Hemochromatosis: Causes

Pathogenesis (disease development)

In hemochromatosis, there is an abnormal deposition of iron in the body. This is either due to a genetic defect (inherited in an autosomal recessive manner (4(5) types are distinguished today, with type 1 (mutation in the HFE gene) being the most common in Europe) or arises from another underlying disease. The normal iron content of the body is 3-4 g. Daily losses (1-1.5 mg/day) are usually compensated by iron absorption through the intestinal mucosa. However, in hemochromatosis, significantly more iron is absorbed, which cannot be compensated even by increased excretion. For this reason, progressive iron deposition occurs, especially in the liver, pancreas (pancreas), and heart.

Etiology (causes)

Biographic causes

  • Genetic burden
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: HFE
        • SNP: rs1800562 in the gene HFE
          • Allele constellation: AG (carrier of hemochromatosis).
          • Allele constellation: AA (causes hemochromatosis).
        • SNP: rs1799945 in the gene HFE.
    • Genetic diseases
      • Acoeruloplasminemia – genetic disease with both autosomal recessive and autosomal dominant inheritance; absence of the protein coeruloplasmin; in the course of the disease, failure of the oxidation of Fe2+ to Fe3+ leads to increased accumulation of toxic divalent iron in the body, esp. in the brain, liver and pancreas (pancreas), but also in other organs and tissues; often clinical triad: retinal degeneration (degeneration of the retina; about 93%), diabetes mellitus (about 89%) and neurological symptoms (about 73%) such as ataxia, involuntary movements and dementia; anemia (anemia; about 80%) is also common.
      • Hereditary hemochromatosis (iron storage disease) – genetic disease with autosomal recessive inheritance with increased deposition of iron as a result of increased iron concentration in the blood with tissue damage.
      • Congenital atransferrinemia (synonym: hypotransferrinemia) – genetic disorder with autosomal recessive inheritance leading to transferrin (TF) deficiency; symptoms include microcytic hypochromic anemia (anemia; with pallor, lassitude, and retarded growth) and iron overload, which can lead to death if untreated.
      • Thalassemia – autosomal recessive hereditary synthesis disorder of the alpha or beta chains of the protein portion (globin) in hemoglobin (hemoglobinopathy)/thalassemia major (homozygous form of thalassemia; so-called Cooley anemia).

Causes related to disease

Blood, blood-forming organs – immune system (D50-D90).

  • Chronic hemolytic anemia – forms of anemia associated with destruction of red blood cells (RBCs).
  • Sideroblastic anemia – sideroblastic anemia, which is also called sideroachrestic anemia, is a special form of aplastic anemia (form of anemia (anemia) characterized by pancytopenia (reduction of all rows of cells in the blood; stem cell disease) and a concomitant hypoplasia (functional impairment) of the bone marrow).

Endocrine, nutritional and metabolic diseases (E00-E90).

  • Porphyria cutanea tarda – congenital or acquired metabolic disorder (enzymopathy).

Liver, gallbladder, and bile ducts-pancreas (pancreas) (K70-K77; K80-K87).

  • Hepatitis B (liver inflammation).
  • Hepatitis C (liver inflammation)
  • Cirrhosis – liver disease leading to a gradual connective tissue remodeling of the liver with functional impairment.
  • Non-alcoholic steatohepatitis

Neoplasms – tumor diseases (C00-D48)

  • Myelodysplastic syndrome (MDS) – acquired clonal disease of the bone marrow associated with a disorder of hematopoiesis (blood formation); defined by:
    • Dysplastic cells in the bone marrow or ring sideroblasts or an increase of myeloblasts up to 19%.
    • Cytopenias (decrease in the number of cells in the blood) in the peripheral blood count.
    • Exclusion of reactive causes of these cytopenias.

    One quarter of MDS patients develop acute myeloid leukemia (AML).

Psyche – Nervous System (F00-F99; G00-G99).

  • Alcohol abuse

Other causes

  • Iron overload in individuals from southern Africa.
  • Dietary iron overload
  • Neonatal iron overload – iron overload of the newborn.
  • Parenteral iron overload – iron overload by artificial nutrition through the vein.
  • Transfusion-related iron overload – iron overload caused by the transfusion of blood.