Hemochromatosis, or iron overload, is a genetic disorder resulting in excessive iron absorption and storage in the body, primarily caused by mutations in the HFE gene. It can lead to severe complications affecting multiple organs, including the liver and heart, and is most common in individuals of Caucasian descent. Management involves phlebotomy and dietary modifications to reduce iron levels and prevent organ damage.

1. HEMOCHROMATOSIS
(IRON OVERLOAD)
BY
ANNIE CHULU MUNG’OMA 210400304
PATSON MWALE 210400341
TRICIA TIMBANI 210400245

2. HEMOCHROMATOSIS
• Hemochromatosis also known as iron overload is a genetic disorder
that affects the level of iron in the body causing excessive absorption
and storage of dietary iron in the body.
• Iron levels are regulated by absorption and excretion of excess iron
through the intestinal tract.
• This regulation of iron by the body is impaired in hemochromatosis as
a result of a genetic mutation, resulting in excessive iron absorption.
• Organs affected by hemochromatosis include the liver, pancreas,
heart, thyroid, joints, skin, gonads, and pituitary.

3. AETIOLOGY OF HEMOCHROMATOSIS
• Hemochromatosis is an iron storage disorder characterized by excessive
total body iron in body tissues. There are two main types of
hemochromatosis known:
• Primary hemochromatosis: also known as hereditary hemochromatosis. It
is caused by mutation of the HFE gene which controls how the body
absorbs iron.
• The HFE (hemochromatosis gene) is a gene found on the short arm of
chromosome 6.
• The two most common mutations are in the HFE genes are C28Y and H63D.
• Hereditary hemochromatosis is inherited as an autosomal recessive trait,
meaning that the individual must inherit two copies of the gene mutation
(one from each parent) to develop the condition.

4. • Hereditary hemochromatosis has four types, which include the
following:
i. Type 1: HFE-related hemochromatosis, caused by mutations of the
HFE gene which is responsible for the regulation of iron absorption.
ii. Type 2: Juvenile hemochromatosis, caused by mutation in the HJV
and HAMP genes. HJV gene affects the production of the protin
hemojuvelin, which in turn affects the production of hepcidin, a
protein that regulates iron intake. HAMP gene codes for the protein
hepcidin. It’s onset is usually at 15 to 20 years.
iii. Type 3: caused by mutation in the TFR2 gene that codes for the
protein transferrin receptor 2, which is responsible for the
regulation of iron intake. It’s onset is at 30 to 40 years.
iv. Type 4: ferroportin disease, caused by mutation in the SLC4OA1
gene which codes for the protein ferroportin, which is responsible
for the regulation of iron release from the cells. It’s onset is at 10 to
80 years. Type 4 is an autosomal dominant disease.

5. AETIOLOGY CONT’D
• Secondary hemochromatosis: occurs when a build up of iron stems
from another medical condition such as erythropoietic
hemochromatosis. In this condition the red blood cells release too
much iron into the blood because they are produced in excess.
• Secondary hemochromatosis is less common as compared to primary
hemochromatosis. Its risk factors include the following:
i. Alcohol dependency
ii. Family history of diabetes, heart disease or liver disease
iii. Taking iron or vitamin C supplements which increase the amount of
iron the body absorbs
iv. Frequent blood transfusions

6. EPIDEMIOLOGY
• Hemochromatosis is the most common genetic disorder in
Caucasians, affecting 1 in 200 to 1 in 300 individuals.
• The prevalence of hemochromatosis is high in:
i. Whites with European ancestry.
ii. Individuals with a family history f hemochromatosis.
iii. Men; have a higher chance of developing hemochromatosis than
women by fivefold.
iv. People with a higher intake of alcohol.
v. People with a family history of liver disease or arthritis.

7. PATHOPHYSIOLOGY
• Increased intestinal iron absorption: mutated genes lead to excessive
iron absorption.
• Iron overload: iron accumulation in organs and tissue, causing
damage.
• Inhibited hepcidin production: hepcidin, a hormone regulating iron
levels, is suppressed, allowing excessive iron absorption.
• Unregulated iron distribution: iron is deposited in organs like the liver,
heart, pancreas and joints, leading to damage and dysfunction.
• Oxidative stress and inflammation: iron accumulation triggers
oxidative stress, inflammation and tissue damage.
• Organ damage: prolonged iron overload lead to cirrhosis, liver cancer,
heart failure, diabetes and arthritis.

8. SIGNS AND SYMPTOMS
• Fatigue and weakness.
• Abdominal pain.
• Sexual problems (erectile dysfunction in men and amenorrhea in
women).
• Joint pain.
• Bronze discolouration.

