[1] Symptoms include tiredness, pallor, bone problems, an enlarged spleen, jaundice, pulmonary hypertension, and dark urine.

[17] The specific alpha and beta-like chains that are incorporated into hemoglobins are highly regulated during development:[18] Symptoms depend on the type and severity of thalassemia.

[24] Beta thalassemia symptoms typically begin to show during the first six months of life, as the body winds down production of fetal hemoglobin HbF.

[21] If thalassemia is untreated or undetected in the infant, this can lead to developmental issues such as slowed growth, delayed puberty, bone abnormalities, and intellectual impairment.

This expansion is a compensatory response to the damage caused to red blood cells by the imbalanced production of globin chains.

Expansion of the bone marrow in the developing child leads to a distinctive facial shape often referred to as "Chipmunk facies".

Symptoms include an irregular heartbeat, cardiomyopathy, cirrhosis of the liver, hypothyroidism, delayed puberty and fertility problems, brittle and deformed bones, and an enlarged spleen.

[32][33] The spleen is the organ which removes damaged red blood cells from circulation; in thalassemia patients it is abnormally active, causing it to enlarge and possibly become hyperactive, a condition called hypersplenism.

Checking for hemoglobinopathies begins during pregnancy, with a prenatal screening questionnaire which includes, among other things, a consideration of health issues in the child's parents and close relatives.

[63][64] A routine heel prick test, in which a small sample of blood is collected a few days after birth, can detect some forms of hemoglobinopathy.

[73][74] Multiple blood transfusions lead to severe iron overload, as the body eventually breaks down the hemoglobin in donated cells.

More recently, it has become possible to use CRISPR gene editing technology to modify the patient's own HSCs in a way that increases production of functional beta-globin chains, leading to near normal levels of healthy hemoglobin.

[83] All stem cell treatments must involve myeloablation of the patients' bone marrow in order to remove HSCs containing the faulty gene.

[84][85] Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for both alpha and beta thalassemia.

Cells are ideally sourced from human leukocyte antigen matched relatives; the procedure is more likely to succeed in children rather than adults.

Since then, a number of patients have received bone marrow transplants from healthy matched donors, although this procedure has a high level of risk.

[88] In 2018 an unborn child with hydrops fetalis, a potentially fatal complication of alpha thalassemia, was successfully transfused in utero with her mother's stem cells.

Risks associated with HSCT can include graft-versus host disease, failure of the graft, and other toxicity related to the transplant.

[90] In one study of 31 people, the procedure was successful for 22 whose hemoglobin levels improved to the normal range, in seven the graft failed and they continued to live with thalassemia, and two died of transplantation-related causes.

In parallel with this, the person with thalassemia disease undergoes a myeloablation procedure (a form of chemotherapy) to destroy the remaining HSCs in their bone marrow.

Meanwhile the affected person undergoes myeloablative conditioning, after which the altered HSCs can be infused back, becoming engrafted in the bone marrow where they proliferate.

This results in a progressive increase in beta-globin synthesis which improves the balance of alpha and beta globins in all subsequent developing red blood cells.

[94] Exagamglogene autotemcel, sold under the brand name Casgevy, is a gene therapy for the treatment of transfusion-dependent beta thalassemia which induces increased production of fetal hemoglobin HbF.

The edit has the effect of increasing production of gamma globin, a component of fetal hemoglobin HbF, and thereby resolving the anemia.

If both have a concentration above 3.5% (diagnostic of thalassemia trait) they are referred to the local designated health post for genetic counseling.

With the exception of the Balearics, the major Mediterranean Islands, such as Sicily, Sardinia, Malta, Corsica, Cyprus, and Crete are heavily affected.

[108] The disease is also found in populations living in Africa, the Americas, and in Tharu people in the Terai region of Nepal and India.

[113] However, exact data on carrier rates in many populations are lacking, particularly in developing areas of the world known or expected to be heavily affected.

[115] Rudolf Von Jaksch in 1889 first described “anaemia leucaemic infantum” as a form of chronic anemia in children which combined with an enlarged spleen, and abnormal size and shape of the red blood cells.

[116] The first definitive identification of a thalassemia was in 1925 by Thomas Benton Cooley, an American pediatrician specialising in hematology and childhood anemias.