Differential diagnosis of hereditary hemochromatosis from other liver disorders by genetic analysis: gene mutation analysis of patients previously diagnosed with hemochromatosis by liver biopsy.
BACKGROUND
Hereditary hemochromatosis, a common autosomal recessive trait caused by mutations in the HLA-H gene, is often diagnosed by the pathologist at the time of histologic examination. Unfortunately, histologic parameters alone do not differentiate between hereditary hemochromatosis and other causes of iron overload. We performed a retrospective study to determine the frequency of familial hemochromatosis in patients diagnosed with he mochromatosis by abnormal liver histology.


RESULTS
DNA was isolated from paraffin-embedded tissue sections from 15 patients and used in a polymerase chain reaction-based assay in which we tested for the C282Y and H63D mutations. We found that in this group of patients, 5 (33%) were homozygous for the common C282Y genetic mutation, 3 (20%) were heterozygous, and 7 (47%) were normal.


CONCLUSIONS
Our study shows that the molecular assay is the gold standard for the diagnosis of hereditary hemochromatosis. The case study also illustrates that a definitive diagnosis of familial hemochromatosis has significant counseling implications allowing for accurate family studies.
Bartolo
C
C
Department of Pathology, The Ohio State University, Columbus 43210, USA.
McAndrew
P E
PE
Sosolik
R C
RC
Cawley
K A
KA
Balcerzak
S P
SP
Brandt
J T
JT
Prior
T W
TW
D000328:Adult; D000368:Aged; D001706:Biopsy; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008107:Liver Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction