Dysmetabolic Hyperferritinemia: All Iron Overload Is Not Hemochromatosis

TLDR

Iron overload can arise from genetic or acquired disturbances, causing organ damage, with hereditary hemochromatosis being the most common genetic form, yet the clinical approach for patients with normal transferrin saturation remains unclear. The study proposes an approach for patients exhibiting hyperferritinemia with normal transferrin saturation. Screening involves measuring transferrin saturation and, if >45%, testing for hemochromatosis genes.

Abstract

Disturbances in iron metabolism can be genetic or acquired and accordingly manifest as primary or secondary iron overload state. Organ damage may result from iron overload and manifest clinically as cirrhosis, diabetes mellitus, arthritis, endocrine abnormalities and cardiomyopathy. Hemochromatosis inherited as an autosomal recessive disorder is the most common genetic iron overload disorder. Expert societies recommend screening of asymptomatic and symptomatic individuals with hemochromatosis by obtaining transferrin saturation (calculated as serum iron/total iron binding capacity × 100). Further testing for the hemochromatosis gene is recommended if transferrin saturation is >45% with or without hyperferritinemia. However, management of individuals with low or normal transferrin saturation is not clear. In patients with features of iron overload and high serum ferritin levels, low or normal transferrin saturation should alert the physician to other - primary as well as secondary - causes of iron overload besides hemochromatosis. We present here a possible approach to patients with hyperferritinemia but normal transferrin saturation.