Genetic hemochromatosis is a condition caused by excessive iron absorption in the intestines, leading to high levels of iron in the body's tissues and organs. If untreated, it can damage organs like the liver, heart, and pancreas. The main treatment is regular phlebotomy to reduce iron levels in the body. Dietary changes and medication may also be used to manage iron overload and related organ damage. It is often inherited in an autosomal recessive pattern and associated with mutations in the HFE gene.

1. GENETIC
HEMOCHROMATOSIS
BY:
Mr.Keerthi Samuel,
Asst.Professor,
Vijay Marie College of Nursing

2. DEFINITION
Hereditaryhaemochromatosis (or hemochromatosi
s is a genetic disorder characterized by excessive
intestinal absorption of dietary iron, resulting in a
pathological increase in total body iron
stores Humans, like most animals, have no means
to excrete excess iron.
It’s a condition that causes dangerously high levels
of iron build up in the body.
It’s present in approximately 4.5 out of 1000
individuals, but much more frequently in men.
If untreated, it can lead to organ failure or even
death!

3. DEFINITION
Excess iron accumulates in tissues and organs,
disrupting their normal function. The most
susceptible organs include the liver, adrenal
glands, heart, skin, gonads, joints, and the pancreas;
patients can present with cirrhosis, polyarthropathy,
adrenal insufficiency, heart failure, or diabetes.[6]
The disease is inherited in an autosomal recessive
pattern.
 Most often, the parents of an individual with an
autosomal recessive condition remain carriers.

4. ETIOLOGY
PRIMARY HEMOCHROMATOSIS:
Inherited
Mostly a single gene disorder
SECONDARY HEMOCHROMATOSIS:
 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), Ex:hereditary beta-thalassaemia major, sickle
cell anaemia,
 Excess parenteral iron supplements, like in iron poisoning
 Excess dietary iron
 predisposing factors like cirrhosis (especially related to alcohol
abuse), steatohepatitis of any cause, porphyria cutanea tarda,
prolonged haemodialysis, and post-portacaval shunting

5. GENETICS  One of the better-characterized genes responsible for
hereditary haemochromatosis is HFEon chromosome 6,
which codes for a protein that participates in the
regulation of iron absorption. The HFE gene has three
common mutations, C282Y, H63D and S65C. The
C282Y allele is a transition point
 mutation from guanine to adenine at nucleotide 845
in HFE, resulting in a missense mutation that replaces
the cysteine residue at position 282 with
a tyrosine amino acid.
 Heterozygotes for either allele can manifest clinical
iron overload, if they have two of any alleles. This
makes them compound heterozygous for
haemochromatosis and puts them greatly at risk of
storing excess iron in the body.

6. TRIAD OF
CARDINAL
SIGNS OF HHC
cirrhosis
bronze
skin
diabetes

7. CLINICAL
FEATURES
 The organs mostly affected are Liver, heart and endocrine
glands.
 Hemochromatosis may present with the following
syndromes:
• Chronic liver disease or cirrhosis.
• Heart failure or dysarrythmias.
• Hormonal issues- hypogonadism leading to infertility and
decreased libido in men
• Diabetes in people with iron overload occurs as a result of
selective iron deposition in islet beta cells in
the pancreas leading to functional failure and cell death.

8. CLINICAL FEATURES
 Bronzing of the skin. This deep tan
color, in concert with insulin
insufficiency due to pancreatic
damage, is the source of a nickname
for this condition: "bronze diabetes".
 Cardinal sign of hemochromatosis.

9. CLINICAL FEATURES
Arthritis from deposition of calcium
pyrophosphate in the joints leading to joint
painsespecially those of hands particularly
int the knucles of second and third fingers.

10. LESS
COMMON
SIGNS
• Deafness
• Dyskinesias, including Parkinsonian symptoms
• Dysfunction of certain endocrine organs:
• Parathyroid gland (leading to hypocalcaemia)
• Pituitary gland
• More commonly, a slate-grey or less commonly darkish
colour to the skin (see pigmentation, hence its name
"bronze diabetes" when it was first described by
Armand Trousseau in 1865)
• An increased susceptibility to certain infectious
diseases caused by siderophilic microorganisms:
• Vibrio vulnificus infections from eating seafood or
wound infection[16]

11. MORE
COMMON
SIGNS
• Fatigue, Malaise, Joint and bone pain.
• Liver cirrhosis (with an increased risk of hepatocellular
carcinoma.Clubbing,leukonychia,asterixis,hepatomegaly
palmar erythema, and spider naevi. Cirrhosis can also
present with jaundice and ascites.
• Insulin resistance (often, patients have already been
diagnosed with DM TYPE 2 due to pancreatic damage
from iron deposition.)
• Congestive heart failure, abnormal heart rhythms,
or pericarditis and decreased libido.
• Arthritis of the hands (especially the second and
third metacarpophalangeal joints, but also
the knee and shoulder joints
• Damage to the adrenal gland, leading to adrenal
insufficiency

