Differential Diagnosis for Low Serum Iron with Normal UIC and Transferrin Saturation

• Single Most Likely Diagnosis
  • Chronic Disease: In chronic diseases such as chronic infections, inflammation, or malignancies, serum iron can be low due to the body's acute phase response, which increases hepcidin levels, leading to decreased iron absorption and increased iron sequestration in macrophages. Despite low serum iron, the body's iron stores (as reflected by UIC) and transferrin saturation might remain normal because the iron is not being utilized effectively due to the inflammatory state.
• Other Likely Diagnoses
  • Early Iron Deficiency: Before iron deficiency anemia becomes overt, with decreased iron stores but not yet to the point where UIC and transferrin saturation are significantly affected. This stage might present with low serum iron but still within the normal range for UIC and transferrin saturation.
  • Hypothyroidism: Can lead to decreased iron absorption and utilization, potentially resulting in low serum iron levels even when UIC and transferrin saturation are normal.
• Do Not Miss Diagnoses
  • Thalassemia Minor: Although typically associated with microcytic anemia, in some cases, especially if the patient has a mild form or is a carrier, the serum iron might be low due to ineffective erythropoiesis, but UIC and transferrin saturation could remain normal due to the body's compensatory mechanisms.
  • Chronic Kidney Disease (CKD): CKD can lead to a complex picture of iron metabolism, including low serum iron due to inflammation and hepcidin dysregulation, despite potentially normal UIC and transferrin saturation, especially in early stages.
• Rare Diagnoses
  • Atransferrinemia: A rare genetic disorder characterized by the absence or very low levels of transferrin, leading to low serum iron but potentially normal UIC and transferrin saturation measurements due to the lack of transferrin to bind and transport iron.
  • ** Aceruloplasminemia**: A rare genetic disorder affecting iron metabolism, characterized by the absence of ceruloplasmin, leading to iron accumulation in tissues but potentially low serum iron levels, with UIC and transferrin saturation being normal or not reflective of the underlying pathology.