymptomatic.
*α+ thalassaemia homozygous (genotype α,-/α,-): slightly anaemic, low MCV and MCH;
clinically asymptomatic.
*αo thalassaemia heterozygous (genotype α,α/,--): slightly anaemic, low MCV and MCH;
clinically asymptomatic.
*HbH disease (genotype α,-/-,-): HbH. Anaemic, very low MCV and MCH; splenomegaly,
variable bone changes.
*α thalassaemia major (genotype -,-/-,-): Hb Bart's. Severe non-immune intrauterine
haemolytic anaemia. Hb Bart's hydrops fetalis, usually fatal.

4. β thalassaemia
*Normal: genotype β2/β2.
*β-thalassaemia trait (genotype -/β2): HbA2 >4%. Slightly anaemic, low MCV and MCH;
clinically asymptomatic.
*β thalassaemia intermedia (genotype -/βo or β+/β+): high HbF, variable. Anaemic
(symptoms usually develop when the haemoglobin level remains below 7.0 g/dL), very
low MCV and MCH; splenomegaly, variable bone changes, variable transfusion
dependency.
*β thalassaemia major (genotype -o/-o): HbF >90% (untransfused). Severe haemolytic
anaemia, very low MCV and MCH; hepatosplenomegaly, chronic transfusion dependency.

5. Signs
*Presentation varies with severity. Thalassaemia minor rarely has any physical
abnormalities with haemoglobin ≥9 g/dL. In patients with the severe forms, the findings on
physical examination vary widely depending on how well the disease is controlled. In
severe, untreated cases there may be:
*Hepatosplenomegaly.
*Bony deformities (frontal bossing, prominent facial bones, and dental malocclusion).
*Marked pallor and slight to moderate jaundice.
*Exercise intolerance, cardiac flow murmur or heart failure secondary to severe anaemia.
*These features are absent in well-treated patients but there are often still problems:
*Growth restriction is common even with well-controlled chelation therapy.
*Iron overload can cause endocrinopathy with diabetes, thyroid, adrenal and pituitary
disorders.

6. Differential diagnosis
*Other causes of microcytic anaemia - eg, iron-deficiency
anaemia, sideroblastic anaemia and anaemia of chronic disease.
*Acute leukaemia may require bone marrow aspiration to
differentiate.
*Rhesus incompatibility is rare now and post-mortem haemoglobin
electrophoresis should differentiate in cases of hydrops fetalis.
*Diamond-Blackfan syndrome is a rare congenital cause of erythroid
aplasia. It causes a severe normochromic, macrocytic anaemia usually
in infancy and is often associated with craniofacial or upper limb
anomalies.

7. Investigations:
*FBC shows a microcytic, hypochromic anaemia (β-thalassaemia carrier status is often
confused with iron deficiency due to reduced MCV and MCH). In the severe forms of
thalassaemia, the haemoglobin level ranges from 2-8 g/dL. White blood cell (WBC) count is
usually elevated from the haemolytic process. Platelet count may be depressed in
splenomegaly.
*Serum iron level is elevated, with saturation as high as 80%. Ferritin is also raised.
*Haemoglobin electrophoresis usually reveals the diagnosis. Normal HbA2 is between 1.5
and 3.0% whilst HbA2 >3.5 % is diagnostic.:
*ECG and echocardiogram are used to monitor cardiac function.
*HLA typing is required where bone marrow transplantation is considered.
*Eye examinations, hearing tests and renal function tests are required in the monitoring of
desferrioxamine therapy. Bone marrow aspiration is sometimes needed at diagnosis to
exclude other conditions that may mimic thalassaemia major's presentation. Liver biopsy is
used to assess iron deposition and the degree of haemochromatosis.