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Pathology - Hereditary hemochromatosis
Definition: An inherited condition marked by heightened intestinal iron absorption, resulting in iron accumulation in several organs, especially the liver, and potentially causing organ damage.
Epidemiology • The genetic incidence of the mutant gene is 0.4% among Caucasian populations, however the clinical penetrance is far lower. • Both males and females are equally affected; however, women typically present later in life due to iron loss associated with menstruation.
Genetics: An autosomal recessive condition resulting from mutations in the HFE gene located on chromosome 6p. • HFE encodes the iron regulating hormone hepcidin. • The most prevalent mutation is a missense mutation at codon 282, resulting in the substitution of a cysteine residue with a tyrosine (C282Y).
Pathogenesis • Hepcidin regulates plasma iron levels by obstructing iron export via ferroportin from duodenal enterocytes and macrophages. • A deficiency in hepcidin leads to elevated plasma iron levels and buildup in several organs, including the liver, pancreas, heart, joints, and pituitary gland
.
Presentation • Initial symptoms are nonspecific and encompass fatigue and arthropathy. • Subsequently, manifestations may include skin pigmentation, cirrhosis, hypogonadism, heart failure, and diabetes mellitus. • If transferrin saturation and serum ferritin levels are elevated, testing for the C282Y mutation should be conducted.
Macroscopy • Advanced instances result in diffuse nodularity attributable to cirrhosis.
Histopathology • The initial histological alteration is the deposition of iron in periportal hepatocytes, as seen by Perl’s stain. As the disease advances, iron accumulates in hepatocytes throughout the liver lobules, accompanied by portal tract enlargement due to fibrosis. • Ultimately, bridging fibrosis ensues, culminating in cirrhosis.
Prognosis: Overall mortality is not elevated in patients who receive prompt diagnosis and appropriate iron depletion therapy. Approximately 5% of men and 1% of women develop cirrhosis. This condition has a poorer prognosis, even with intervention, and poses a substantial risk of hepatocellular carcinoma.
Definition: An inherited condition marked by heightened intestinal iron absorption, resulting in iron accumulation in several organs, especially the liver, and potentially causing organ damage.
Epidemiology • The genetic incidence of the mutant gene is 0.4% among Caucasian populations, however the clinical penetrance is far lower. • Both males and females are equally affected; however, women typically present later in life due to iron loss associated with menstruation.
Genetics: An autosomal recessive condition resulting from mutations in the HFE gene located on chromosome 6p. • HFE encodes the iron regulating hormone hepcidin. • The most prevalent mutation is a missense mutation at codon 282, resulting in the substitution of a cysteine residue with a tyrosine (C282Y).
Pathogenesis • Hepcidin regulates plasma iron levels by obstructing iron export via ferroportin from duodenal enterocytes and macrophages. • A deficiency in hepcidin leads to elevated plasma iron levels and buildup in several organs, including the liver, pancreas, heart, joints, and pituitary gland
.
Presentation • Initial symptoms are nonspecific and encompass fatigue and arthropathy. • Subsequently, manifestations may include skin pigmentation, cirrhosis, hypogonadism, heart failure, and diabetes mellitus. • If transferrin saturation and serum ferritin levels are elevated, testing for the C282Y mutation should be conducted.
Macroscopy • Advanced instances result in diffuse nodularity attributable to cirrhosis.
Histopathology • The initial histological alteration is the deposition of iron in periportal hepatocytes, as seen by Perl’s stain. As the disease advances, iron accumulates in hepatocytes throughout the liver lobules, accompanied by portal tract enlargement due to fibrosis. • Ultimately, bridging fibrosis ensues, culminating in cirrhosis.
Prognosis: Overall mortality is not elevated in patients who receive prompt diagnosis and appropriate iron depletion therapy. Approximately 5% of men and 1% of women develop cirrhosis. This condition has a poorer prognosis, even with intervention, and poses a substantial risk of hepatocellular carcinoma.
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