Hereditary Hemochromatosis

Dr. Craig Rosenstengle

1.       Hemochromatosis = Total body iron overload

A.       Type 1 Hereditary hemochromatosis – HFE gene

B.       Secondary iron overload (hemosiderosis) – Dyserythropoeisis, parenteral iron overload, and chronic liver disease are main drivers

2.       Iron Regulation

A.       Enterocytes in duodenum absorb iron

B.       Iron absorption regulated by hepcidin

C.       Hepcidin produced by liver, controlled by iron stores and inflammation

D.      No coordinated iron excretion in body

3.       Type Hereditary hemochromatosis

A.       HFE gene – creates protein involved in hepcidin regulation within hepatocytes

B.       C282Y homozygotes are majority of cases of hereditary hemochromatosis (85%)

C.       C282Y/H63D compromise small minority of cases

D.      H63D & C65S homozygotes and wild type heterozygotes do not lead to iron overload

4.       Classic presentation – unlikely to have all symptoms

A.       General – fatigue

B.       MSK – arthralgia particularly 2nd & 3rd MCP

C.       Liver – hepatomegaly, RUQ pain, possibly bridging fibrosis or cirrhosis

D.      Heart – conduction abnormalities or signs/symptoms of heart failure

E.       Endocrine – diabetes, hypogonadism (primary & secondary), or hypothyroidism

5.       Diagnosis

A.       Elevated ferritin above ULN or TSAT >45% consider HFE analysis

B.       Consider the whole picture when interpreting? Ie: co morbid inflammatory conditions; pre-test probability; symptomatology



6.       Management

A.       Phlebotomy treatment of choice

B.       Goal ferritin level 50 – 100 mg/L

C.       If Hb begins dropping with ferritin still elevated, consider alternative diagnosis

D.      No recommended diet, recommend against extra vitamin C & raw shellfish

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