HFE gene mutation, C282Y causing hereditary hemochromatosis in Caucasian is extremely rare in Korean population

Hereditary hemochromatosis (HFE), which affects 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals in Western population, results in multiple organ damage caused by iron deposition, and is treatable if detected early. C282Y mutation in HFE gene has been known to be responsible for the most hereditary hemochromatosis cases and 5-10% of white subjects are heterozygous for this mutation. However, the prevalence of hemochromatosis in the Asian population was reported to be very low and ethnic heterogeneity has been suspected. The aim of our study was to determine the prevalence of heterozygosity and homozygosity for the C282Y HFE gene mutations in 502 unrelated Koreans. Results revealed that none of them had the mutant gene, suggesting a significant ethnic difference when compared with Caucasians. Our study excluded underlying possibility of hereditary hemochromatosis in Korean which could mimic the findings of alcoholic liver disease with iron overload or liver cirrhosis with chronic hepatitis C.

Idiopathic hemochromatosis: a study in a large Puerto Rican family

We studied 13 first-degree relatives in a large family with an index case of idiopathic hemochromatosis to detect the relatives with evidence of iron overloading. Serum iron, total iron binding capacity (TIBC), and serum ferritin levels were measured in all family members. We also performed HLA typing to identify the relatives who are homozygous with the proband and genetically predisposed to develop the disease. The family was composed of the parents and 12 siblings including the index case. The mean age of the siblings was 25 years. None presented with evidence of iron overload by the iron biochemical tests. HLA typing demonstrated six homozygous siblings with the proband. In separate analysis these siblings did not present abnormalities in any of the iron biochemical tests. These homozygous relatives were followed for one year after initial evaluation and none presented abnormalities in the iron studies during this period. These results are contradictory to other previous studies done in families with idiopathic hemochromatosis. The most feasible explanations for these findings are the young age of these siblings and the predominance of females among them. We consider that these homozygous relatives must be followed for their life-times with iron studies to detect a possible increase in iron stores as expected in later ages