Differential Diagnosis for High Serum Iron Level but Low Ferritin

• Single most likely diagnosis

  • Hemolysis: This condition involves the breakdown of red blood cells, which can lead to an increase in serum iron levels due to the release of iron from the lysed cells. However, ferritin levels may remain low because ferritin reflects iron storage, and in hemolysis, the body's iron stores may not be adequately replenished or may be depleted due to chronic hemolysis and subsequent increased iron excretion or utilization.

• Other Likely diagnoses

  • Acute iron overdose: Ingestion of a large amount of iron can lead to high serum iron levels. Ferritin, being an acute phase reactant, might not have had time to increase in response to the acute rise in serum iron, or its levels could be low if the body's iron stores were previously depleted.
  • Ineffective erythropoiesis (e.g., in myelodysplastic syndromes): In these conditions, the bone marrow produces red blood cells inefficiently, leading to increased iron turnover and potentially high serum iron levels. Despite this, ferritin levels might be low due to the underlying disorder affecting iron utilization and storage.
  • Chronic liver disease: Liver dysfunction can disrupt the normal regulation of iron metabolism, potentially leading to elevated serum iron levels. However, ferritin levels, which are also an acute phase reactant, might be low in certain liver conditions where there's a lack of inflammation or where the liver's ability to produce ferritin is impaired.

• Do Not Miss diagnoses

  • Hemochromatosis with recent bleeding: Although hemochromatosis typically presents with high ferritin levels due to iron overload, a recent significant bleed could temporarily lower ferritin levels while serum iron remains elevated due to the release of iron from hemolysis or the bleed itself.
  • Sideroblastic anemia: A group of disorders characterized by the accumulation of iron in the mitochondria of red blood cell precursors. This can lead to increased serum iron levels, but ferritin might be low, especially if the condition is not associated with significant inflammation or if there's a component of iron deficiency.

• Rare diagnoses

  • Atransferrinemia: A rare genetic disorder characterized by the absence or very low levels of transferrin, the protein responsible for transporting iron in the blood. This leads to high serum iron levels because iron is not properly bound and transported, but ferritin levels can be low due to the body's inability to effectively utilize and store iron.
  • Aceruloplasminemia: Another rare genetic disorder involving a deficiency of ceruloplasmin, a protein necessary for the oxidation of ferrous iron to ferric iron, which is then bound by transferrin. This condition can result in elevated serum iron levels and low ferritin due to impaired iron metabolism and storage.