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Hemochromatosis Baghbanian M MD. Genetic Diseases – Hemochromatosis - Normal Iron Balance. Ingested 10-20 mg/day. Absorbed 1-2 mg/day. Lost Gut, skin, urine - 1-2 mg/day Menses - 30 mg/month. Andrews NC, New Engl J Med 1999; 341:1986. Iron overload states. Classification.
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Hemochromatosis Baghbanian M MD.
Genetic Diseases – Hemochromatosis - Normal Iron Balance Ingested 10-20 mg/day Absorbed 1-2 mg/day Lost Gut, skin, urine - 1-2 mg/day Menses - 30 mg/month Andrews NC, New Engl J Med 1999; 341:1986
Iron overload states Classification Hereditary hemochromatosis • HH: HFE related • C282Y homozygosity • C282Y/H63D compound heterozygosity • Other mutations of HFE • HH: non-HFE related; other gene mutations • Juvenile hemochromatosis • Autosomal dominant hemochromatosis (Solomon Islands)
Iron overload states Classification Secondary iron overload • Iron-loading anemias ± transfusion • Thalassemia major • Sideroblastic anemia • Chronic hemolytic anemias • Dietary iron overload • Chronic liver diseases • Hepatitis C and B • Alcohol-induced liver disease • Porphyria cutanea tarda • Fatty liver disease
Genetic Diseases - Hemochromatosis - Clinical Manifestations Pituitary Gonadotropin deficiency Skin bronzing Cardiomyopathy Conduction disorders Cirrhosis Hepatocellular carcinoma Diabetes mellitus Bacteremia Testicular atrophy Arthropathy Arthritis Pseudogout
Diagnosis • Indirect serologic markers of iron stores: • Transferrin saturation (TS): serum iron divided by TIBC, multiplied by 100 • > 50 % for women or > 60 % for men has a sensitivity of 0.92, specificity of 0.93, and PPV of 86 % • Saturation cutoff of 45 % used in screening recommendations
Diagnosis • Liver Biopsy: • Definitive diagnostic test of iron overload • Allows histochemical assessment of iron stores, measurement of hepatic iron concentration (HIC), detection of cirrhosis, and determination of disease stage • Qualitative hepatic iron determination with Perl’s staining • Quantitative confirmation of iron stores with HIC measurement
Target population Symptomatic Asymptomatic Adult 1st degree Relative of HH Fasting transferrin saturation & serum ferritin Step 1 TS < 45 percent & normal ferritin TS ≥ 45 percent & ferritin elevated No further iron evaluation Genotype Step 2
Target population TS<45 percent & normal ferritin TS<45 percent & ferritin elevated Genotype No further iron evaluation Step 2 C282Y/C282Y Compound heterozygote C282Y/H63D Heterozygote C282Y OR non-C282Y Age<40 years Ferritin<1000 AND normal ALT/AST Age>40 years and/or Ferritin>1000 Or elevated ALT/AST
Target population Compound heterozygote C282Y/H63D Heterozygote C282Y OR non-C282Y Age<40 years Ferritin<1000 AND normal ALT/AST Age>40 years and/or Ferritin>1000 Or elevated ALT/AST Exclude other liver or hematologic diseases. ±Liver biopsy Therapeutic phlebotomy Liver biopsy for HIC and histopathology Step 3 ± +
RJ: Liver Biopsy RJ: Liver Biopsy Quantitative liver iron = 300 mmole/g dry weight Iron index = 300 divided by 60 years of age = 5
Results of therapeutic phlebotomy in patients with hemochromatosis
Results of therapeutic phlebotomy in patients with hemochromatosis