Three loss-of-function mutations in the hemochromatosis gene (HFE), namely, C282Y (c.845G>A), H63D (c.187C>G), and S65C (c.193A>T), account for the vast majority of HH cases.
However, because of the rarity and difficulty in making the genetic diagnosis, a large proportion of patients with non-HFEHH might have been undiagnosed; therefore, awareness of this disorder is important.
Although the relationship between hereditary hemochromatosis and mutations in the HFE gene was discovered more than 20 years ago, information on the in vivo regulation of HFE protein expression is still limited.
- Our "one-button" order that restricts HFE genetic tests to patients with transferrin saturation greater than 45% is consistent with published practice guidelines and detected 100% of new patients with HFE-related hereditary hemochromatosis.
All clinical outcomes analyzed were more prevalent in the juvenile forms of HH, with the exception of arthritis and arthropathy, which were more commonly seen in HFEHH.
Mutations in the <i>HFE</i> (hemochromatosis) gene cause hereditary hemochromatosis, an iron overload disorder that is hallmarked by excessive accumulation of iron in parenchymal organs.
The population also contain individuals with the Swedish long QT syndrome (LQTS1) founder mutation (<i>KCNQ1</i>/p.Y111C) which in homozygotes causes the Jervell & Lange Nielsen syndrome (JLNS) and hearing loss (HL).Aims of the study were to test whether the Swedish long QT founder mutation originated in an ancestral HFE family and if carriers had an increased risk for hemochromatosis (HH), a treatable disorder.
The HFE molecule controls iron uptake from gut, and defects in the molecule have been associated with iron overload, particularly in hereditary hemochromatosis.
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis.
In patients with a combination of elevated TSAT and ferritin in the absence of anaemia, and after exclusion of HFE-related HH, rare forms of HH should be considered.