Concordance of iron storage in siblings with genetic hemochromatosis: evidence for a predominantly genetic effect on iron storage.

Phenotypic concordance between siblings has been demonstrated in some inherited conditions, and such data provide strong evidence that the severity of disease is affected by genetic factors. We assessed the concordance of liver iron stores between siblings in 22 sibling pairs (15 same-sex pairs and 7 opposite-sex pairs) with genetic hemochromatosis. In this study population a wide range was found in the hepatic iron concentration and the hepatic iron index (32 to 833 mumol/gm dry wt and 1.65 to 14.4, respectively), which could not be accounted for by differing exposure to the environmental factors that influence iron stores. Despite the large variation of hepatic iron concentration within the group, siblings of identical sex had accumulated similar amounts of liver iron. A highly significant correlation for hepatic iron concentration (r = 0.81) and hepatic iron index (r = 0.70) was found between siblings of the same sex. The hepatic iron concentration and the hepatic iron index of one sibling was less than 50% of the other in only three same-sex sibling pairs. In each instance, reasons existed (blood donation, age at diagnosis and human leukocyte antigen nonidentity) for this discordance. In six of the seven opposite-sex pairs, the woman had lower hepatic iron stores than her male sibling, consistent with previous studies on the extent of iron overload in women and its modification by physiological blood loss.(ABSTRACT TRUNCATED AT 250 WORDS)