Iron overload patients with unknown etiology from national survey in Japan

Abstract

Transfusion is believed to be the main cause of iron overload in Japan. A nationwide survey on post-transfusional iron overload subsequently led to the establishment of guidelines for iron chelation therapy in this country. To date, however, detailed clinical information on the entire iron overload population in Japan has not been fully investigated. In the present study, we obtained and studied detailed clinical information on the iron overload patient population in Japan. Of 1109 iron overload cases, 93.1% were considered to have occurred post-transfusion. There were, however, 76 cases of iron overload of unknown origin, which suggest that many clinicians in Japan may encounter some difficulty in correctly diagnosing and treating iron overload. Further clinical data were obtained for 32 cases of iron overload of unknown origin; median of serum ferritin was 1860.5 ng/mL. As occurs in post-transfusional iron overload, liver dysfunction was found to be as high as 95.7% when serum ferritin levels exceeded 1000 ng/mL in these patients. Gene mutation analysis of the iron metabolism-related genes in 27 cases of iron overload with unknown etiology revealed mutations in the gene coding hemojuvelin, transferrin receptor 2, and ferroportin; this indicates that although rare, hereditary hemochromatosis does occur in Japan.

HFE-Related Hemochromatosis in a Chinese Patient: The First Reported Case

“…It is well known that HFE p.C282Y is very common and responsible for most cases of hemochromatosis in Caucasians (Kowdley et al, 2019). However, HFE p.C282Y has been rarely identified in East Asians in previous studies (Choi et al, 2002;Lin et al, 2007;Ikuta et al, 2017). Furthermore, HFE p.C282Y mutation had been identified neither in a variety of disorders in China such as chronic hepatitis C, nonalcoholic fatty liver disease (Lin et al, 2005), cardiovascular disease (Bi et al, 2013), myelodysplastic syndromes, and aplastic anemia (Nie et al, 2010), nor in general population (Lin et al, 2007).…”

Non-HFE mutations in haemochromatosis in China: combination of heterozygous mutations involving HJV signal peptide variants

“…HJV homozygous mutation p.D249H and p.Q312X were identified in two cases from Japan,12–14 while a p.I287S was identified in a Chinese case 15 . HJV heterozygote mutation p.D249H, p.Q312X and A75V were also identified in a Japanese case,16 while a compound heterozygote for HJV p.Q6H/C321X and I281T was also identified in a Chinese case 17. However, one case harboured only heterozygote HJV p.Q6H/C321X, and it was proposed that previously unrecognised environmental or other genetic factors may have interacted with the heterozygous genotype in the patient 18.…”

The mechanisms of systemic iron homeostasis and etiology, diagnosis, and treatment of hereditary hemochromatosis

“…The same mutation was found in the Huh-7 hepatoma cell line and was shown to prevent the translocation of HFE to the cell surface [88]. In addition, families with various types of HH were sporadically reported from Asian countries, including Japan, China, and Pakistan [67,87,[89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104]. In Japan, mutations in HFE2 (type 2A), TFR2 (type 3), and SLC40A1 (type 4) seem relatively common causes of HH [97].…”