What could explain low iron saturation, slightly low hemoglobin, low fasting insulin levels, and significantly elevated B12 levels in a child?

Laboratory Pattern Consistent with Iron Deficiency Despite Normal Ferritin

This child has functional iron deficiency (iron-deficient erythropoiesis) despite apparently adequate iron stores, as evidenced by the severely low iron saturation of 6% and low total iron of 19, which are the critical diagnostic findings here. 1

Understanding the Paradox

The ferritin level of 150 ng/mL appears normal or even elevated for an 8-year-old, but this does not exclude iron deficiency because:

• Ferritin is an acute phase reactant that can be falsely elevated by inflammation, infection, or chronic disease, masking true iron depletion 1
• The iron saturation of 6% is severely low (normal >20%), indicating insufficient iron is available for hemoglobin synthesis regardless of storage iron 1
• Total iron of 19 is markedly reduced, confirming inadequate circulating iron for erythropoiesis 1
• The hemoglobin of 12.3 g/dL is at the lower end of normal for an 8-year-old girl, suggesting early iron-deficiency anemia 2, 3

The Elevated B12 Level (1100 pg/mL)

The significantly elevated B12 without supplementation requires investigation for underlying pathology:

• Functional B12 deficiency can paradoxically present with high serum B12 but inadequate cellular utilization 4
• Liver disease can release stored B12 into circulation 4
• Myeloproliferative disorders (rare in children but possible) can elevate B12 4
• Renal dysfunction can impair B12 clearance 4

However, the most likely explanation in this context is that elevated B12 may be incidental or related to dietary intake of fortified foods, though the level of 1100 is unusually high without supplementation 4.

The Low Fasting Glucose and Insulin Pattern

The fasting blood sugar of 60 mg/dL with low insulin levels and A1c of 4.8% suggests:

• Reactive hypoglycemia or inadequate caloric intake, which could contribute to nutritional deficiencies 5
• The low A1c (4.8%) is artificially reduced due to the increased proportion of young red blood cells in iron deficiency, as immature erythrocytes have less time to accumulate glycosylated hemoglobin 5
• This pattern does NOT indicate diabetes but rather reflects the altered RBC population dynamics in iron deficiency 5

Diagnostic Approach

Order these specific tests to clarify the diagnosis:

• MCV and RDW to assess for microcytosis and red cell size variation (RDW >14% with low MCV confirms iron deficiency over thalassemia) 1
• Erythrocyte protoporphyrin (>80 µg/dL in children indicates iron-deficient erythropoiesis) 1
• C-reactive protein (CRP) or ESR to identify inflammation that could falsely elevate ferritin 1
• Methylmalonic acid (MMA) and homocysteine to assess for functional B12 deficiency despite high serum levels 4
• Celiac disease screening (tissue transglutaminase antibodies) as this commonly causes iron malabsorption with paradoxical lab findings 6
• Lead level given the cognitive symptoms and iron deficiency, which increases lead absorption 4, 7

Most Likely Diagnosis

This pattern is most consistent with iron-deficient erythropoiesis due to:

1. Malabsorption (celiac disease, inflammatory bowel disease) causing low iron availability despite adequate stores 1, 6
2. Chronic inflammation elevating ferritin while simultaneously impairing iron utilization for RBC production 1
3. Genetic disorders of iron metabolism such as iron-refractory iron deficiency anemia (IRIDA) due to TMPRSS6 mutations, where ferritin can be normal-to-elevated but iron saturation is severely low 1

Critical Clinical Pitfalls

Do not dismiss iron deficiency based on normal ferritin alone - transferrin saturation <20% is diagnostic of inadequate iron for erythropoiesis regardless of ferritin level 1, 6

The cognitive symptoms warrant urgent evaluation - iron deficiency causes developmental delays, decreased attention, and behavioral disturbances that may persist beyond school age if not corrected 7

Screen for celiac disease before initiating iron therapy - treating iron deficiency without addressing malabsorption will result in treatment failure 6

Management Algorithm

1. Confirm iron-deficient erythropoiesis with MCV, RDW, and erythrocyte protoporphyrin 1
2. Identify inflammation with CRP/ESR to explain ferritin-iron saturation discordance 1
3. Screen for malabsorption with celiac panel and consider GI evaluation 6
4. Assess functional B12 status with MMA and homocysteine given neurological symptoms 4
5. Initiate oral iron therapy (ferrous sulfate) if absorption is intact, or consider parenteral iron if malabsorption is confirmed 2, 6
6. Monitor response at 2-4 weeks with repeat hemoglobin and iron studies 2, 3

If oral iron fails after 3 months of adequate dosing, genetic testing for TMPRSS6 mutations should be considered 1.