1. Thalassemia
The word is derived from a Greek word “thalassa” which means “the sea” and “emia” meaning related to blood.
The Disease is more common in populations in the geographic belt from south east Asia to Africa.
It is caused by defects in the globin gene and it is the most common monogenic disease.
More than 200 mutations are described and the defects are inherited in an autosomal recessive manner.
The major Hb is HbA which comprise of 90% of total Hb in children beyond 1 year of age. Hb for foetal life is HbF. And HbA2 comprises of 2-3% of total Hb.
- HbA constitutes of 2 alpha chains and 2 beta chains.
- HbF constitutes of 2 alpha chains and 2 gamma chains.
- HbA2 constitutes of 2 alpha chains and 2 delta chains.
Thalassemias are inherited disorders of Hb synthesis that result from an alteration in the rate of globin chain production. A decrease in the rate of globins impedes Hb synthesis and creates an imbalance with normally produced globin chains.
It is because 2 types of chains (alpha and non-alpha) pair with each other at a ratio close to 1:1 to form normal Hb.
An excess of normally produced type is present and accumulates in the cell as an unstable product, leading to the early destruction of red cell.
◾Symptoms-
Severe pallor, hepatosplenomegaly, Mild- moderate Jaundice may occur due to Liver dysfunction.
Symptoms of severe anemia such as intolerance to exercise, irritability, heart murmur, Ineffective erythropoiesis , Bony abnormalities may occur.
◾Spectrum of Disease-
- Beta- thalassemia trait- elevated levels of HbA2 or HbF or both due to abnormal Hb.
- Thalassemia intermediate- It is due to compound heterozygous states, does not require regular blood transfusion.
- Thalassemia major- characterized by transfusion dependent anaemia. Organomegaly may occur.
- Associated variants- HbE or Beta Thalassemia
◾Diagnosis- CBC (Complete Blood Count), peripheral blood film examination. MCV and MCH decrease while the reticulocyte count elevates and leukocytosis.
Differential diagnosis with hyperchromic, microcytic anaemia.
◾Management- Genetic counseling, Blood transfusion at early age, iron chelating agents and Hemopoietic stem cell transplantation.
2. Sickle cell Anaemia
Autosomal recessive disease that results from the substitution of valine for glutamic acid at position 6 of Beta- globin gene.
Patients who are homozygous for the Hb S gene have sickle trait.
🔻Gene frequency in India – 4.3%
Sickle red blood cells are less deformable
and obstruct microcirculation, resulting in tissue of tissue hypoxia.
These red blood cells are rapidly hemolyzed and have life span of 10-20 days.
◾Clinical features- Pain is the most common presentation of vaso-occlusive crisis.
Presentation with pain suggest acute chest syndrome if pleuritic in nature & arthritis of osteomyelitis if joints or bone are involved.
Usual presentation in a young child is icterus due to elevated unconjugated bilirubin, pallor and mild splenomegaly
Disease may manifest as febrile illness.
children are prone to pneumococcal, salmonella and other bacterial infections.
◾Crisis–
- Vaso-occlusive Crisis- microcirculation is obstructed
- Acute chest syndrome
- Sequestration Crisis- Sickle cells block splenic outflow
- Aplastic Crisis- Bone marrow stops producing RBCs.
◾Diagnosis- Anaemia and Thrombocytosis, Leukocytosis, Rise in WBC count, Peripheral smear(sickle shaped RBCs found).
Sickling test will establish presence of sickle Hb.
◾Management-
- Hydration and analgesia in pain crisis.
- Blood transfusion in Aplastic Crisis and acute sequestration crisis
- Oxygen supplementation