Haemochromatosis is an inherited disorder characterised by excessive iron accumulation due to dysregulated iron absorption.
The most common form, hereditary haemochromatosis (HH), results from mutations in genes regulating hepcidin, the key hormone controlling iron homeostasis.
This leads to increased intestinal iron absorption and unregulated iron release from macrophages, causing progressive iron overload in multiple organs, including the liver, heart, pancreas, joints, and endocrine glands.
Aetiology
Genetic Basis
Haemochromatosis is an autosomal recessive disorder caused by mutations affecting iron metabolism, leading to excessive iron absorption.
The most common form, Type 1 hereditary haemochromatosis (HH), results from mutations in the HFE gene located on chromosome 6p21.3.
Homozygosity for the C282Y mutation is the predominant genetic variant associated with clinically significant iron overload, though not all carriers develop symptomatic disease.
The H63D variant is more common but typically does not cause iron overload unless present in combination with C282Y as a compound heterozygote.
The S65C variant is rare and generally considered to have little clinical significance in iron loading.
Other Genetic Forms
Type 2 (Juvenile Haemochromatosis):
Caused by mutations in HJV (HFE2) on chromosome 1q21 or HAMP on chromosome 19q13.
Leads to early-onset severe iron overload due to profound hepcidin deficiency, often manifesting before age 30.
Type 3 Haemochromatosis:
Results from mutations in TFR2 (transferrin receptor 2) on chromosome 7q22.
Produces a phenotype similar to HFE-related HH but with earlier onset and greater severity.
Type 4 Haemochromatosis (Ferroportin Disease):
The only autosomal dominant form, caused by mutations in SLC40A1 (ferroportin gene).
Unlike other forms, iron accumulates in macrophages rather than hepatocytes, leading to a distinct clinical presentation with milder systemic iron overload.
Phenotypic Expression and Risk Modifiers
Clinical expression varies significantly among individuals with HFE mutations, influenced by genetic and environmental factors.
Sex Differences: Males are at higher risk due to the absence of physiological iron loss from menstruation and pregnancy.
Iron Markers: High transferrin saturation and ferritin levels above 1000 ng/mL increase the likelihood of clinical disease.
Environmental Influences: Alcohol consumption, obesity, metabolic disorders (such as type 2 diabetes), and chronic infections like hepatitis can exacerbate iron accumulation and disease severity.
Mechanism of Iron Dysregulation
Mutations in HFE and other related genes impair the production or function of hepcidin, the primary regulator of iron absorption.
In HFE-associated haemochromatosis, defective hepcidin regulation causes continuous iron absorption despite sufficient body stores.
Mutations in HJV, HAMP, and TFR2 result in even more severe hepcidin deficiency, leading to aggressive iron overload at younger ages.
SLC40A1 mutations in ferroportin disease result in abnormal iron export from macrophages, leading to intracellular iron sequestration rather than systemic overload.
Pathophysiology
Iron Regulation and Hepcidin Dysfunction
The HFE gene plays a key role in iron homeostasis by regulating hepcidin, the primary iron-regulatory hormone.
In C282Y homozygotes, hepcidin levels are inappropriately low despite replete iron stores, leading to continuous iron absorption in the duodenum.
Reduced hepcidin allows excessive iron release from macrophages involved in erythrophagocytosis, contributing to elevated serum iron and transferrin saturation.
Iron Accumulation and Tissue Damage
Excess iron is deposited in multiple organs, including the liver, heart, pancreas, pituitary, and joints.
Iron overload leads to oxidative stress through the generation of free radicals, causing DNA damage, protein misfolding, and lipid peroxidation, which results in fibrosis and organ dysfunction.
Liver fibrosis occurs with significant iron accumulation, and in some cases, fibrosis can regress following iron removal.
Cardiac iron overload may lead to cardiomyopathy, heart failure, and arrhythmias, which may improve with iron depletion therapy.
Metabolic and Endocrine Impact
Pancreatic beta-cell dysfunction due to iron deposition is linked to diabetes mellitus, particularly in the presence of cirrhosis.
