What is the most likely diagnosis and initial work‑up for a young premenopausal woman with persistent low hemoglobin, 1–2 yearly episodes of diffuse body pain, chronic ear fullness, and fatigue after mild exercise, whose menopausal mother also has low hemoglobin?

Most Likely Diagnosis: Iron Deficiency Anemia

The most likely diagnosis is iron deficiency anemia (IDA) secondary to menstrual blood loss, given the patient's young age, female sex, low hemoglobin, maternal history of anemia, and constellation of symptoms including fatigue and diffuse body pain. 1, 2, 3

Initial Diagnostic Work-Up

Essential First-Line Laboratory Tests

• Complete blood count (CBC) with red cell indices (hemoglobin, hematocrit, MCV, MCH, MCHC, RDW) using an automated analyzer to characterize the anemia pattern 4
• Serum ferritin (diagnostic threshold <30 μg/L confirms IDA in premenopausal women) 1, 2
• Transferrin saturation (TSAT <20% supports iron deficiency) 1, 2, 3
• Reticulocyte count to assess bone marrow response 4
• Peripheral blood smear to evaluate red cell morphology 4

Interpretation of Iron Studies

• A low or normal MCV (<100 fL), low serum ferritin (<30 μg/L), and/or low transferrin saturation (<20%) is sufficient to confirm IDA in young women 2
• High RDW with normal or low MCV suggests possible iron deficiency 1
• Hemoglobin <12 g/dL in nonpregnant women defines anemia 2

Clinical Context Supporting IDA Diagnosis

Risk Factors Present

• Premenopausal status with menstrual losses is the leading cause of IDA in young women, with prevalence of 5–12% in otherwise healthy premenopausal women 1
• Maternal history of low hemoglobin suggests possible familial pattern of iron deficiency or menorrhagia 1
• Early exhaustion after physical exercise is consistent with reduced oxygen-carrying capacity from anemia 5, 2
• Diffuse body pain episodes may reflect tissue hypoxia or associated symptoms of severe anemia 5, 6

When to Screen for Celiac Disease

• All premenopausal women with IDA should be considered for serological screening for celiac disease, as CD is found in up to 4% of cases 1

Differential Diagnoses to Consider

Less Likely but Important Alternatives

• Hereditary methemoglobinemia (Type I) can present with cyanosis, fatigue, and headache, but typically shows MetHb levels >10% and characteristic slate-gray appearance from birth 1, 7
• Pernicious anemia presents with megaloblastic anemia (elevated MCV), neurologic symptoms (paresthesias, ataxia, weakness), and is less common in young women 8
• Thalassemia minor should be considered if anemia is unresponsive to iron therapy, particularly in women of African, Mediterranean, or Southeast Asian ancestry 1

Red Flags Requiring Further Investigation

Endoscopic investigation is NOT routinely indicated in young menstruating women with IDA unless specific red flags are present: 1

• Age over 50 years
• Non-menstruating status (e.g., post-hysterectomy)
• Associated alarm symptoms (unexplained weight loss, GI bleeding, dysphagia)
• Family history of colorectal cancer (two first-degree relatives or one before age 50)
• Recurrent or persistent IDA disproportionate to menstrual losses
• Positive celiac serology requiring endoscopic confirmation

Initial Management Approach

Iron Replacement Therapy

• Prescribe oral iron supplementation at 60–120 mg/day of elemental iron for treatment of confirmed IDA 1
• Counsel the patient about dietary sources of iron and foods that enhance iron absorption 1
• A 4-week trial of oral iron therapy can serve as both diagnostic and therapeutic intervention 2

Follow-Up Protocol

• Repeat hemoglobin measurement after 4 weeks of iron therapy to confirm response 1, 2
• Expected response: hemoglobin should increase by approximately 1–2 g/dL after 3–4 weeks of adequate iron supplementation 3
• If anemia does not respond to iron treatment after 4 weeks despite compliance, further evaluate with additional laboratory tests including vitamin B12, folate, and renal function 1, 2
• Continue iron treatment for 2–3 months after hemoglobin normalizes to replenish iron stores 1

Addressing Associated Symptoms

• Ear fullness may be unrelated to anemia or could reflect Eustachian tube dysfunction; consider ENT evaluation if persistent
• Diffuse body pain episodes should improve with correction of anemia; if persistent, consider alternative diagnoses (fibromyalgia, autoimmune conditions)
• Exercise intolerance typically resolves as hemoglobin levels normalize with iron repletion 5, 2

Common Pitfalls to Avoid

• Do not perform extensive GI investigation in young menstruating women without additional red flag symptoms, as underlying GI pathology is extremely uncommon in this population 1
• Do not overlook celiac disease screening, as it is found in up to 4% of IDA cases and requires specific treatment 1
• Do not assume anemia is normal or acceptable in young women; it always warrants investigation and treatment 2, 3
• Do not use MCV alone to screen for iron deficiency in the presence of other conditions; serum ferritin and transferrin saturation are more reliable 4, 2