Inherited Iron Overload

Abstract

Halliday, J. W. (The Liver Group, Department of Medicine, University of Queensland, Royal Brisbane Hospital, Brisbane, Australia). Inherited iron overload. Several inherited forms of iron overload have been described. It is now accepted that HC, usually regarded as a disease of adult life, is an inherited disorder, hence all first degree relatives must be presumed to be at increased risk of developing iron overload and the diagnosis is now frequently made in young relatives. The combination of serum iron, transferrin saturation and serum ferritin determination will detect iron overload in an early, precirrhotic stage. Liver biopsy and the determination of hepatic iron concentration provide the definitive proof. Where HC is recognized sufficiently early to permit adequate removal of iron before cirrhosis has developed, the prognosis is excellent. Thus haemochromatosis as a clinical disease should be preventable in a large proportion of patients. Severe iron overload has been described in juveniles and also in neonates. These conditions are familial but whether they are HLA‐related has not been determined. Cardiac and endocrine disorders are frequently the presenting manifestations of parenchymal iron overload in the young and, at least in neonates, the condition is usually fatal in early infancy. It is not possible at present, to say whether these rare juvenile and neonatal forms of haemochromatosis are related to the much more common adult form. Identification of the gene for HC may assist in answering this question.

HLA Antigens and Serum Ferritin in Hemodialysis Patients

“…Iron overload is rare in patients treated with oral iron as long as the mechanisms regulat ing absorption of iron are preserved [5,36,41,43], On the other hand, although a correlation between SF levels and oral-iron dosage has been reported [39], the replenish ment of iron stores may require a long period in cases of previous iron deficiency as in our study [27,36,40].…”

“…These regulatory mechanisms of intestinal iron absorption are impaired in idiopathic hemochromatosis [5], although the precise defect has not yet been identified. Nevertheless, all possible causes (de fects in the systems of iron absorption, transport, storage or utilization) should be investigated in uremics classi-Tied according to their HLA type, in order to identify the pathophysiological nature of the problem.…”

“…Iron overload induced by parenteral iron in uremic patients is accompanied by a substantial reduction of intestinal iron absorption [5,21,42,43], This physiological mechanism may be altered in HLA A3, B7 or BI4 HD patients, producing an inappropriately high iron absorp tion unrelated to their stores, and explaining higher SF levels in these patients. These regulatory mechanisms of intestinal iron absorption are impaired in idiopathic hemochromatosis [5], although the precise defect has not yet been identified.…”

“…These antigens, specially A3, have been often found associated with idiopathic hemochromatosis [5][6][7][8]. Elevated serum ferritin (SF) and high tissue iron content have also been detected in H D patients carrying these antigens [9][10][11][12][13][14], These findings have not been obtained consistently [15], however, and several aspects of the problem have not yet been analyzed.…”

Management of Hemosiderosis Complicated by Coexistent Anemia with Recombinant Human Erythropoietin and Phlebotomy

“…Biopsy of the liver demonstrated marked iron deposition predominantly in the hepatocytes. A diagnosis of idiopathic hemochromatosis (IHC) was made on the basis of the pat tern of hepatic iron staining, elevated serum ferritin and percent sat uration of total iron-binding capacity, a family history of IHC, and se quelae of IHC-induced end-organ damage [3,4], Treatment was initi ated with intermittent phlebotomies. He transferred his care to our facility in July 1990, at which time the laboratory data revealed a white cell count of 5.1 x 109/1, a hemoglobin of 13.2 g/dl, a hematocrit of 37.7%, a platelet count of 130 x 109/1, a serum iron of 192 pg/dl (normal 40-175 pg/dl), serum iron-binding capacity of 216 pg/dl (normal 240-420 pg/dl), a transferrin saturation of 89% (normal 25-55%), a serum ferritin of 1,808.…”