9. COMPLICATIONS
• Hepatocellular carcinoma
• Diabetes mellitus
• Congestive heart failure
• Hypogonadism
• Osteoporosis
• Patients with iron overload are at increased risk of infection from
Yersinia enterocolitica, Listeria monocytogenes, and Vibrio vulnificus.

10. DIAGNOSIS
• Diagnosis is based on a combination of family history, laboratory tests
and imaging studies
• Serum ferritin is the initial investigation. High ferritin is indicative of
hemochromatosis.
• Transferrin saturation helps distinguish between high ferritin caused
by iron overload.
• Genetic testing for mutations in the HFE gene.
• Liver biopsy.
• MRI (gives a detailed picture and quantifies iron concentration in the
liver)

11. WHEN IS HEMOCHROMATOSIS USUALLY
DIAGNOSED?
Men: between the ages of 40 and 60
Women: after menopause, typically between the ages of 50 and 60
Type 2 hemochromatosis (juvenile-onset): symptoms often begin in
childhood, and by age 20, iron accumulation causes decreased or
absent secretion of sex hormones. If untreated, potentially fatal heart
disease becomes evident by age 30.
Type 3 hemochromatosis: symptoms generally begin before age 30

12. DIFFERENTIAL DIAGNOSIS
•
• On account of the involvement of multiple organ systems in hemochromatosis, the differential diagnoses are
also broad.
• Iron overload from chronic transfusion
• Hepatitis B and C
• Nonalcoholic fatty liver disease (NAFLD)
• Excessive iron supplementation
• Dysmetabolic hyperferritinemia
• Hereditary aceruloplasminemia
• Alcoholic liver disease
• Porphyria cutanea tarda
• Marrow hyperplasia
• Hemolytic anemia
• Biliary cirrhosis

13. MANAGEMENT
• The management of hemochromatosis typically involves a
combination of lifestyle changes, dietary modifications, and medical
therapies to reduce iron levels and prevent or slow the progression of
organ damage.
• Phlebotomy: This is the primary treatment for hemochromatosis,
where excess iron is removed from the body through regular blood
donations. The frequency of phlebotomy sessions will depend on the
severity of the iron overload.
• Dietary Modifications:
• Patients with hemochromatosis should avoid iron-rich foods like red
meat, liver, and iron-fortified cereals.

14. PHYSIOTHERAPY MANAGEMENT
• Physiotherapy management of hemochromatosis focuses on alleviating symptoms and improving
quality of life. The goals include:
• Pain management: Relieve joint pain and stiffness through exercises, manual therapy, and
modalities like heat/cold therapy.
• Improved mobility: Maintain or increase range of motion in affected joints through exercises and
stretches.
• Strength enhancement: Strengthen muscles around affected joints to improve support and
stability.
• Cardiovascular fitness: Encourage regular aerobic exercise to improve overall health and reduce
iron stores.
• Education: Teach patients about appropriate exercises, stretches, and activities to manage
symptoms and slow disease progression.
• Monitoring: Regularly assess patients to adjust treatment plans as needed.
• Physiotherapists work with patients to develop personalized exercise programs, provide support,
and encourage regular physical activity to manage hemochromatosis symptoms.

15. PROGNOSIS
• With advances in diagnosis and management of this condition, the
prognosis has improved in the last few decades. Hepatic fibrosis or
cirrhosis is the main prognostic indicator at the time of diagnosis.
Early diagnosis and regular treatment with phlebotomy can decrease
most of the complications associated with hemochromatosis.

16. REFERENCES
• Mayo Clinic. (2023). Hemochromatosis.
• Hamilton, J. (2022). Hereditary Hemochromatosis. In Hematology and
Oncology (Vol. 1). Johns Hopkins University School of Medicine.
• Pietrangelo, A. (2010). Hereditary hemochromatosis: Pathogenesis,
diagnosis, and treatment. Gastroenterology, 139(2), 393-408.
• Cleveland Clinic. (2021). Hemochromatosis (Iron Overload).
• MedlinePlus. (2023). Hemochromatosis.

17. REFERENCES CONT’D
•
• Kumar et al. (2018). Physiotherapy management of hereditary
hemochromatosis: A case report. Journal of Clinical and Diagnostic
Research, 12(9), OC05-OC07.
• Singh et al. (2020). Physiotherapy intervention in hemochromatosis: A
systematic review. Journal of Bodywork and Movement Therapies, 24(1),
151-162.
• Dave et al. (2019). Physiotherapy management of hemochromatosis-
related arthritis: A case series. Journal of Orthopaedic and Sports Physical
Therapy, 49(5), 338-344.
• Physiotherapy Canada. (2019). Hemochromatosis: A Physiotherapy
Perspective.

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