Beta-thalassemia is generally grouped into three levels of severity, and the level a person falls into depends on how much functional beta-globin their particular combination of HBB variants still allows.

• Beta-thalassemia major, also called Cooley’s anaemia. This is the most severe form, usually noticed between six and twenty-four months of age as the protective haemoglobin present at birth naturally declines. Affected infants develop pale skin from severe anaemia, poor weight gain, slowed growth, mild yellowing of the skin and eyes called jaundice, and an enlarged liver and spleen as these organs try to compensate for the shortage of healthy red blood cells. Without regular treatment, bone changes from marrow expansion and severe, life-threatening anaemia follow.
• Beta-thalassemia intermedia. This form causes a more variable, generally milder anaemia that does not require regular transfusions in early childhood, though needs can increase later in life. Individuals may still develop jaundice, gallstones, slow-healing leg ulcers, bone deformities, an enlarged spleen, and, over time, elevated blood pressure in the lungs called pulmonary hypertension.
• Beta-thalassemia trait, also called beta-thalassemia minor. This describes carriers, who have one altered and one working copy of the HBB gene. Most carriers have no symptoms at all and are unaware of their status until tested, though some have a very mild anaemia.

Diagnosis usually begins with a complete blood count, which typically shows small, pale red blood cells and anaemia of a severity that fits the person’s symptoms. A close look at the blood under a microscope often shows red blood cells of unusual shapes and sizes. Because this pattern can look similar to iron-deficiency anaemia, which is also common in India, a haemoglobin analysis test — either haemoglobin electrophoresis or high-performance liquid chromatography (HPLC) — is essential to tell the two apart and confirm beta-thalassemia. This test measures the different types of haemoglobin in the blood and typically shows reduced or absent normal adult haemoglobin along with elevated levels of two other forms, haemoglobin A2 and hemoglobin F, in beta-thalassemia. Genetic testing of the HBB gene then confirms the diagnosis, identifies the exact variants involved, and is an important step before testing other family members or planning future pregnancies, discussed next. It is worth noting that thalassemia trait is sometimes mistaken for iron deficiency and treated with iron supplements unnecessarily, so confirming the correct diagnosis with iron studies and haemoglobin analysis matters for appropriate care.