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Hepatic iron overload: direct HFE (HLA-H) mutation analysis vs quantitative iron assays for the diagnosis of hereditary hemochromatosis.
- Source :
-
American journal of clinical pathology [Am J Clin Pathol] 1998 May; Vol. 109 (5), pp. 577-84. - Publication Year :
- 1998
-
Abstract
- Among patients with hepatic iron overload, the distinction between hereditary hemochromatosis (HH), a common yet treatable genetic disease, and other causes of siderosis remains problematic. The recent discovery of a specific homozygous mutation (C282Y) in a novel major histocompatibility complex class I-like gene (named HLA-H or HFE) in 80% to 100% of well-characterized cases of HH suggests that direct DNA-based mutation analysis may help resolve this dilemma. To assess the clinical utility of direct HLA-H mutation analysis in a typical diagnostic setting, we measured genotypic and phenotypic parameters of iron overload in 37 subjects with biopsy-proven hepatic siderosis (2+ or greater) and in 127 healthy control subjects. The prevalence of C282Y homozygotes was significantly greater in the hepatic siderosis group (32%) than in the control group (0%), confirming the association between this homozygous mutation and hepatic iron overload. In the hepatic siderosis group, C282Y homozygotes had significantly higher hepatic iron and ferritin levels, a significantly lower prevalence of hepatitis C virus or alcoholic liver disease, but no significant difference in the saturation of serum transferrin. Of the 20 subjects with a hepatic iron index (HII) in the previously defined "hemochromatosis range" (>1.9), 9 (45%) were C282Y homozygotes. Of the 11 nonhomozygous subjects with an HII greater than 1.9 (presumed false-positive HIIs), 10 (91%) had hepatic cirrhosis compared with 3 of 9 (33%) homozygotes with an HII greater than 1.9 who had cirrhosis (P<.02). The HII thus has poor diagnostic specificity for predicting genotypic HH in patients with cirrhosis. We conclude that direct determination of the HLA-H C282Y genotype may be the single best diagnostic test for HH, particularly in patients with cirrhosis, for whom the HII is quite nonspecific.
- Subjects :
- Adult
Diagnosis, Differential
Female
Genotype
Hemochromatosis Protein
Heterozygote
Homozygote
Humans
Iron Overload etiology
Liver Cirrhosis etiology
Liver Cirrhosis, Alcoholic complications
Male
Middle Aged
DNA Mutational Analysis
HLA Antigens genetics
Hemochromatosis diagnosis
Hemochromatosis genetics
Histocompatibility Antigens Class I genetics
Iron analysis
Iron Overload diagnosis
Liver Diseases diagnosis
Membrane Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9173
- Volume :
- 109
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of clinical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 9576576
- Full Text :
- https://doi.org/10.1093/ajcp/109.5.577