Author: Julie Routhieaux, RN, PCNS | Pediatric Clinical Nurse Specialist, Division of Hematology and Oncology | Sickle Cell Disease Program
Column editor: Amita R. Amonker, MD | Pediatric Hospitalist | Assistant Professor of Pediatrics, UMKC School of Medicine
The term hemoglobinopathy refers to a genetic defect that affects the amount or structure of one or more of the globin chains in the hemoglobin molecule. These defects are autosomal recessive genetic conditions, meaning the child inherits an abnormal hemoglobin gene from each of its parents, except in patients with trait conditions where only one abnormal hemoglobin gene is passed down. One of the main types of hemoglobinopathies is thalassemia.
Typical healthy hemoglobin molecules (HgbA) have two alpha chains and two beta chains. Thalassemia refers to a group of disorders in which the alpha-to-beta-chain ratio in the hemoglobin molecule is abnormal. This causes unpaired chains to precipitate, leading to destruction of red blood cells and resulting in hemolytic anemia. There are two main types of thalassemias—Alpha and Beta.
Alpha thalassemia occurs when a gene or genes related to alpha globin genes are missing or mutated. Alpha thalassemias occur most often in people of Southeastern Asia, Middle Eastern, Chinese and African descent.
Alpha (0) thalassemia occurs when the genetic mutation causes both alpha chains to be absent (all four alpha globin genes—two from each parent—are mutated or missing) and the patient is unable to make Hgb A. This is also called hydrops fetalis, and is generally fatal after birth.
Alpha thalassemia major (Hemoglobin H disease) occurs when three of the alpha globin genes are missing or mutated. Bones can be affected, including changes to the cheeks, forehead and jaw. Jaundice and splenomegaly may also occur.
Alpha thalassemia minor (trait) occurs when one or two of the globin genes are missing or mutated. Typically, these patients will be asymptomatic, though patients with alpha thalassemia minor/trait may have mild microcytic anemia. Patients should be counseled regarding their carrier status.
Beta thalassemia is an inherited hemoglobinopathy in which the production of one or both beta globin chains is impaired. The severity of clinical symptoms depends on the degree of impairment in beta globin production. Beta thalassemias are most often seen in patients of Mediterranean and Asian descent.
Beta0 thalassemia (Thalassemia major; Cooley’s Anemia) refers to mutations where beta globin genes are missing. These patients are unable to make any hemoglobin A. They experience severe hemolytic anemia, which can be fatal, and are transfusion-dependent.
Thalassemia Intermedia is a less severe type of thalassemia caused by mutations in both beta globin genes. Symptoms are less severe and regular transfusion therapy is not generally needed for this disease.
Beta thalassemia minor (also called beta thalassemia trait) occurs in patients with a beta thalassemia mutation combined with a normal beta globin gene. These individuals have mild anemia and few symptoms.
Diagnosis: There are multiple ways to identify hemoglobinopathies. All children born in the United States are tested via newborn screening for hemoglobinopathies before they are discharged from the hospital. If abnormal results are detected, confirmatory testing should be completed with a blood sample sent for hemoglobin electrophoresis, along with a CBC and reticulocyte count. It is helpful for this testing to be completed by the primary care provider before a referral is made.