Hereditary hemochromatosis is reflected in the iron isotope composition of blood

Abstract

It has recently been shown that the iron isotopic composition of blood differs between individuals and sexes, which is supposed to reflect individual differences in iron metabolism. We hypothesized that patients suffering from hereditary hemochromatosis would demonstrate alterations in the iron isotopic composition of blood due to persistent up-regulation of intestinal iron absorption. Blood from 30 patients with homozygous C282Y hemochromatosis was analyzed for iron isotopic composition by a newly developed technique using multicollector inductively coupled plasma mass spectrometry (MC-ICP-MS). Blood of patients with hemochromatosis is characterized by a higher 56 Fe/ 54 Fe isotope ratio than blood of healthy individuals, which are either members of an age-matched control group (n ‫؍‬ 10; P < .001) or young adults (n ‫؍‬ 36; P < .001). In patients with hereditary hemochromatosis, the 56 Fe/ 54 Fe isotope ratio of blood significantly correlates with total-body iron accumulation, severity of clinical disease, and the need for regular phlebotomies to prevent iron reaccumulation. We conclude that blood of patients with hereditary hemochromatosis contains more of the heavier iron isotopes than blood of healthy individuals. The primary determinant of the iron isotopic composition of blood appears to be isotope-sensitive iron absorption in the intestine and the efficiency of this process. (Blood. 2005;105:3812-3816)

Tumor Necrosis Factor-α −308G&gt;A Allelic Variant Modulates Iron Accumulation in Patients with Hereditary Hemochromatosis

“…Of 86 hemochromatosis patients included in the study, 73 presented with clinical manifestations and 13 were identified by family screening. Some of the hemochromatosis patients were previously included in a study investigating the iron isotope composition of blood (47 ).…”

“…We used atomic-absorption photometry to measure iron concentration in dry liver tissue from 30 patients and assessed hepatic iron index as iron concentration of dry liver tissue (mol/g) divided by the age of the patient (years). A total of 73 patients had completed iron depletion therapy at least 2 years before the study, and their need for iron removal to prevent reaccumulation was assessed from mean amounts of blood removed by phlebotomy per year during maintenance therapy (47 ).…”

“…Total body iron overload was assessed from the amount of blood removed by phlebotomy during depletion therapy, assuming that 500 mL of blood contains 250 mg of elemental iron (47,48 ). To evaluate all patients in the same way, although iron depletion therapy had been carried out according to different threshold values (Յ300 g/L) in our study patients, we used a ferritin concentration of 300 g/L as the threshold of depletion therapy.…”

Assessment of iron absorption in mice by ICP-MS measurements of 57Fe levels

“…[14]. Natural iron isotope variations in the blood may serve to identify differences in intestinal iron absorption between individuals and genotypes [15]. Moreover, 57 Fe and 58 Fe have already been used as tracers in nutritional studies on humans due to their low natural abundance [16,17,18].…”

Inductively coupled plasma- and glow discharge plasma-sector field mass spectrometry : Part II. Applications

“…244 Also for Zn, slight differences in the isotopic composition were demonstrated using MC-ICP-SFMS measurements between different body compartments. View Online owing to the fact that the production of 206 Pb, 207 Pb and 208 Pb as a result of the decay of 238 U, 235 U and 232 Th, respectively, has been going on for a much longer time in the crust.…”