Is homozygosity in genetic testing for severe thalassemia severe?

The result of genetic testing for thalassemia, which shows homozygosity, may indicate severe thalassemia, but it may also be intermediate or mild. It is necessary to make a comprehensive judgment based on the specific genotype and clinical manifestations. Thalassemia can be classified into alpha thalassemia and beta thalassemia based on the type and severity of genetic defects, with homozygous or compound heterozygous mutations potentially leading to severe thalassemia. If severe thalassemia is caused by homozygous mutations in the β - globin gene (such as β 0/β 0 or β+/β+), it usually manifests as severe β - thalassemia. The child develops progressive anemia, hepatosplenomegaly, and developmental delay 3-6 months after birth, requiring regular blood transfusions and iron removal therapy. Some patients may require hematopoietic stem cell transplantation. Common mutation types include CD41-42, IVS-II-654, etc.

2. Intermediate thalassemia

Some homozygotes (such as β+/β+) or compound heterozygotes (such as β 0/β+) may present as intermediate thalassemia, with mild but more severe symptoms than the specific type, and intermittent anemia may occur. Some patients may require intermittent blood transfusions, and symptoms may worsen during infection or pregnancy. Hemoglobin H disease (--/- α 3.7) also belongs to this category.

3. Mild thalassemia

α - thalassemia homozygotes (- α 3.7/- α 3.7 or - α 4.2/- α 4.2) are usually mild, manifested as mild anemia or no clinical symptoms. Blood routine shows small cell hypochromic anemia, hemoglobin electrophoresis shows normal or mild decrease in HbA2, and generally do not require special treatment.

4. Genotyping analysis

requires specific mutation sites to be identified through gene sequencing. Common detection methods include PCR reverse dot hybridization, gap PCR, MLPA, etc. Homozygous of the Southeast Asian deletion type (SEA) can lead to fetal edema syndrome, while homozygotes of β E/β E may exhibit intermediate thalassemia in Southeast Asia.

5. Clinical management

After diagnosis, it is necessary to evaluate the degree of anemia, iron overload, and organ damage. For severe patients, it is recommended to receive blood transfusions every 2-4 weeks to maintain Hb>90g/L, combined with iron removal treatments such as Deferasirox dispersible tablets and Deferiptyline injection. Couples of childbearing age should undergo prenatal diagnosis to avoid the birth of fetuses with severe thalassemia. Patients with thalassemia should avoid blind supplementation of iron supplements and regularly monitor serum ferritin and liver function. Intermediate and severe patients need to prevent infection and be vaccinated with pneumococcal vaccine and hepatitis B vaccine. Pay attention to balanced nutrition in diet, increase foods rich in folic acid such as animal liver and dark green vegetables in moderation, and avoid a high oxalate diet that affects the effectiveness of iron chelators. It is recommended to review blood routine and iron metabolism indicators every 3-6 months, and if necessary, perform cardiac MRI to evaluate iron deposition.