Retrospective Review of Patients of Southeast Asian Descent with Persistent Hyperferritinemia Who Are Negative for Hereditary Hemochromatosis.

Background and Methods. Isolated hyperferritinemia is a common clinical finding. However, known HFE mutations C282Y and H63D have not been well-described in the Asian population. As well, evaluation of hyperferritinemia in the Asian population is confounded by chronic hepatitis B infection. We performed a retrospective case review of 79 patients of Southeast Asian ethnicity referred to three subspecialists in a tertiary care teaching hospital from January 1997 until July 2006 for assessment of hyperferritinemia. A subset of patients may represent a novel syndrome of isolated hereditary hyperferritinemia.

Results. 35 patients had identifiable secondary causes for their hyperferritinemia. 4 had clinical or biopsy proven iron overload consistent with hemochromatosis. 40 had isolated hyperferritinemia. Of the 35 patients with secondary causes, 26 had liver disease; 16 with viral hepatitis. Other causes included hematologic disorders (10), malignancy (2) and inflammatory arthritis (2). On liver biopsy, 8 patients showed no increase in stainable iron while 10 showed mild-moderate increase. 7 patients were negative for C282Y and H63D mutations. Of the 40 cases of isolated hyperferritinemia, 38 had normal liver enzymes. 2 had liver biopsies showing mild increase in stainable iron. 9 patients underwent C282Y and H63D genotyping with 1 patient being H63D heterozygous. 8 index patients had first-degree relatives with hyperferritinemia. 3 families were identified with more than 2 members affected, suggestive of a possible hereditary hyperferritinemia syndrome.

Conclusion. Hyperferritinemia appears to be relatively common in Asians but classic hemochromatosis is not. Liver disease is a frequent cause of hyperferritinemia in the Asian population. We have, however, discovered a small group of healthy patients with no evidence of liver disease and isolated hyperferritinemia that in some cases appears to be familial. This has not been previously reported.