Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred

Abstract

Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.