Long-term survival analysis in hereditary hemochromatosis

Adams, Paul C.; Speechley, Mark; Kertesz, Ann E.

doi:10.1016/0016-5085(91)90013-b

Cited by 221 publications

(134 citation statements)

References 6 publications

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“…When the disorder remains untreated, premature mortality resulting from hepatocellular carcinoma, cirrhosis, cardiomyopathy, or diabetes mellitus is common (2,3). Removal of iron and the prevention of its reaccumulation by phlebotomy treatment dramatically improves life expectancy in these patients (4)(5)(6)(7). The discovery of a tight linkage between HH and the HLA-A locus has led to the clarification of the genetic nature and the autosomal recessive inheritance of the disease (8,9).…”

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confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

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Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.

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mentioning

confidence: 99%

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Santos¹,

Schilham²,

Rademakers³

et al. 1996

The Journal of Experimental Medicine

181

View full text Add to dashboard Cite

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“…The clinical feaLong-term survival was significantly reduced in patients tures of this patient cohort has been previously described. [10][11][12] with heavy alcohol consumption (mean follow-up, 9.22 From this database, homozygotes were selected that had an years). This suggests that chronic alcohol consumption HLA identical sibling with hemochromatosis to establish a has an additive hepatotoxic effect despite the paucity of hereditary disorder of iron metabolism (n Å 105).…”

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confidence: 99%

“…Multiple stepwise linear regression analysis showed that both heavy alcohol consumption (P Å .04), sis is the major clinical factor affecting survival. 10,13 It is also possible that the higher iron burden in the pacirrhosis (P Å .02), and age (P Å .006) were major factors affecting long-term survival. Sex was not a signifi-tients with heavy alcohol consumption had an adverse effect on survival.…”

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confidence: 99%

Alcoholism in hereditary hemochromatosis revisited: Prevalence and clinical consequences among homozygous siblings

1996

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The relationship between alcoholism and hereditary hemochromatosis performed before the use of these dihemochromatosis remains controversial. Previous stud-agnostic tools most likely included patients with alcoies have included patients with alcoholic siderosis holic siderosis rather than hereditary hemochromatorather than hereditary hemochromatosis. In this retro-sis. [3][4][5][6][7][8][9] In this study, we have re-examined the spective study, the clinical features, iron status, alcohol prevalence of alcohol use in hereditary hemochromatohistory, liver histology, and long-term survival were re-sis using rigid criteria for the diagnosis, including the viewed in 105 homozygotes for hemochromatosis using presence of an HLA identical sibling with hemochromarigid diagnostic criteria including an HLA identical sib-tosis.ling with iron overload. Heavy alcohol consumption (ú80 g ethanol/day) was found in 15% of hemochromato-PATIENTS AND METHODS sis patients. Histological features of alcoholic liver disease (Mallory's hyaline bodies, pericentral fibrosis, polyPatient records were reviewed from a large database of 170 morphonuclear infiltrate, and fatty infiltration) were hemochromatosis homozygotes that have been documented uncommon in hemochromatosis. Hemochromatosis pa-since 1965. Family investigations at this center ranged from tients with heavy alcohol consumption had a higher no further investigation in the case of isolated proband cases prevalence of cirrhosis than hemochromatosis patients to extensive pedigree analysis involving up to 45 family memwithout heavy alcohol consumption. Hepatic iron con-bers of a single family over multiple generations. Data was centration and hepatic iron index did not significantly available on 483 family members assessed at this tertiary differ between these two hemochromatosis groups. referral center for possible hemochromatosis. The clinical feaLong-term survival was significantly reduced in patients tures of this patient cohort has been previously described. [10][11][12] with heavy alcohol consumption (mean follow-up, 9.22 From this database, homozygotes were selected that had an years). This suggests that chronic alcohol consumption HLA identical sibling with hemochromatosis to establish a has an additive hepatotoxic effect despite the paucity of hereditary disorder of iron metabolism (n Å 105). There were histological features of alcoholic liver disease. (HEPATOL-65 homozygotes excluded from this study because no HLA OGY 1996;23:724-727. ) identical sibling had been identified. The diagnosis was confirmed by liver biopsy results in all probands and most discovered siblings (n Å 89/105). No hemochromatosis patients hadThe clinical distinction between patients with heredconcomitant chronic viral hepatitis B or C on histological itary hemochromatosis and alcoholic siderosis contin-examination of the liver biopsy specimen. Liver biopsy reues to be a diagnostic problem. Clinical tools that have ports were reviewed for the presence of Mallory's hyaline, improved this diagnostic di...

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“…13,14 Patients with cirrhosis have a 5.5-fold relative risk of death compared to the noncirrhotic hemochromatosis patients. 15,16 HH can cause other complications such as primary liver cancer, diabetes mellitus or other endocrinopathy, arthropathy, cardiomyopathy, and reduced longevity, 17,18 but timely treatment can prevent many of these complications. 19 Routine screening for genetic disorders is controversial.…”

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confidence: 99%

Impact of hemochromatosis screening in patients with indeterminate results: The hemochromatosis and iron overload screening study

Anderson

Wenzel

Walker

et al. 2006

Genetics in Medicine

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Purpose: Assess the quality of life impact of receiving indeterminate test results for hemochromatosis, a disorder involving HFE genetic mutations and/or elevated serum transferrin saturation and ferritin. Methods: The study sample was from the Hemochromatosis and Iron Overload Screening Study, a large observational study of hemochromatosis among primary care patients in the US and Canada using HFE genotype and serum transferrin saturation and ferritin screening. Study subjects included 2,304 patients found with hemochromatosis risk of uncertain clinical significance.Assessed was SF-36 general health and emotional well-being before screening and six weeks after participants received their test results. Health worries were assessed after screening. Results: Of the study subjects, 1,268 participants (51.5%) completed both assessments. Compared to normal controls, those with HFE mutations or elevated serum transferrin saturation and ferritin levels of uncertain significance were more likely to report diminished general health and mental well-being, and more health worries. These effects were associated with participants' belief of having tested positive for hemochromatosis or iron overload. Conclusion: Notification of indeterminate results from screening may be associated with mild negative effects on well-being, and might be a potential participant risk in screening programs for disorders with uncertain genotype-phenotype. Genet Med 2006:8(11):681-687.

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Long-term survival analysis in hereditary hemochromatosis

Cited by 221 publications

References 6 publications

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.

Alcoholism in hereditary hemochromatosis revisited: Prevalence and clinical consequences among homozygous siblings

Impact of hemochromatosis screening in patients with indeterminate results: The hemochromatosis and iron overload screening study

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