H63D Syndrome Type-1: What you should know about it (2023)

In most practices, clinics and professional societies, a homozygous H63D gene mutation was and is generally considered relatively harmless, since carriers of this mutation very rarely develop classic ferritin-related hemochromatosis. Ferritin levels are usually normal or even rather low in these patients, so everything seems fine. Due to the fragmentation of medicine into many specialties, on a meta-level, hardly anyone has noticed that people with a homozygous H63D mutation can develop a very severe disease, H63D Syndrome. The key to understanding the phenotype is non- transferrin-bound iron, or NTBI. H63D Syndrome is a separate phenotype (clinical picture) of a homozygous mutation of the HFE gene H63D, which is otherwise known to cause at best a mild classical hemochromatosis. H63D syndrome, however, is not just another type of hemochromatosis, it is a serious syndrome caused by non- transferrin bound iron (NTBI) which is the result of an elevated transferrin saturation (50-100%) due to hypotransferrinemia which is the consequence of a homozygous mutation of HFE gene H63D.