thalassemia

Introduction

a group of inherited conditions that cause defective production of haemoglobin
the most common is beta thalasemia which is autosomal recessive and thus exists in two forms:
- thalassemia minor - heterozygous trait mild form with mild reduction in Hb beta chain production and mild anaemia
- thalassemia major - homozygous severe form with severe reduction in Hb beta chain production
alpha thalassemia results in defective production of the alpha chain of Hb

conveys some protection against malaria hence the gene is primarily found in ethnic groups where historically malaria has been endemic
- “Thalassemia belt”: Mediterranean region, parts of Africa, Europe, the Middle East, and Southeast Asia
- the gene has been identified in a hunter-gatherer Vietnamese man 7000yrs ago suggesting malaria was an issue in SE Asia before farming practices commenced¹⁾
- malaria was once endemic in the Meditteranean Sea region hence the gene is common in Italian and Greeks (this was the inspiration for the naming of this condition - Greek thalassa for sea and -emia, meaning the blood)
- 3.7% of the population of India have the trait and India accounts for 10% of the global incidence of thalassemia major

whilst it does cause mild microcytic anaemia it does not usually need Rx and does not respond to iron therapy
if both parents have beta thalasemia minor they have a 25% chance of having a thalassemia major child and thus early antenatal tests to detect this are usually advised.

babies are protected as they utilise fetal Hb which is made from alpha and gamma chains and do not rely on the beta chain gene
the condition becomes manifest in the 1st year of life as fetal Hb wanes resulting in:
- severe anaemia compunded by haemolytic anemia
- irritability
- growth retardation
- hepatosplenomegaly with jaundice
primary treatment is continued blood transfusions and management of subsequent iron overload
some may benefit from bone marrow or stem cell transplants
gene therapy with insertion of a normal beta Hb gene is a potential future treatment

¹⁾