The relationship between iron overload and diabetes remains complex, with studies showing variable associations.
Pituitary iron accumulation can lead to hypogonadotropic hypogonadism, resulting in decreased libido, impotence, and amenorrhea.
Joint involvement due to iron deposition leads to arthropathy, which is often unresponsive to phlebotomy.
Classification of Haemochromatosis:
Type 1 (HFE-related haemochromatosis):
Autosomal recessive disorder caused by HFE mutations, primarily C282Y homozygosity.
Accounts for the majority of cases, with variable phenotypic expression.
Type 2 (Juvenile Haemochromatosis):
Results from mutations in HJV (HFE2) or HAMP, causing severe early-onset iron overload due to profound hepcidin deficiency.
Type 3 (Transferrin Receptor 2-related Haemochromatosis):
Caused by TFR2 mutations, leading to a phenotype similar to HFE-related haemochromatosis but with an earlier presentation.
Type 4 (Ferroportin Disease):
Autosomal dominant disorder caused by SLC40A1 mutations, leading to macrophage iron retention rather than systemic overload.
Alternative Classification by the BIOIRON Society
A newer classification includes:
HFE-related
Non-HFE-related
Digenic (involving mutations in two different iron metabolism genes)
Molecularly undefined haemochromatosis
Ferroportin disease is excluded from this classification due to its distinct phenotype.
Staging System for Disease Severity
Stage 0: Normal transferrin saturation and ferritin, asymptomatic.
Stage 1: Increased transferrin saturation (>45%) but normal ferritin, no symptoms.
Stage 2: Increased transferrin saturation and ferritin, but no symptoms.
Stage 3: Increased transferrin saturation and ferritin with symptoms such as fatigue, arthropathy, or impotence.
Stage 4: Increased transferrin saturation and ferritin with organ damage (e.g., cirrhosis, cardiomyopathy, insulin-dependent diabetes).
Epidemiology
Prevalence and Geographic Distribution
Haemochromatosis is one of the most common genetic disorders in individuals of European ancestry, with a gene frequency of approximately 4–6%.
The prevalence of HFE-related haemochromatosis is similar across the US, Europe, and Australia, with an estimated 1 case per 200 to 400 individuals.
The major HFE mutation (C282Y) is common in White populations, with approximately 1 in 10 individuals carrying one copy and about 1 in 200 being homozygous.
The highest prevalence of C282Y homozygosity has been reported in Ireland, where it affects 1 in 83 people.
The mutation is significantly less common in Hispanic (0.27 per 1000), Pacific Islander (0.12 per 1000), and Black populations (0.14 per 1000).
HFE-related haemochromatosis is rare in East Asian populations, where iron overload is more often associated with mutations in HJV, HAMP, TFR2, or SLC40A1.
Genetic Distribution and Population Risk
C282Y homozygotes account for 82–90% of clinical diagnoses in individuals of Northern European descent.
Compound heterozygotes (C282Y/H63D) have a lower risk of iron overload, though some individuals develop clinical disease.
Homozygosity for H63D is rare and is not generally associated with significant iron overload.
Sex Differences in Disease Expression
Men are affected approximately 2–3 times more often than women, with a male-to-female ratio of 1.8:1 to 3:1.
Women typically develop symptoms later due to physiological iron loss from menstruation and pregnancy, which delays iron accumulation.
In a study of individuals of Northern European descent, iron overload-related disease was found in 28% of C282Y homozygous men and only 1.2% of C282Y homozygous women.
Among individuals with untreated hereditary haemochromatosis, severe liver disease is seen in about 1 in 10 men, while the risk is significantly lower in women.
Age of Onset and Clinical Progression
Haemochromatosis symptoms typically become apparent after age 40 in men and after menopause in women.
Juvenile haemochromatosis, caused by mutations in HJV or HAMP, presents at a much younger age (10–30 years).
Neonatal iron overload, which is unrelated to HFE mutations, is a distinct entity with rapid progression to liver failure.
