Two-and-a-half-year-old Pratik (name changed), a normal, seemingly healthy child, was visiting his paediatrician for a regular check-up. The paediatrician thought that Pratik was pale looking and requested a complete blood count investigation to be done. The results indicated low haemoglobin levels, high RBC counts, and high red cell distribution width. In addition, cells were small, indicative of microcytic hypochromic anaemia. Pratik was therefore suspected to have iron deficiency anaemia and serum iron studies were done. These also showed evidence of iron deficiency and Pratik was started on iron supplements. At the one month follow up, his repeat complete blood counts showed improved haemoglobin levels. However, the RBC count was still high and the microcytosis was severe. He was referred to Dr Swati Kanakia, Paediatric Hemato-Oncologist, Lilavati Hospital and Research Center, Mumbai. Based on complete blood count results, Dr Kanakia suspected Pratik may have thalassemia minor.
Thalassemia is a genetic disorder in which the body produces low levels of functional haemoglobin. Haemoglobin is made up of alpha and beta chains. Depending on which protein levels are affected, a patient can have either alpha thalassemia or beta thalassemia. Based on the severity of clinical features, alpha thalassemia can be classified as a silent carrier, thalassemia trait, haemoglobin H disease, or hydrops fetalis. Beta thalassemia can be classified as thalassemia minor, thalassemia intermediate or thalassemia major. Alpha thalassemia is caused due to mutations in the HBA1 or HBA2 gene on chromosome
16, while beta thalassemia is caused due to mutations in the HBB gene on chromosome 11.
Haemoglobin electrophoresis is a low cost, easily available test which takes only 24 hours and can rapidly confirm the diagnosis of beta thalassemia. It is therefore typically done first. However, alpha thalassemia cannot be detected by this method and requires genetic testing. Results on Pratik’s blood sample ruled out beta thalassemia. However, because of the persistent high RBC count and severe microcytosis, Dr Kanakia suggested genetic testing to look for mutations in the alpha haemoglobin chain. Genetic test results revealed a mutation in the HBA1 gene, confirming that Pratik was a silent carrier for alpha thalassemia. Similar genetic tests done on Pratik’s mother showed that she was also a silent carrier. However, her complete blood count results were absolutely normal, and she showed no signs of haemoglobin deficiency or microcytic anaemia. The reason for Pratik’s iron deficiency turned out to be because of his diet as he was predominantly on milk. Had the doctors not pursued the reason for his microcytic anaemia, Pratik and his mother’s alpha thalassemia silent carrier status might have gone undetected.
With genetic testing conveniently available, screening for thalassemia should be considered in patients who seem to have iron deficiency anaemia with microcytic anaemia and high RBC counts. Correct diagnosis can prevent incorrect supplementation with iron and avoid excessive investigation in an attempt to treat ‘suspected’ refractory iron deficiency. Further, patients like Pratik, who are silent carriers, can be counselled so as to prevent thalassemia cases later.
In India, beta thalassemia is much more prevalent than alpha thalassemia and is a major public health concern. Because of the need for genetic testing to confirm alpha thalassemia, it is likely that alpha thalassemia is under-reported as well. “The main goal is to prevent the birth of children with thalassemia major”, says Dr Kanakia. If Pratik’s father was also a carrier for alpha thalassemia, Pratik’s siblings could have a much more severe version of thalassemia that may require regular blood transfusions and even bone marrow transplantation. Treatment can be very expensive and heavily dependent on the availability of suitable donors for bone marrow transplantation. It is therefore important to screen for carriers of alpha and beta thalassemia. This will help in identifying future pregnancies that need to undergo prenatal testing to rule out severe forms of thalassemia.
In an effort to aid patient education and prevent thalassemia major cases, Dr Kanakia and Kanakia Health Care have created a programme called Stop Thal, Screening for Thalassemia and Opting for Prevention. The programme helps one estimate the chances of having a completely normal, thalassemia minor, or thalassemia major child and would increase awareness amongst thalassemia patients and prove to be useful in reducing thalassemia major incidents.