1. Schuyler Tong, MD* 2. Elliott Vichinsky, MD*,† 1. *Department of Pediatrics and Pediatric Hematology Oncology, University of California at San Francisco Benioff Children’s Hospital Oakland, Oakland, CA 2. †Pediatric Hematology Oncology, University of California, San Francisco, CA Clinicians should recognize iron deficiency as a unique disease entity and understand the interconnection between iron deficiency and other systemic diseases. After completing this article, readers should be able to: 1. Recognize that iron deficiency is a separate entity that precedes iron deficiency anemia and in and of itself causes serious morbidity. 2. Identify iron deficiency as an associated sign for multiple underlying diseases, including inflammatory bowel disease and hereditary hemorrhagic telangiectasia. 3. Discuss the vulnerability of the brain to iron depletion. 4. Describe options for replenishing iron stores and the improvements in parenteral formulations of iron. Iron plays a role in multiple essential physiological functions, including oxygen transport, gene regulation, DNA synthesis, DNA repair, and brain function. Depletion of and inability to use iron disrupts these pathways and causes multiple morbidities. Iron deficiency anemia (IDA) is a well-known sequela, but iron deficiency alone, before the manifestation of microcytosis and anemia, may have negative implications for the health of pediatric patients. Of children 0 to 4 years of age, 20.1% have IDA in industrialized countries and the same is true of 39% of children in nonindustrialized countries. (1) Iron deficiency, independent of anemia, affects 2.3 billion people worldwide, including 50% of younger children and female teenagers. The recognition that iron deficiency puts children at risk for a myriad of poor outcomes is an important step in delivering effective health-care. Iron is absorbed from the diet in primarily the duodenum and the jejunum. The body has been known to regulate the amount of absorption; it has been estimated that a diet with 10 to 20 mg of iron leads to approximately 1 mg of iron …