Ethnic and Racial Variations
HFE-related haemochromatosis is most common in individuals of Celtic, Scandinavian, and Northern European ancestry.
In Mediterranean populations, non-HFE forms of haemochromatosis are more prevalent, particularly mutations in TFR2 and SLC40A1.
The G320V mutation has been found among juvenile haemochromatosis patients in Central Europe and Greece, making genetic screening useful in these regions.
History
Typical Presentation
Many individuals with hereditary haemochromatosis (HH) are asymptomatic at the time of diagnosis, often detected through incidental findings of elevated iron studies or family screening.
When symptoms develop, they typically emerge between ages 30 and 50 in men, and later in women due to iron loss through menstruation and pregnancy.
Juvenile haemochromatosis, associated with HJV or HAMP mutations, presents earlier, often before age 30, with severe iron overload.
Common Early Symptoms
Fatigue (most frequently reported symptom).
Joint pain (arthralgia), particularly in the hands.
Erectile dysfunction in men.
Decreased libido in both men and women.
Unexplained weakness or lethargy.
Risk Factors
Genetic Factors:
Homozygosity for the C282Y mutation in the HFE gene is the strongest risk factor.
Compound heterozygosity (C282Y/H63D) has a lower risk but may lead to clinical iron overload.
Other rare mutations (HJV, HAMP, TFR2, SLC40A1) contribute to non-HFE haemochromatosis.
Sex:
Men are more likely to develop iron overload-related complications due to lack of menstrual iron loss.
Women often present after menopause when iron accumulation accelerates.
Age:
Symptoms usually develop in mid-adulthood after decades of progressive iron accumulation.
Family History:
A family history of haemochromatosis or iron overload disorders increases the likelihood of disease.
Dietary and Lifestyle Factors:
High dietary iron intake may exacerbate iron accumulation.
Alcohol consumption is a significant risk factor for hepatic complications in HH.
Hepatomegaly (liver enlargement) is present in up to 95% of symptomatic patients.
Progressive iron deposition leads to cirrhosis, which is the most common cause of death in HH patients.
Symptoms of liver dysfunction include abdominal pain, jaundice, and signs of portal hypertension (ascites, varices).
Endocrine and Metabolic Symptoms
Diabetes mellitus occurs due to iron accumulation in pancreatic beta cells, leading to insulin deficiency.
Hypogonadism, particularly in men, results from pituitary iron deposition, causing impotence, infertility, and decreased libido.
Amenorrhea is less common but can occur in female patients.
Cardiac Symptoms
Dilated cardiomyopathy, arrhythmias, and heart failure may occur due to cardiac iron overload.
Symptoms include palpitations, shortness of breath, and lower extremity oedema.
Skin Changes
Skin bronzing or hyperpigmentation results from iron deposition and increased melanin production.
Darkening often starts on sun-exposed areas, hands, and in old scars.
Musculoskeletal Symptoms
Joint pain, particularly affecting the second and third metacarpophalangeal (MCP) joints.
Chondrocalcinosis (calcium pyrophosphate deposition) in large joints like the knees and wrists.
Symptoms often persist even after iron removal therapy.
Other General Symptoms
Chronic fatigue, apathy, and generalised weakness.
Hair thinning and koilonychia (spoon-shaped nails).
Osteopenia and osteoporosis, particularly in patients with concurrent hypogonadism.
Examination
General Physical Signs
Fatigue, Weakness, Lethargy: Common but nonspecific symptoms. Patients may appear generally fatigued or report chronic tiredness.
Cutaneous Manifestations
Skin Pigmentation: Hyperpigmentation or bronzing, particularly on sun-exposed areas, extensor surfaces, dorsum of the hands, and in old scars. Over time, skin may progress from bronze to a slate-grey color.
Koilonychia: Spoon-shaped nails, typically affecting the thumb, index, and middle fingers, observed in up to 50% of patients.
