Iranian hereditary hemochromatosis patients: Baseline characteristics, laboratory data and gene mutations

Abstract

SummaryBackgroundHereditary hemochromatosis (HH) is the most common autosomal recessive disorder in white people, characterized by highly abnormal uptake of iron from the gastrointestinal tracts. Recently, mutation studies have focused to detect the genes responsible for HH.Material/MethodsIn this cross-sectional study, 12 HH patients were recruited, who were referred to Firoozgar Hospital, Tehran, Iran. In addition to the clinical assessments, a complete laboratory evaluation, imaging modalities, histopathologic assessment, atomic absorption spectrophotometry and gene mutation study were performed. The genetic study for HFE gene mutation was examined for all of the patients since 2006, while non-HFE mutation was conducted since December 2010 (only for 1 of them).ResultsTwelve patients were evaluated consisting of 11 men and 1 woman, with the mean age of 39.58±12.68 yr. The average of atomic iron loads was 13.25±4.83-fold higher than normal standards. Four patients had heterozygotic mutation of H63D (33.3%). There was no significant difference in either the iron load of liver (P=0.927) and heart (P=0.164) or serum concentration of ferritin (P=0.907) and TIBC (P=0.937) between the HFE-mutant and without HFE mutation HH cases.ConclusionsIn contrast to other studies, C282Y mutation was not detected in any of our Iranian HH patients. Heterozygotic mutations of H63D (HFE) and TFR2 (non-HFE) genes were found to be more common in these patients. Similar to previous reports, these mutations were not found to be significantly associated with severity of presentation in HH patients.

Iron storage disease in Asia‐Pacific populations: The importance of non‐HFE mutations

“…). The AVAQ621‐624del mutation, which was originally reported in Italy, has also been found in Japanese patients with HH and more recently in a patient from Iran …”

“…The AVAQ621-624del mutation, which was originally reported in Italy, has also been found in Japanese patients with HH 50 and more recently in a patient from Iran. 51 Other mutations that have been reported as the cause of type 3 HH in Asia are L490R and P555fsX561, both in Japanese patients 52 and R481H in a Taiwanese patient. 53 The R481H mutation was reported in a female with severe iron overload, but only in the heterozygous state; whether an additional mutation or other factors contributed to her iron overload are not clear.…”

Recent advances in hemochromatosis: a 2015 update

“…Types I-III are linked to altered or reduced expression of hepcidin [11,25,27], whereas type IV results from reduced iron export [1,28]. Mutations in HFE, HJV, HAMP, TFR2 and SLC40A1 have been linked to the various types of hemochromatosis [11,25,29], each displaying different onsets, severities and prevalences [2,4,9,25,27,[29][30][31][32][33] (Table 1).…”

“…Type III hemochromatosis is a mutation of TFR2 [1,2,25,29,30,41]. Whilst the function of TFR2 is not completely understood, it is believed to bind to sense transferrin in hepatocytes by binding to HFE [40].…”

“…It is among the most common autosomal recessive conditions of Caucasian populations [1,2]. Resulting from abnormal regulation of iron absorption, excess dietary intake leads to increased body iron stores.…”