In medicine, iron overload indicates accumulation of iron in the body from any cause. The most
important causes are hereditary haemochromatosis, a genetic disorder, and transfusional iron
overload, which can result from repeated blood transfusion.
Signs and symptoms Organs commonly affected by haemochromatosis
are the liver, heart, and endocrine glands. Haemochromatosis may present with the following
clinical syndromes: Cirrhosis of the liver
Diabetes due to pancreatic islet cell failure Cardiomyopathy
Arthritis Testicular failure
Tanning of the skin Joint pain and bone pain
Causes The causes can be distinguished between primary
cases and less frequent secondary cases. People of Celtic, British, and Scandinavian origin
have a particularly high incidence of whom about 10% are carriers of the gene and 1%
suffer from the condition. Primary haemochromatosis
Although it was known for most of the 20th century that most cases of haemochromatosis
were inherited, they were incorrectly assumed to depend on a single gene. 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", "non-HFE related hereditary haemochromatosis", or "non-HFE haemochromatosis".
Most types of hereditary haemochromatosis have autosomal recessive inheritance, while
type 4 has autosomal dominant inheritance. Secondary haemochromatosis
Severe chronic haemolysis of any cause, including intravascular haemolysis and ineffective erythropoiesis
Multiple frequent blood transfusions, which are usually needed either by individuals with
hereditary anaemias or by older patients with severe acquired anaemias such as in myelodysplastic
syndromes Excess parenteral iron supplements, such as
what can acutely happen in iron poisoning 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, steatohepatitis of any cause, porphyria
cutanea tarda, prolonged haemodialysis, and post-portacaval shunting.
Diagnosis There are several methods available for diagnosing
and monitoring iron loading including: Serum ferritin
Liver biopsy HFE
MRI Serum ferritin testing is a low-cost, readily
available, and minimally invasive method for assessing body iron stores. However, the major
problem with using it as an indicator of iron overload is that it can be elevated in a range
of other medical conditions unrelated to iron levels including infection, inflammation,
fever, liver disease, renal disease, and cancer. Also, total iron binding capacity may be low,
but can also be normal. The standard of practice in diagnosis of haemochromatosis
was recently reviewed by Pietrangelo. Positive HFE analysis confirms the clinical diagnosis
of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores,
or for predictive testing of individuals with a family history of haemochromatosis. The
alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis;
a negative report for HFE gene does not rule out haemochromatosis. In a patient with negative
HFE gene testing, elevated iron status for no other obvious reason, and family history
of liver disease, additional evaluation of liver iron concentration is indicated. In
this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic
examination of a liver biopsy. Assessment of the hepatic iron index is considered the
"gold standard" for diagnosis of haemochromatosis. Magnetic resonance imaging is emerging as
a noninvasive alternative to accurately estimate iron deposition levels in the liver as well
as heart, joints, and pituitary gland., Screening
Family members of those with primary haemochromatosis should be screened to determine if they are
a carrier or if they could develop the disease. This can allow preventative measures to be
taken. Screening the general population is not recommended.
Treatment Routine treatment in an otherwise-healthy
person consists of regularly scheduled phlebotomies. 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 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 bloodstream and enhances its elimination via urine and faeces. Typical treatment for
chronic iron overload requires subcutaneous injection over a period of 8–12 hours daily.
Two newer iron chelating drugs that are licensed for use in patients receiving regular blood
transfusions to treat thalassaemia are deferasirox and deferiprone.
Prognosis A third of those untreated develop hepatocellular
carcinoma. Affected individuals over age 40 or who have high serum ferritin levels are
at risk for developing cirrhosis. Significant problems occur in around one in ten.
Epidemiology It is most common in white people and occurs
in 0.6% of the population. Men who have the disease get symptoms from too much iron 24-fold
more times more often than women. Terminology
Historically, the term haemochromatosis was initially used to refer to what is now more
specifically called haemochromatosis type 1. Currently, haemochromatosis is mostly defined
as iron overload with a hereditary/primary cause, or originating from a metabolic disorder.
However, the term is currently also used more broadly to refer to any form of iron overload,
thus requiring specification of the cause, for example, hereditary haemochromatosis.
Hereditary haemochromatosis is an autosomal recessive disorder with estimated prevalence
in the population of 1 in 200 among patients with European ancestry, with lower incidence
in other ethnic groups. The gene responsible for hereditary haemochromatosis is located
on chromosome 6; the majority of hereditary haemochromatosis patients have mutations in
this HFE gene. Hereditary haemochromatosis is characterized by an accelerated rate of
intestinal iron absorption and progressive iron deposition in various tissues that typically
begins to be expressed in the third to fifth decades of life, but may occur in children.
The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy,
diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disorder
if left untreated, and recognizing that treatment is relatively simple, early diagnosis before
symptoms or signs appear is important. In general, 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 instead.
Other definitions distinguishing haemochromatosis or haemosiderosis that are occasionally used
include: Haemosiderosis is haemochromatosis caused
by excessive blood transfusions, that is, haemosiderosis is a form of secondary haemochromatosis.
Haemosiderosis is haemosiderin deposition within cells, while haemochromatosis is haemosiderin
within cells and interstitium. Haemosiderosis is iron overload that does
not cause tissue damage, while haemochromatosis does.
Haemosiderosis is arbitrarily differentiated from haemochromatosis by the reversible nature
of the iron accumulation in the reticuloendothelial system.
See also Human iron metabolism
References
Further reading Dlouhy, Adrienne C.; Outten, Caryn E.. "Chapter
8 The Iron Metallome in Eukaryotic cells". In Banci, Lucia. Metallomics and the Cell.
Metal Ions in Life Sciences 12. Springer. doi:10.1007/978-94-007-5561-1_8. ISBN 978-94-007-5560-4.
electronic-book ISBN 978-94-007-5561-1 ISSN 1559-0836 electronic-ISSN 1868-0402
Rodot, S; Lacour, JP; Dageville, C; Castanet, J; Boutté, P; Ortonne, JP. "["Bronze baby"
syndrome].". Annales de dermatologie et de venereologie 121: 568–70. PMID 7755316.
External links
Iron Overload.org Haemochromatosis.org
UK Haemochromatosis Society Haemochromatosis.org.au
Haemochromatosis Society of South Africa Canadian Hemochromatosis Society
GeneReviewNIH/UW entry on HFE-Associated Hereditary Hemochromatosis
Iron Overload Iron Overload - Hemosiderosis - Hemochromatosis
GeneReviewNIH/UW entry on TFR2-Related Hereditary Hemochromatosis
GeneReviewNIH/UW entry on Juvenile Hereditary Hemochromatosis
GeneReviewNIH/UW entry on Aceruloplasminemia FerriScan - MRI-based test to measure iron
overload