Musculoskeletal Findings
Arthropathy: Joint pain and stiffness, particularly in the second and third metacarpophalangeal (MCP) joints and proximal interphalangeal (PIP) joints.
Radiographic Changes: Hand X-rays may reveal squared-off bone ends, hook-like osteophytes, joint space narrowing, sclerosis, chondrocalcinosis (calcification in cartilage), and cyst formation.
Chondrocalcinosis: Often affects larger joints like knees and wrists, potentially asymptomatic but visible on imaging.
Hepatic Signs
Hepatomegaly: Detected in 10% to 30% of patients, often associated with cirrhosis. On palpation, liver may be enlarged and tender.
Signs of Chronic Liver Disease: Palmar erythema, spider angiomas, jaundice, or signs of liver failure such as ascites and encephalopathy.
Endocrine and Reproductive Findings
Impotence and Loss of Libido: Common in males, associated with hypogonadism due to pituitary iron deposition.
Amenorrhea: May occur in women, particularly in advanced disease.
Hypogonadism: Decreased secondary sexual characteristics in men, such as reduced body hair and gynecomastia.
Cardiac Findings
Cardiomyopathy: May present with signs of heart failure, including peripheral oedema, jugular venous distension, and S3/S4 heart sounds.
Arrhythmias: Atrial fibrillation or sick sinus syndrome due to iron deposition in cardiac tissues.
Metabolic and Endocrine Symptoms
Diabetes Mellitus: Signs of diabetes such as polyuria, polydipsia, and glycosuria may be present, often indicating pancreatic involvement.
Thyroid Dysfunction: Symptoms of hypothyroidism or hyperthyroidism may be evident.
Other Systemic Signs
Osteopenia/Osteoporosis: Particularly in those with concurrent hypogonadism or long-standing disease.\
Hair Loss: Partial or total body hair loss, most commonly in the pubic region, observed in about 60% of patients.
Investigations
First-Line Investigations
Serum Transferrin Saturation:
The first laboratory test to become abnormal in haemochromatosis.
Persistent transferrin saturation >50% in men and >45% in women is suggestive of iron overload.
There is significant biological variability in transferrin saturation, which is not eliminated by fasting. If initial values are normal but suspicion remains high, repeat testing is recommended.
Serum Ferritin:
Used to estimate the degree of iron overload but is also an acute-phase reactant.
Elevated levels may indicate haemochromatosis but can also occur due to inflammation, alcohol use, chronic viral hepatitis, non-alcoholic fatty liver disease, and metabolic syndrome.
Levels >300 ng/mL in men and >200 ng/mL in women warrant further investigation.
The risk of severe complications increases with ferritin >1000 ng/mL.
Genetic Testing
HFE Mutation Analysis:
C282Y homozygosity is the most common genetic abnormality associated with haemochromatosis, particularly in individuals of Northern European descent.
C282Y/H63D compound heterozygosity may cause a milder phenotype, particularly when combined with other acquired risk factors.
H63D homozygosity is rarely associated with significant iron overload.
Genetic testing should be performed in individuals of European descent with biochemical evidence of iron overload.
Iron Storage Assessment:
MRI Liver:
A non-invasive method to measure liver iron concentration with high sensitivity and specificity.
Liver-to-muscle signal intensity ratio <0.88 suggests iron overload.
Liver Biopsy:
Previously the gold standard for diagnosing iron overload, now reserved for evaluating fibrosis and cirrhosis.
Can assess hepatic iron content and differentiate between primary haemochromatosis and secondary causes of iron overload.
Assessment of Organ Involvement:
Liver Function Tests (LFTs):
Transaminases may be mildly elevated, usually not exceeding twice the upper normal limit.
Characterised by chondrocalcinosis and joint pain, similar to haemochromatosis arthropathy.
Unlike haemochromatosis, it is not associated with systemic iron overload.
Rheumatoid Arthritis:
Chronic inflammatory arthritis that can cause joint destruction.
Unlike haemochromatosis, it is typically associated with positive rheumatoid factor and anti-CCP antibodies.
