What is the appropriate initial management for iron deficiency in a 17‑year‑old female with autism who has low ferritin but normal serum iron, TIBC, and transferrin saturation?

Management of Iron Deficiency in a 17-Year-Old Female with Autism

This patient has iron deficiency without anemia and should be treated with oral iron supplementation at 100–200 mg elemental iron daily in divided doses, with follow-up laboratory assessment at 8–10 weeks. 1

Laboratory Interpretation

Your patient's iron studies reveal absolute iron deficiency based on the following pattern:

• Ferritin 18 ng/mL is below the diagnostic threshold of <30 ng/mL for absolute iron deficiency in patients without inflammation 2, 3
• Transferrin saturation 29% is actually normal (>20%), which initially seems contradictory 3
• Elevated transferrin 97 mg/dL and elevated TIBC 398 mg/dL represent the body's compensatory response to depleted iron stores, producing more transferrin to maximize iron-binding capacity 1
• Normal serum iron 115 mcg/dL does not exclude iron deficiency because serum iron has high intra-individual variability with diurnal fluctuations and post-prandial changes 3

The combination of low ferritin (<30 ng/mL) with elevated TIBC is the classic laboratory signature of iron deficiency, indicating a high proportion of vacant iron-binding sites on transferrin despite seemingly "normal" serum iron and transferrin saturation. 1 The ferritin level is the most specific indicator of depleted iron stores and should guide your diagnosis. 2

Autism-Specific Considerations

Iron deficiency is clinically relevant in autism spectrum disorder:

• Elevated serum transferrin levels (which reflect low iron stores) are associated with increased risk of autism in Mendelian randomization studies, suggesting iron deficiency may play a role in autism pathophysiology 4
• However, U.S. data show that only 8% of children with autism have low ferritin (<12 µg/L), which is not substantially higher than the general pediatric population 5
• Iron deficiency in psychiatric populations (including autism) can worsen hyperemotivity, anxiety, irritability, aggressiveness, sleep disorders, cognitive performance, and restless-leg syndrome 6
• Oral iron treatment in iron-deficient psychiatric patients has shown regression/remission of symptoms in responsive patients, particularly through its role in monoaminergic neurotransmitter synthesis 6

Common pitfall: Children with autism often have food selectivity and restricted diets, putting them at ongoing risk for recurrent iron deficiency even after initial repletion. 5

Treatment Algorithm

Step 1: Confirm No Inflammation

• Measure C-reactive protein to exclude chronic inflammation that could falsely elevate ferritin 3
• If CRP is elevated, the ferritin threshold for iron deficiency rises to <100 ng/mL 3
• In this case, ferritin 18 ng/mL confirms deficiency regardless of inflammatory status 3

Step 2: Initiate Oral Iron Supplementation

• Prescribe 100–200 mg elemental iron daily in divided doses (e.g., ferrous sulfate 325 mg twice daily provides ~130 mg elemental iron/day) 1
• Alternate-day dosing may provide better absorption with fewer gastrointestinal adverse effects compared to daily dosing 1
• Common adverse effects include constipation, diarrhea, and nausea 1
• Take iron on an empty stomach (1 hour before or 2 hours after meals) to maximize absorption, or with food if gastrointestinal symptoms occur

Step 3: Address Underlying Causes

• Evaluate menstrual blood loss patterns in this adolescent female, as menstruation is the most common cause of iron deficiency in this population 3
• Assess dietary iron intake using a 3-day food record, focusing on heme iron sources (meat, poultry, fish) and non-heme sources (fortified cereals, legumes, leafy greens) 5
• Screen for malabsorption (celiac disease, inflammatory bowel disease) if dietary intake appears adequate 3
• Review medications for NSAIDs or other drugs that may cause occult gastrointestinal blood loss 3

Step 4: Monitor Response

• Repeat iron studies (ferritin, TIBC, transferrin saturation) at 8–10 weeks after initiating oral iron 1
• Target ferritin ≥30–45 ng/mL and transferrin saturation ≥20% to ensure adequate iron stores for erythropoiesis 3
• Expected hemoglobin rise of 1–2 g/dL within 4–8 weeks if anemia develops 3

Step 5: Consider Intravenous Iron if Oral Therapy Fails

Indications for switching to IV iron: 1

• Gastrointestinal intolerance to oral iron (nausea, constipation)
• Lack of hematologic response after 8–10 weeks of adequate oral therapy
• Documented malabsorption
• Patient non-adherence to oral regimen

IV iron formulations (ferric carboxymaltose, iron sucrose, low-molecular-weight iron dextran) bypass intestinal absorption and directly replenish iron stores. 3, 1 If IV iron is used, do not recheck iron studies within 4 weeks of infusion because circulating iron interferes with assay accuracy; wait 4–8 weeks after the last dose. 3, 1

Critical Pitfalls to Avoid

• Do not rely on serum iron or transferrin saturation alone to exclude iron deficiency; ferritin is the most specific indicator of depleted iron stores 2, 7
• Do not supplement iron when ferritin is normal or high (>100 ng/mL without inflammation), as this is potentially harmful 1
• Do not measure iron parameters too early (<8 weeks for oral iron, <4 weeks for IV iron), as this yields unreliable results 3, 1
• Do not ignore dietary counseling in patients with autism who have restricted diets, as ongoing nutritional deficiency will lead to recurrent iron depletion 5
• Do not overlook the potential for symptom improvement in autism-related behavioral symptoms (anxiety, irritability, sleep disturbance) with iron repletion, as iron plays a role in neurotransmitter synthesis 6