Iron overload

Micrograph of hemosiderosis. Liver biopsy. Iron stain.
ICD-10	R79.0
ICD-9	790.6
DiseasesDB	5581
MeSH	D019190

In medicine, iron overload (also known as haemochromatosis) indicates accumulation of iron in the body due to any cause.

Contents 1 Terminology 2 Clinical presentation 3 Causes 3.1 Primary haemochromatosis 3.2 Secondary haemochromatosis 4 Treatment 5 See also 6 References 7 External links

[edit] Terminology

Historically, the term "haemochromatosis" was initially used to refer to what is now more specifically called haemochromatosis type 1 (or HFE-related hereditary haemochromatosis). The term is currently used more broadly to refer to any form of iron overload, thus requiring specification of the cause. The term haemosiderosis is used to indicate the pathological effect of iron accumulation in any given organ, which mainly occurs in the form of haemosiderin; sometimes the simpler term siderosis is used in its stead. The terms haemosiderosis and siderosis tend to be used when iron accumulation occurs only in a specific organ (such as the lung) as opposed to the whole body in haemochromatosis.

[edit] Clinical presentation

Organs commonly affected by haemochromatosis are the liver, heart and endocrine glands.^[1]

[edit] Causes

The causes can be distinguished between primary cases (genetically determined) and less frequent secondary cases (acquired during life).^[2]

[edit] Primary haemochromatosis

The fact that most cases of haemochromatosis were inherited was well known for most of the 20th century, though they were incorrectly assumed to depend on a single gene.^[3] The overwhelming majority actually depend on mutations of the HFE gene discovered in 1996, but since then others have been discovered and sometimes are grouped together as "non-classical hereditary haemochromatosis"^[4], "non-HFE related hereditary haemochromatosis".^[5], or "non-HFE haemochromatosis".^[6]

Description	OMIM	Mutation
haemochromatosis type 1: "classical"-haemochromatosis	235200	HFE
Haemochromatosis type 2A: juvenile haemochromatosis	602390	haemojuvelin ("HJV", also known as RGMc and HFE2)
Haemochromatosis type 2B: juvenile haemochromatosis	606464	hepcidin antimicrobial peptide (HAMP) or HFE2B
Haemochromatosis type 3	604250	transferrin receptor-2 (TFR2 or HFE3)
Haemochromatosis type 4/ African iron overload	604653	ferroportin (SLC11A3/SLC40A1)
Neonatal haemochromatosis	231100	(unknown)
Acaeruloplasminemia (very rare)	604290	caeruloplasmin
Congenital atransferrinaemia (very rare)	209300	transferrin
GRACILE syndrome (very rare)	603358	BCS1L

Most types of hereditary haemochromatosis have autosomal recessive inheritance, while type 4 has autosomal dominant inheritance.^[7]

[edit] Secondary haemochromatosis

• Severe chronic haemolysis of any cause, including intravascular haemolysis and ineffective erythropoiesis (haemolysis within the bone marrow).
• Multiple frequent blood transfusions (either whole blood or just red blood cells), which are usually needed either by individuals with hereditary anaemias (such as beta-thalassemia major, sickle cell anaemia, and Diamond-Blackfan anaemia) or by older patients with severe acquired anaemias such as in myelodysplastic syndromes.
• Excess parenteral iron supplements
• Excess dietary iron
• Some disorders do not normally cause haemochromatosis on their own, but may do so in the presence of other predisposing factors. These include cirrhosis (especially related to alcohol abuse), steatohepatitis of any cause, porphyria cutanea tarda, prolonged haemodialysis, post-portacaval shunting.

[edit] Treatment

Routine treatment in an otherwise healthy person consists of regularly scheduled phlebotomies (bloodletting). When first diagnosed, the phlebotomies may be fairly frequent, perhaps as often as once a week, until iron levels can be brought to within normal range. Once iron (Fe) and other markers are within the normal range, phlebotomies may be scheduled every other month or every three months depending upon the patient's rate of iron loading.

For those unable to tolerate routine blood draws, there is a chelating agent available for use. The drug Deferoxamine binds with iron in the blood stream and enhances its elimination via urine and feces. Typical treatment for chronic iron overload requires subcutaneous injection (SQ) over a period of 8-12 hours daily.

[edit] See also

• Human iron metabolism

[edit] References

[edit] External links

• Iron Overload (Texas Medical Center)
• Iron Overload - Hemosiderosis - Hemochromatosis (Merck)
• Iron Overload.org
• haemochromatosis.org
• Haemochromatosis.org.au

v • d • e Inborn error of metal metabolism (E83, 275) Transition metal Cu high: Copper toxicity · Wilson's disease deficiency: Copper deficiency · Menkes disease Fe high: Primary iron overload disorder: Hemochromatosis/HFE1 · Juvenile/HFE2 · HFE3 · African iron overload/HFE4 · Aceruloplasminemia · Atransferrinemia · Hemosiderosis deficiency: Iron deficiency Zn high: Zinc toxicity deficiency: Acrodermatitis enteropathica Electrolyte PO43− high: Hyperphosphatemia deficiency: Hypophosphatemia · alkaline phosphatase (Hypophosphatasia) Mg2+ high: Hypermagnesemia deficiency: Hypomagnesemia Ca2+ high: Hypercalcaemia · Milk-alkali syndrome (Burnett's) · Calcinosis (Calciphylaxis, Calcinosis cutis) · Calcification (Metastatic calcification, Dystrophic calcification) deficiency: Hypocalcaemia · Osteomalacia · Pseudohypoparathyroidism (Albright's hereditary osteodystrophy) · Pseudopseudohypoparathyroidism see also metal metabolism

v • d • e Abnormal clinical and laboratory findings for blood tests (R70-R79, 790) Red blood cells Size Macrocyte · Microcyte · Anisocytosis Shape (Poikilocyte) membrane abnormalities: Acanthocyte · Codocyte · Ovalocyte · Spherocyte trauma: Dacrocyte · Schistocyte Inclusion bodies developmental organelles (Howell-Jolly body, Basophilic stippling, Pappenheimer bodies, Cabot rings) abnormal hemoglobin precipitation (Heinz body) Other Rouleaux · Reticulocyte · Elevated ESR Lymphocytes Smudge cell · Downey cell Small molecules blood sugar: Abnormal glucose tolerance test · Hyperglycemia · Impaired glucose tolerance · Prediabetes nitrogenous: Azotemia · Hyperuricemia · Hypouricemia Proteins Elevated transaminases · Elevated alkaline phosphatase · Elevated cardiac markers · Elevated alpha-fetoprotein · Hypoproteinemia (Hypoalbuminemia) Minerals Iron overload disorder Pathogens/sepsis Bacteremia · Viremia · Fungemia · Parasitemia · Algaemia see also blood tests