Differential Diagnosis for Normal H&H with Low Transferrin and Low Serum Iron

• Single Most Likely Diagnosis

  • Anemia of Chronic Disease (ACD): This condition is characterized by low serum iron and low transferrin levels, despite normal hemoglobin and hematocrit (H&H) values. ACD is often seen in patients with chronic infections, inflammatory diseases, or malignancies, where the body's iron is sequestered, making it unavailable for erythropoiesis, and transferrin levels decrease as part of the acute phase response.

• Other Likely Diagnoses

  • Chronic Inflammation: Conditions such as rheumatoid arthritis, chronic infections, or other inflammatory diseases can lead to low serum iron and transferrin due to the body's inflammatory response, which can cause changes in iron metabolism and reduce transferrin production.
  • Nephrotic Syndrome: This condition involves significant proteinuria, including the loss of transferrin, leading to low serum transferrin levels. The low serum iron might be due to the body's attempt to conserve iron or due to the inflammatory component of the disease.
  • Malnutrition: Poor dietary intake of iron and proteins (including transferrin) can lead to low levels of these markers, even in the absence of anemia.

• Do Not Miss Diagnoses

  • Hemochromatosis: Although less likely given the low serum iron, some forms of hemochromatosis can present with low transferrin saturation due to the body's attempt to regulate iron overload. Missing this diagnosis could lead to significant morbidity due to iron accumulation in vital organs.
  • Thalassemia Major: While typically associated with low H&H, in some cases, especially with frequent transfusions, the H&H might be within the normal range. Low transferrin and iron could be seen due to transfusion-related iron overload and subsequent regulation of iron metabolism.

• Rare Diagnoses

  • Atransferrinemia: A rare genetic disorder characterized by the absence or very low levels of transferrin, leading to low serum iron levels despite adequate iron stores. This condition can result in tissue iron overload.
  • Aceruloplasminemia: Another rare genetic disorder that affects iron metabolism, leading to low serum iron and transferrin levels, and can cause neurological symptoms and retinal degeneration due to iron accumulation.