Hereditary Hemochromatosis
Matthew M. Yeh, MD, PhD
Key Facts
Etiology/Pathogenesis
Mutation in HFE gene (C282Y and H63D) or non-HFE gene
Clinical Issues
Classic triad: Cirrhosis, diabetes, skin pigmentation
Microscopic Pathology
Deposition of iron in periportal hepatocytes in early phases of disease
Positive iron stain highlights pigment accumulation
Fibrosis begins as periportal, may progress to cirrhosis
Top Differential Diagnoses
Anemia of chronic disease
Transfusion-related hemosiderosis
Chronic hemolytic disorders
Nonspecific iron accumulation in any chronic liver disease
 Coarse and refractile iron granules  are readily discernible within the hepatocytes and bile duct epithelium in a case of hereditary hemochromatosis. |
 The iron deposition is confirmed by a Perl iron stain. |
TERMINOLOGY
Abbreviations
Hereditary hemochromatosis (HH)
Definitions
Disorder of iron metabolism inherited as autosomal recessive trait
ETIOLOGY/PATHOGENESIS
Genetic Mutations
2 most common mutations are in HFE gene
C282Y
H63D
Non-HFE mutations also occur
CLINICAL ISSUES
Epidemiology
Incidence
C282Y/C282Y genotype
80-85% of phenotypic HH in adults
C282Y/H63D genotype
5% of phenotypic HH in adults
Mutations in TfR2 or ferroportin-1 genes
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