What is the cause of anemia in a 17-month-old child that is refractory to iron supplementation with normal iron studies, indicating a possible diagnosis of anemia of chronic disease or other underlying condition?

From the Guidelines

In a 17-month-old child with anemia refractory to iron supplementation and normal iron studies, anemia of chronic disease or other underlying conditions such as inherited disorders of iron metabolism or heme synthesis should be considered as potential causes [ 1 ].

Key Considerations

• The child's anemia may be due to chronic inflammation, which can lead to an increase in serum ferritin levels, making it difficult to diagnose iron deficiency [ 1 ].
• Vitamin B12 or folate deficiency should also be considered as potential causes of anemia, and a trial of supplementation may be warranted [ 1 ].
• Evaluation for other causes of anemia, including lead poisoning or inherited disorders, should be undertaken, and consultation with a pediatric hematologist may be necessary to guide further management.

Diagnostic Approach

• Measurement of inflammatory parameters such as ESR or CRP can help aid in the diagnosis of anemia of chronic disease [ 1 ].
• Transferrin saturation and serum ferritin levels should be assessed to determine the presence of iron deficiency or anemia of chronic disease [ 1 ].
• Genetic testing may be necessary to diagnose inherited disorders of iron metabolism or heme synthesis [ 1 ].

From the Research

Possible Causes of Anemia

• Anemia in a 17-month-old child that is refractory to iron supplementation with normal iron studies may be caused by a genetic condition, such as iron-refractory iron deficiency anaemia (IRIDA), which is characterized by mutations in the TMPRSS6 gene 2.
• Other possible causes of anemia in this age group include pulmonary diseases, which can lead to nontraumatic pulmonary bleeding, resulting in anemia and pulmonary hemosiderosis 3.
• Although less likely in this scenario, given the normal iron studies, diet-related iron deficiency anaemia is also a possible cause of anemia in children of this age group, particularly if the child has a poor diet 4.

Underlying Conditions

• IRIDA is a rare cause of iron deficiency anaemia that is characterized by a poor response to oral iron treatment, and is caused by mutations in the TMPRSS6 gene 2.
• Pulmonary diseases, such as those that cause nontraumatic pulmonary bleeding, can also lead to anemia and may be associated with other symptoms, such as respiratory distress 3.
• Other underlying conditions, such as chronic diseases or immune system disorders, may also contribute to the development of anemia in children, although these are not directly supported by the provided evidence.

Diagnostic Considerations

• A diagnosis of IRIDA or other genetic causes of iron deficiency anaemia may be considered in children who do not respond to oral iron treatment, and who have normal iron studies 2.
• A thorough diagnostic workup, including allergy/immunology consultation, may be necessary to determine the underlying cause of anemia in children with complex or unclear presentations 3.