IRON OVERLOAD
Iron overload is defined as excess stores of iron in the body. Excess iron is
deposited in organs throughout the body. The most notable organs with iron
deposition are the liver, heart, and endocrine glands. The resulting symptoms and
disease are related to specific organ damage. Iron overload, also known as
haemochromatosis is mostly a genetic disease. The most important causes
are hereditary haemochromatosis (HH or HHC) which is a genetic disorder,
and transfusional iron overload, which can result from repeated blood transfusions.
CAUSES OF IRON OVERLOAD
1. Increased iron absorption: this is seen in Hereditary (primary)
haemochromatosis, ineffective erythropoiesis, e.g. thalassaemia intermedia or
myelodysplastic syndromes, chronic liver disease
2. Increased iron intake: Seen in African siderosis (dietary and genetic
components)
3. Repeated red cell transfusions
CLASSIFICATION OF IRON OVERLOAD
A. PRIMARY IRON OVERLOAD: (Haemochromatosis)
1. Hereditory haemochromatosis: excessive absorption of iron from the
gastrointestinal tract leading to iron overload
2. Aceruloplasminaemia: A disorder in which iron gradually accumulates in the
brain and various internal organs due to mutations in the caeruloplasmin gene
3. Congenital atransferinaemia: Caused by transferrin deficiency leading to
microcytic hypochromic red cells
4. Neonatal haemochromatosis: Severe liver disease in new born which is
accompanied by extrahepatic siderosis.
B. SECONDARY IRON OVERLOAD: (Haemosiderosis)
1. Dietary iron overload
2. Parenteral iron overload
3. Iron loading anaemias: Seen ineffective erythropoiesis, low hepcicd level and
excessive iron absorption, leading to secondary iron overload
4. Long term haemodialysis
Hereditory haemochromatosis has four types: The majority of cases are of Type 1,
involving the HFE gene.3). Types 1, 2 and 3 HH are autosomal recessive diseases
and share common features due to hepcidin deficiency, including high transferrin
saturation and hepatocyte iron accumulation. Type 4 HH, inherited as an autosomal
dominant condition due to heterozygous missense mutations in the gene for the
iron exporter ferroportin, is a heterogeneous disease with variable clinical
phenotype.
METHODS OF ASSESSING IRON OVERLOAD
1. Serum ferritin: This test is widely available, relatively inexpensive, and repeated
measurements are possible. However, serum ferritin is elevated during
inflammation, infection, and deficiency of ascorbate.
2. Liver biopsy for quantitation of iron: This is considered as the gold standard as it
correlates well with body iron stores. Simultaneous assessment of liver histology
(fibrosis, inflammation) is possible. The test is invasive with risk of intra-
abdominal bleeding.
3. Superconducting quantum interference device (SQUID) for liver iron load: This
test is very expensive and has very limited availability.
4. Imaging: Magnetic resonance imaging (MRI) is used as a noninvasive method
to estimate iron deposition levels in the liver and heart, which may aid in
determining a response to treatment or prognosis. Liver elastography has limited
utility in detecting liver fibrosis in hemochromatosis
TREATMENT
1. Phlebotomy or venesection is the mainstay of treatment in iron overload,
consisting of regularly scheduled blood draws to remove red blood cells (and iron)
from the body
2. Diet: The human diet contains iron in two forms: heme iron and non-heme iron.
Heme iron is usually found in red meat, whereas non-heme iron is found in plant
based sources. Heme iron is the most easily absorbed form of iron
3. Medication: There are chelating agents available for use for those unable to
tolerate routine blood draws. The drug deferoxamine binds with iron in the
bloodstream and enhances its elimination in 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 (and, thus, who develop
iron overload as a result) are deferasirox and deferiprone.
PROGNOSIS
In general, provided there has been no liver damage, patients should expect a
normal life expectancy if adequately treated by venesection. If the serum ferritin is
greater than 1000 ug/L at diagnosis, there is a risk of liver damage and cirrhosis
which may eventually shorten their life.
