Hemochromatosis is a condition that leads to abnormal iron deposition in specific organs. There are two main types: primary (hereditary) and secondary (e.g., transfusion-related). The most common form is hereditary autosomal recessive hemochromatosis type 1, which is caused by an underlying genetic defect that results in partially uninhibited absorption of iron in the small intestine. Hemochromatosis is mostly asymptomatic but can become symptomatic, usually between the third and fifth decade of life, when poisonous levels of iron have had time to accumulate in the body. Symptoms include fatigue, hyperpigmentation, diabetes mellitus ("bronze diabetes"), and arthralgia. The deposits may lead to various organ diseases, the most typical being the development of liver cirrhosis, which is accompanied by an increased risk of hepatocellular carcinoma (HCC). Serum ferritin and transferrin saturation levels are typically elevated. Molecular genetic testing or a liver biopsy may be used to confirm the diagnosis. Treatment primarily consists of repeated phlebotomy to reduce iron levels. In addition, dietary changes and drug therapy (chelating agents such as deferoxamine) may be used to influence the amount of iron in the body.
- Prevalence: the most frequent genetic disease in the white population
- Age of onset: individuals > 40 years
Epidemiological data refers to the US, unless otherwise specified.
Primary (hereditary) hemochromatosis
- Classical and most frequent form: adult hemochromatosis type I
- Further forms: Hemochromatosis types II–IV are also hereditary, but significantly less frequent.
HLA A3 as in HA3mochromatosis!
- Caused by iron overload
Hemochromatosis type I
- The HFE gene regulates iron hemostasis (see “Iron” in the articles on ).
- HFE gene defect (homozygous) → defective binding of transferrin to its receptor → ↓ hepcidin synthesis by the liver → unregulated ferroportin activity in enterocytes → ↑ intestinal iron absorption → iron accumulation throughout the body → damage to the affected organs
In hereditary hemochromatosis, decreased hepcidin leads to iron overload. In secondary hemochromatosis, iron overload leads to increased hepcidin (unless liver fibrosis or cirrhosis, which leads to decreased hepcidin synthesis, is present)
- Asymptomatic: 75% of cases
- General symptoms: fatigue, lethargy
- Pancreas: signs of diabetes mellitus (polydipsia, polyuria)
- Skin: hyperpigmentation, bronze skin
- Pituitary gland: hypogonadism, erectile dysfunction, testicular atrophy, loss of libido, amenorrhea
- Joints: arthralgia (typically symmetrical arthropathy of the MCP joints II and III); , chondrocalcinosis (accumulation of calcium pyrophosphate)
As a result of its subtle and primarily asymptomatic course, hemochromatosis is often an incidental diagnosis first detected during routine checks or diagnosed only once signs of advanced organ involvement become apparent.
- ↑ Serum iron
- ↑ Ferritin in serum (> 200 μg/L)
- ↓ Total iron-binding capacity (TIBC)
- ↑ Transferrin saturation (> 45%)
- ↑ Liver enzymes (AST, ALT)
- First-degree relative with hemochromatosis
- Confirmed iron overload
- Findings: homozygote C282Y, homozygote H63D, or heterozygote C282Y/H63D mutations of the HFE gene confirm the diagnosis.
- MRI; : noninvasive way to estimate the iron concentration in the liver
- Chest x-ray and echocardiography: diagnose and monitor cardiac hemochromatosis
- Indications: elevated liver enzymes caused by hereditary hemochromatosis; increased serum ferritin levels (> 1000 μg/L)
- Dietary changes
Therapeutic phlebotomy (first-line treatment)
- Initially 1–2 phlebotomy sessions per week; after reaching target ferritin and hemoglobin levels, phlebotomy should be performed every 2–4 months.
- Target levels: serum ferritin 20–50 μg/L; hemoglobin > 12 g/dL (or 120 g/L)
- Prognosis: initiation of therapy in the pre-cirrhotic phase → normal life expectancy and no organ damage
- Drug-induced iron chelation
Drugs that delete iron (Fe) in hemochromatosis: deFeroxamine, deFerasirox, deFeriprone.