Iron Storage Disorders

Abstract

IRON OVERLOAD DISORDERS Hereditary Hemochromatosis (OMIM 235200) Iron overload states can be classified as primary or secondary. There are many disorders that can lead to iron overload (Table 27.1). This chapter focuses on hereditary hemochromatosis (HHC), juvenile hemochromatosis (JHC), and secondary iron overload (primarily transfusion associated) in the pediatric patient and on neonatal hemochromatosis. For a discussion of the rarer entities, the reader is referred to several recent reviews [1, 2]. Physiology and Pathophysiology of Iron Overload Iron is one of the more tightly regulated nutrients in the body. Humans have no significant excretory pathway for iron. Thus, body iron stores are normally controlled at the level of absorption, matching absorption to physiologic requirements. Under normal circumstances, only about 1 mg of elemental iron is absorbed per day (Figure 27.1), in balance with gastrointestinal losses. Intestinal iron absorption is increased by low body iron stores (storage regulation) [3], increased erythropoiesis (erythropoietic regulation) [3], anemias associated with ineffective erythropoiesis (thalassemias, congenital dyserythropoietic anemias, and sideroblastic anemia), and acute hypoxia. Both dietary iron intake (dietary regulation) and systemic inflammation can temporarily decrease iron absorption and availability, even in the presence of iron deficiency [4–6]. Duodenal crypt cells sense body iron status and are programmed for iron absorption as they mature. Duodenal and proximal jejunal enterocytes are responsible for iron absorption. Low gastric pH helps dissolve iron, which is then enzymatically reduced to the ferrous form by ferrireductase [7].