Hematology Oncology · Year 2 · from Hematology Oncology

Case 2: Beta-Thalassemia Major

Patient Presentation

Demographics: 8-year-old male of Mediterranean descent

Chief Complaint: Routine transfusion clinic visit

History of Present Illness: The patient was diagnosed with beta-thalassemia major at 18 months of age when he presented with severe anemia and failure to thrive. He has been on a chronic transfusion program, receiving packed red blood cells every 3-4 weeks to maintain pre-transfusion hemoglobin above 9 g/dL. He is on deferasirox for iron chelation. His parents are concerned about his short stature compared to peers.

Physical Examination:

  • Vital signs: BP 100/65, HR 90, RR 18, Temp 36.8C
  • General: Small for age, appears younger than stated age
  • HEENT: Frontal bossing, prominent maxillary bones (chipmunk facies)
  • Cardiac: Grade II/VI systolic murmur
  • Abdomen: Hepatomegaly (4 cm below costal margin), splenomegaly (6 cm below costal margin)
  • Growth: Height and weight below 5th percentile

Workup and Results

Complete Blood Count (pre-transfusion):

  • Hemoglobin: 8.8 g/dL
  • MCV: 68 fL
  • RDW: 22%
  • Reticulocyte count: 4%

Hemoglobin Electrophoresis:

  • HbF: 95%
  • HbA2: 5%
  • HbA: 0%

Iron Studies:

  • Ferritin: 2,400 ng/mL (elevated despite chelation)
  • Transferrin saturation: 85%

Monitoring Labs:

  • Cardiac MRI T2*: 15 ms (borderline cardiac iron loading)
  • Liver iron concentration: 8 mg/g dry weight (elevated)

Genetic Testing:

  • Homozygous for beta-zero thalassemia mutation

Diagnosis

Beta-Thalassemia Major (Cooley's Anemia) with Iron Overload

Key features:

  • Absent beta-globin production (beta-zero/beta-zero)
  • Transfusion-dependent anemia
  • Iron overload requiring chelation
  • Classic skeletal changes from marrow expansion
  • Growth delay from chronic anemia and iron overload endocrinopathy

Treatment Plan

  1. Transfusion therapy:
  • Continue regular transfusions every 3-4 weeks
  • Target pre-transfusion Hgb 9-10.5 g/dL
  • Use leukoreduced, phenotypically matched blood
  1. Iron chelation intensification:
  • Increase deferasirox dose
  • Consider combination therapy (deferasirox + deferoxamine) for cardiac iron
  • Target ferritin < 1,000 ng/mL, cardiac T2* > 20 ms
  1. Monitoring:
  • Annual cardiac MRI T2* for cardiac iron
  • Annual liver MRI for hepatic iron
  • Endocrine evaluation (growth hormone, thyroid, glucose)
  • DEXA scan for bone density
  1. Curative options:
  • HLA typing for potential matched sibling donor transplant
  • Discuss gene therapy clinical trials

Teaching Points

  1. Beta-thalassemia major presents in infancy as HbF declines and beta-chain deficiency manifests
  2. Without transfusion, severe anemia triggers massive marrow expansion causing skeletal deformities
  3. Chronic transfusion leads to iron overload - the major cause of morbidity without chelation
  4. Cardiac iron (measured by T2* MRI) is the critical determinant of survival
  5. Allogeneic stem cell transplant is curative in young patients with matched donors
  6. Gene therapy (betibeglogene autotemcel) now FDA-approved as curative option

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