Causes of Microcytic Hypochromic Anemia in Children
Iron deficiency anemia is by far the most common cause of microcytic hypochromic anemia in children, accounting for approximately 77% of cases, followed by thalassemia trait (13.5%), with both conditions coexisting in 5-7% of patients. 1
Primary Causes
Iron Deficiency Anemia (Most Common)
- Iron deficiency represents approximately 80% of all microcytic anemias worldwide and is the predominant cause in pediatric populations. 2
- Common underlying mechanisms include:
Thalassemia Trait
- Beta-thalassemia trait accounts for 13.5% of microcytic anemia cases in children and must always be considered, particularly in regions where it is endemic. 1
- Alpha-thalassemia gene mutations also occur but are less frequent 1
- This diagnosis is critical for genetic counseling and avoiding unnecessary iron therapy 5
Genetic Disorders of Iron Metabolism and Heme Synthesis (Rare)
- Despite very low prevalence, hereditary disorders must be considered when standard iron deficiency treatment fails. 5
- Specific genetic conditions include:
- ALAS2 defects (X-linked sideroblastic anemia): Responds to pyridoxine (vitamin B6) 50-200 mg daily 4, 6
- SLC11A2 (DMT1) defects: Present with microcytic anemia and increased transferrin saturation 6
- TMPRSS6 defects (IRIDA): Causes resistance to oral iron, requiring intravenous iron 4
- STEAP3 defects: Require erythrocyte transfusions combined with erythropoietin 4
- SLC25A38 defects: May require hematopoietic stem cell transplantation as curative option 4, 6
- Hypotransferrinemia: Characterized by low transferrin, low serum iron, high ferritin 6
Anemia of Chronic Disease
- Functional iron deficiency occurs in chronic inflammatory conditions where iron utilization is blocked as a nonspecific defense mechanism. 2
- This is less common in children but must be differentiated from true iron deficiency 4
Diagnostic Differentiation Algorithm
Initial Laboratory Assessment
- A low MCV with RDW >14.0% suggests iron deficiency anemia, while a low MCV with RDW ≤14.0% suggests thalassemia minor. 4
- However, one study found RDW was not significantly different between iron deficiency and beta-thalassemia trait groups 1
Key Discriminating Tests
- Serum ferritin <15 μg/L indicates absent iron stores; <30 μg/L indicates low body iron stores, with a cut-off of 45 μg/L providing optimal sensitivity and specificity. 4
- Mentzer index (MCV/RBC count) has 100% sensitivity and 69.4% specificity for detecting beta-thalassemia trait, with 100% negative predictive value. 1
- Transferrin saturation is more sensitive than hemoglobin alone for detecting iron deficiency 4
- Serum iron, TIBC, and ferritin are significantly different between iron deficiency and beta-thalassemia trait 1
When to Suspect Genetic Disorders
- Failure to respond to adequate oral iron therapy after 4 weeks warrants investigation for genetic disorders or alternative diagnoses. 7
- Extremely low MCV with mild anemia strongly suggests genetic disorder rather than simple iron deficiency 6
- Normal or elevated ferritin with microcytic anemia suggests anemia of chronic disease or genetic disorder 7
- Family history of refractory microcytic anemia 7
Critical Pitfalls to Avoid
- Do not assume all microcytic anemia is iron deficiency—thalassemia and sideroblastic anemia must be differentiated to avoid unnecessary iron therapy and provide appropriate genetic counseling. 4, 5
- Overlooking combined deficiencies is common: iron deficiency can coexist with thalassemia trait in 5-7% of children with microcytic anemia. 7, 1
- Stopping iron therapy when hemoglobin normalizes leads to relapse; continue for at least 3 months after correction to replenish iron stores 4, 7