12. • Long-term effects of haemochromatosis on these organs can be very serious, even fatal when untreated.
• For example, The liver is a primary storage area for iron and naturally accumulates excess iron. Over
time, the liver is likely to be damaged by iron overload.
• Cirrhosis itself may lead to additional and more serious complications, including bleeding from dilated
veins in the esophagus (esophageal varices) and stomach (gastric varices) and severe fluid retention in
the abdomen (ascites).
• Toxins may accumulate in the blood and eventually affect mental functioning. This can lead to confusion
or even coma (hepatic encephalopathy).
• Cirrhosis and haemochromatosis together can increase the risk of liver cancer
MULTI ORGAN DAMAGE

13. • The pancreas, which also stores iron, is very important in the body's mechanisms for
sugar metabolism. Diabetes affects the way the body uses blood sugar (glucose).
• Diabetes is, in turn, the leading cause of new blindness in adults and may be involved in kidney
failure and cardiovascular disease.
• If excess iron in the heart interferes with its ability to circulate enough blood, a number of problems can
occur, such as congestive heart failure and death. The condition may be reversible when
haemochromatosis is treated and excess iron stores are reduced.
• Arrhythmia or abnormal heart rhythms can cause heart palpitations, chest pain, and light-headedness,
and are occasionally life-threatening. This condition can often be reversed with treatment for
haemochromatosis.
• Bronze or grey coloration of the skin pigmentation is caused primarily by increased melanin deposition,
with iron deposition playing a lesser role Severity of periodontal disease is associated with high transferrin
saturation in haemochromatosis patients.
MULTI ORGAN DAMAGE

14. CLINICAL FEATURES

15. DIAGNOSTIC
FINDINGS
1. BLOOD TESTS:Serum ferritin testing is a low-cost, readily
available, and minimally invasive method for assessing body
iron stores. THIS CANALSO OCCUR IN infection,
inflammation, fever, liver disease, kidney disease, and cancer.
Also, total iron binding capacity may be low, but can also be
normal
2. DNA/screening: the standard of practice Positive HFE analysis
confirms the clinical diagnosis of haemochromatosis in
asymptomatic individuals with a family history of
haemochromatosis.. First degree relatives of those with primary
haemochromatosis should be screened for carrier status. This can
allow preventive measures to be taken.

16. DIAGNOSTIC
FINDINGS
3.Liver biopsy: can determine the cause of inflammation or
cirrhosis. In someone with negative HFE gene testing, elevated
iron status for no other obvious reason, and family history of
liver disease. In this case, diagnosis of haemochromatosis is
based on biochemical analysis and histologic examination of a
liver biopsy. Assessment of the hepatic iron index (HII) is
considered the "gold standard" for diagnosis of
haemochromatosis.
4. Magnetic resonance imaging (MRI) is used as a noninvasive
way to accurately estimate iron deposition levels in the liver as
well as heart, joints, and pituitary gland.

17. MANAGEMENT
 Routine treatment consists of regularly scheduled
phlebotomies (bloodletting or erythrocytapheresis).
 When first diagnosed, the phlebotomies may be performed
every week or fortnight, until iron levels can be brought to
within normal range.
 Once the serum ferritin and transferrin saturation are within
the normal range, treatments may be scheduled every two to
three months depending upon the rate of reabsorption of iron.
 A phlebotomy session typically draws between 450 and 500 mL
of blood.
PHLEBOTOMY

18. MANAGEMENT
 A diet low in iron is generally recommended, but has little effect
compared to venesection.
 The human diet contains iron in two forms: heme iron and non-heme
iron. Heme iron is the most easily absorbed form of iron. People with
iron overload may be advised to avoid food that are high in heme
iron.
 Highest in heme iron is red meat such as beef, venison, lamb,
buffalo, and fish such as bluefin tuna. A strict low-iron diet is usually
not necessary.
 Non-heme iron is not as easily absorbed in the human system and is
found in plant-based foods like grains, beans, vegetables, fruits,
nuts, and seeds.
 Organ damage:
 Treatment of organ damage (heart failure
with diuretics and ACE inhibitor therapy)
DIET

20. MANAGEMENT
 For those unable to tolerate routine blood draws, there
are chelating agents available for use.
 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 deferiproneof blood.
MEDICATION

21. MANAGEMENT
 Desferrioxamine mesylate:
Where venesection is not possible, long-term
administration of desferrioxamine mesylate is useful.
Desferrioxamine is an iron-chelating compound, and
excretion induced by desferrioxamine is enhanced by
administration of vitamin C. It cannot be used during
pregnancy or breast-feeding due to risk of defects in the
child.
MEDICATION