In addition to the deletion of genetic instructions, alterations can occur with each copying of the sets of genes. These are known as mutations and they can further affect the symptoms of thalassemia. Sometimes the deletion of nearby genes can also affect the outcome of thalassemia. Therefore for some patients, treatment and prognosis may not be accurate due to the difficulty in determining whether someone is homozygous or heterozygous and further genetic testing is needed. However, more more and more mutations are being catalogued around the world which is helping us understand how to better treat patients.
As a result of demographic changes and global migrations, many variant hemoglobins, which were previously limited to certain areas, now have spread worldwide, including to North America. There are over 200 hemoglobin beta (HBB) mutations that have been identified that with combinations of the alleles(genes) cause β-thalassemia, and 5 mutations that are responsible for the α-thalassemia genotype [1].
Many of these mutations can be co-inherited. These range from thalassemia with no adverse effects to those that produce diseases requiring treatment. Patients should consult with a hematologist for information on diagnoses and management of variant hemoglobins for the latest treatments.
Some of the disorders are listed with their corresponding phenotype:
| DISORDER NAME | PHENOTYPE |
| Hemoglobin M | Bluish cast to skin, mucous membranes, and underneath their fingernails |
| DISORDER NAME | PHENOTYPE |
| Hemoglobin S (HbSC) | Anemia and episodes of pain and other severe complications. |
| DISORDER NAME | PHENOTYPE |
| Hemoglobin E (HBE) | Most commonly found in the people of Southeast Asia. Can be as severe as β-thalassemia major. |
| DISORDER NAME | PHENOTYPE |
| Hemoglobin C (HbC) | More common in people of West African Descent. Chronic anemia, shortness of breath, fatigue, delayed growth and development in children, jaundice of the eyes and skin. |
| DISORDER NAME | PHENOTYPE |
| Combination of Hemoglobin S/b-thalassemia (HbSBetaThal disease) | Anemia, serious medical complications. |
| DISORDER NAME | PHENOTYPE |
| Hemoglobin H-Constant Spring disease (α-thalassemia genotype) | Sometimes requires regular transfusions. |