Clinical and Biochemical Abnormalities in People Heterozygous for Hemochromatosis

Bulaj, Zaneta J.; Griffen, Linda M.; Jorde, Lynn B.; Edwards, Corwin Q.; Kushner, James P.

doi:10.1056/nejm199612123352403

Cited by 266 publications

(194 citation statements)

References 26 publications

(25 reference statements)

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“…35,36 The mean serum iron concentrations, ferritin levels and transferrin-saturation values were higher in heterozygous subjects than in normal ones, as were mean haemoglobin levels and mean corpuscular volume. The prevalence of iron deficiency anaemia was lower in women who carried HFE mutations.…”

Section: Discussionmentioning

confidence: 93%

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

et al. 2002

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Section: Discussionmentioning

confidence: 93%

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

et al. 2002

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“…In our control group we included heterozygote siblings of individuals with haemochromatosis because earlier studies have shown that heterozygotes for HFE mutations have only slightly higher iron indices than wild-types and are not affected by the morbidities attendant with homozygosity [16,36], and do not exhibit abnormalities in insulin resistance or secretion [37]. The study of mouse models of haemochromatosis also suggests that iron overload and not the HFE mutations per se are responsible for the glucose homeostasis phenotype [15], and the heterozygous controls in this study did not have elevated serum ferritin concentrations.…”

Section: Discussionmentioning

confidence: 99%

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

et al. 2006

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Aims/hypothesis: The prevalence and mechanisms of diabetes in hereditary haemochromatosis are not known. We therefore measured glucose tolerance, insulin secretory capacity and insulin sensitivity in adults with haemochromatosis.Subjects and methods: Subjects recruited from referrals to a haemochromatosis clinic underwent OGTT and frequently sampled IVGTT. A chart review of former clinic patients was also performed. Results: The prevalence of diabetes (23%) and IGT (30%) was increased in haemochromatosis compared with matched control subjects (0% diabetes and 14% IGT). Subjects with haemochromatosis and diabetes were overweight (14%) or obese (86%). The prevalence of diabetes, as determined by chart review of fasting glucose values, in subjects who had haemochromatosis and were in the 40-79 years age range was 26%. Overall, patients with haemochromatosis and control subjects had similar values for acute insulin response to glucose and insulin sensitivity. However, patients with haemochromatosis and IGT had a 68% decrease in acute insulin response to glucose (p<0.02) compared with those with NGT. They were not insulin-resistant, exhibiting instead a 62% increase in insulin sensitivity (NS). Haemochromatosis subjects with diabetes exhibited further declines in acute insulin response to glucose, insulin resistance, or both.Conclusions/interpretation: Diabetes and IGT are common in haemochromatosis, justifying screening for diabetes and therapeutic phlebotomy. The major abnormality associated with IGT is decreased insulin secretory capacity. Diabetes is usually associated with obesity and concomitant insulin resistance.

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“…It is characterised by an inappropriately increased absorption of dietary iron that leads to excess iron deposition in various tissues and organs [24]; it is inherited as an autosomal recessive trait linked to the major histocompatibility complex on the short arm of chromosome 6. Although severe iron overload is typical of homozygous hemochromatosis, minor modifications of serum iron, transferrinsaturation and serum ferritin can also be observed in a fraction of heterozygotes, but very rarely they give rise to complications [6]. However, the mild modifications of iron status induced by heterozygous hemochromatosis can influ-ence the severity and clinical evolution of heterogeneous conditions such as hepatitis [32], porphyria cutanea tarda [27] and cardiovascular disease [26].…”

Section: Introductionmentioning

confidence: 99%

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

Sampietro

Caputo

Casatta

et al. 2001

Neurobiology of Aging

104

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NEUROBIOL AGING. In the present study we analysed the genotype of HFE, the gene involved in hemochromatosis, in 107 patients with sporadic late-onset AD and in 99 age-matched non-demented controls. We observed that patients carrying the mutant HFE-H63D allele had a mean age at onset of 71.7 Ϯ 6.0 years versus 76.6 Ϯ 5.8 years of those who were homozygous for the wild-type allele (p ϭ 0.001). The frequency of the HFE-H63D mutation was highest (0.22) in the patients aged Ͻ70 years at the time of disease onset, whereas it was 0.12 in those with disease onset at an age of 70 -80 years, and 0.04 in those aged more than 80 years. The APOE genotype did not significantly modify the effect of HFE on age at onset. We conclude that mild disturbances of iron homeostasis associated with a common genetic determinant may interact with other pathogenic mechanisms involved in AD. HFE mutations may anticipate AD clinical presentation in susceptible individuals.

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Clinical and Biochemical Abnormalities in People Heterozygous for Hemochromatosis

Abstract: The phenotype of persons heterozygous for hemochromatosis differs from that of normal subjects, but complications due to iron overload alone in these heterozygotes are extremely rare.

Cited by 266 publications

References 26 publications

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

Association between the MHC class I gene HFE polymorphisms and longevity: a study in Sicilian population

High prevalence of abnormal glucose homeostasis secondary to decreased insulin secretion in individuals with hereditary haemochromatosis

The hemochromatosis gene affects the age of onset of sporadic Alzheimer’s disease

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