Clinical Presentation of Thalassemia Major in Children Under 2 Years
Children with thalassemia major are healthy at birth but develop severe anemia with pallor, failure to thrive, and hepatosplenomegaly between 1-2 years of age as fetal hemoglobin production declines. 1
Timing of Symptom Onset
- Infants are asymptomatic at birth because fetal hemoglobin (HbF, composed of α2γ2 chains) does not require β-globin chains for function 1
- Clinical manifestations emerge at approximately 1-2 years of age (mean age at presentation 13.2 ± 9.7 months) as the physiologic switch from fetal to adult hemoglobin occurs 1, 2
- Nearly two-thirds of children present before 1 year of age, with approximately 40% having symptoms for 3 months prior to diagnosis 2
Cardinal Clinical Features at Presentation
Hematologic Manifestations
- Severe pallor is the most prominent presenting sign 2
- Approximately 40% present with hemoglobin <5.0 g/dL, indicating severe anemia 2
- The anemia is profound and progressive without transfusion support 3
Growth and Development
- Failure to thrive is a hallmark feature at presentation 2
- Growth retardation becomes evident in early childhood without adequate transfusion therapy 4
Organomegaly
- Hepatosplenomegaly develops during infancy as a consequence of extramedullary hematopoiesis and hemolysis 3, 2
Skeletal Changes
- Skeletal aberrations may develop in early childhood due to bone marrow expansion attempting to compensate for ineffective erythropoiesis 4
Pathophysiologic Basis of Clinical Presentation
- The condition results from homozygosity or compound heterozygosity for β-thalassemia mutations causing severe reduction (β+) or complete absence (β0) of functional β-globin chain synthesis 1
- Globin chain imbalances result in hemolysis and impaired erythropoiesis, leading to the severe anemia 4
- Without treatment, the natural history is fatal in early childhood 3
Critical Diagnostic Considerations
- Newborn screening in the United States detects large amounts of fetal hemoglobin, triggering further investigation for thalassemia 5
- Many children receive blood transfusions prior to establishment of the definitive diagnosis 2
- Thalassemia major is defined by the requirement for more than 8 transfusion events per year in adults, but children require regular transfusions from the time of diagnosis 1
Common Pitfall to Avoid
Do not delay diagnosis in infants presenting with severe anemia and hepatosplenomegaly between 6-24 months of age—this presentation pattern is classic for thalassemia major and requires immediate hemoglobin electrophoresis and genetic testing 2. Approximately 40% of families report symptoms for 3 months before diagnosis, representing a critical window of delayed recognition 2.