In a 9‑year‑old child with normal hemoglobin, borderline low mean corpuscular volume, normal red cell distribution width, elevated total iron‑binding capacity, normal ferritin, low‑normal serum iron (88 µg/dL) and transferrin saturation of 20 %, what is the most likely diagnosis and what is the appropriate next step in management?

Diagnosis: Early Iron Deficiency Without Anemia

This 9-year-old child most likely has early iron deficiency (ID) without anemia, and the appropriate next step is to obtain hemoglobin electrophoresis to rule out beta-thalassemia trait, followed by therapeutic iron supplementation if thalassemia is excluded. 1, 2

Diagnostic Interpretation

The laboratory pattern strongly suggests iron deficiency:

• Elevated TIBC with borderline low TSAT (20%) indicates insufficient circulating iron available for erythropoiesis, as TSAT <20% is typically diagnostic of iron deficiency 3
• Borderline low MCV with normal hemoglobin represents early iron-restricted erythropoiesis before frank anemia develops 3
• Normal ferritin does not exclude iron deficiency in this context, as ferritin can remain falsely normal in the presence of subclinical inflammation or during the transition from iron depletion to iron-deficient erythropoiesis 3
• Normal RDW is reassuring but does not exclude early ID, as RDW elevation occurs later in the progression of iron deficiency 3

Critical Differential: Beta-Thalassemia Trait

Before initiating iron therapy, you must rule out beta-thalassemia trait, as both conditions present with microcytosis but require completely different management:

• Order hemoglobin electrophoresis or HPLC to measure HbA2 levels; elevated HbA2 >3.5% confirms beta-thalassemia trait 1, 2
• Key distinguishing features favoring thalassemia trait include disproportionately low MCV relative to mild or absent anemia, elevated RBC count, and normal RDW 1, 2
• Both conditions can coexist, and iron deficiency can mask thalassemia trait by lowering HbA2 below the diagnostic threshold 2

Recommended Management Algorithm

Step 1: Complete the Diagnostic Workup

• Check RDW if not already done, as elevated RDW strongly suggests iron deficiency over thalassemia trait 1, 2
• Obtain hemoglobin electrophoresis to definitively exclude beta-thalassemia trait before starting iron supplementation 1, 2
• Consider checking CRP or ESR to assess for occult inflammation that could falsely normalize ferritin 3

Step 2: Initiate Iron Supplementation

If hemoglobin electrophoresis is normal (HbA2 <3.5%):

• Start therapeutic oral iron at 3-6 mg/kg/day of elemental iron to correct the documented iron deficiency 1, 2
• Reassess hemoglobin and iron parameters after 8-12 weeks to confirm response 1
• Investigate underlying causes including dietary inadequacy, rapid growth demands, occult blood loss, or malabsorption 2, 4

Step 3: If Thalassemia Trait is Confirmed

• Provide genetic counseling and recommend partner screening if family planning is relevant 1
• Treat coexisting iron deficiency with the same iron supplementation regimen, but expect only partial improvement (hemoglobin may increase but MCV will remain low) 1
• Avoid chronic iron supplementation beyond correction of deficiency, as thalassemia carriers do not benefit from ongoing iron and risk iron overload 1

Critical Pitfalls to Avoid

• Do not dismiss iron deficiency based on normal ferritin alone, especially in a child with borderline low MCV and low TSAT 3
• Do not start empiric iron therapy without ruling out thalassemia trait, as this can lead to unnecessary long-term iron supplementation in a child who doesn't need it 1, 2
• Do not assume normal hemoglobin excludes clinically significant iron deficiency, as iron-deficient erythropoiesis can occur before anemia develops, potentially affecting neurodevelopment 3, 4

Additional Considerations

Soluble transferrin receptor (sTfR) measurement could be considered if the diagnosis remains unclear after initial workup, as sTfR is elevated in iron deficiency but remains normal in thalassemia trait and functional iron deficiency 3