Other Causes of Hyperferritinemia
Hereditary Hyperferritinemia-Cataract Syndrome:
A rare autosomal dominant condition caused by mutations in the FTL gene.
Unlike haemochromatosis, serum iron and transferrin saturation remain normal.
Ferroportin Disease:
Caused by mutations in SLC40A1, leading to iron sequestration in macrophages.
Unlike haemochromatosis, iron accumulates in reticuloendothelial cells rather than parenchymal organs.
Aceruloplasminemia:
A rare disorder with iron accumulation in the liver, brain, and pancreas due to defective iron export.
Unlike haemochromatosis, transferrin saturation is low, and serum ceruloplasmin is undetectable.
Gaucher Disease:
A lysosomal storage disorder that can present with hepatosplenomegaly and hyperferritinemia.
Unlike haemochromatosis, iron overload is not the primary pathological feature.
Management
General Approach
The primary goal of management is to prevent iron overload-related complications by depleting excess iron stores and maintaining optimal iron levels.
In asymptomatic individuals with mild iron elevation (serum ferritin <1000 ng/mL), monitoring may be an option, as progression is slow in some patients.
Regular surveillance with serum ferritin measurement is recommended for those with minimal iron overload and no organ damage.
Lifestyle Modifications
Dietary Recommendations:
Patients should follow a balanced diet while avoiding iron-fortified foods and iron supplements.
Vitamin C supplements should be avoided as they enhance iron absorption. However, in cases of parenteral iron chelation, small doses may help increase iron availability for chelation.
Alcohol consumption should be limited or completely avoided in the presence of liver disease, as it exacerbates iron accumulation.
Raw or undercooked shellfish and seawater exposure should be avoided due to increased susceptibility to Vibrio vulnificus infections.
Vaccinations:
Hepatitis A and B vaccination should be considered in patients at risk of exposure, as chronic viral hepatitis worsens liver damage in haemochromatosis.
Phlebotomy (First-Line Therapy for Iron Reduction)
Induction Phase:
Weekly or biweekly phlebotomy of 500 mL per session.
The aim is to achieve a target serum ferritin of 50–100 ng/mL.
Hemoglobin should be monitored to avoid anemia; phlebotomy should be deferred if hemoglobin falls below 11 g/dL.
Serum ferritin should be checked every 10–12 phlebotomy sessions, with more frequent monitoring as levels approach the target range.
Maintenance Phase:
Typically requires 2–6 sessions per year, depending on individual iron accumulation.
Patients with well-controlled iron levels may become eligible blood donors.
A low-iron diet can reduce annual phlebotomy requirements by 0.5 to 1.5 liters.
Alternative Iron Reduction Therapies
Erythrocytapheresis:
A red blood cell removal procedure that may be more efficient than phlebotomy, requiring fewer sessions.
Associated with fewer hemodynamic side effects, but mild citrate reactions are common.
Proton Pump Inhibitors (PPIs):
By increasing gastric pH, PPIs reduce non-heme iron absorption, potentially decreasing the frequency of phlebotomy sessions.
Used as adjunctive therapy but not a replacement for phlebotomy.
Iron Chelation Therapy (For Patients Who Cannot Undergo Phlebotomy)
Indications:
Reserved for patients with contraindications to phlebotomy, such as severe anemia, cardiac disease, or poor venous access.
Used in severe juvenile haemochromatosis or patients with advanced iron overload.
Chelation Agents:
Deferasirox: Oral iron chelator, effective in reducing liver iron stores. Not recommended in advanced liver disease due to potential nephrotoxicity and gastrointestinal side effects.
Deferoxamine: Parenteral iron chelator used for patients unable to tolerate oral therapy.
Deferiprone: Oral chelator, effective in removing cardiac iron, but associated with agranulocytosis and gastrointestinal intolerance.
Vision and hearing assessments should be performed at least annually for patients on chelation therapy.
Liver Disease Management
Screening for Fibrosis and Cirrhosis:
All patients with haemochromatosis should be assessed for liver fibrosis at diagnosis.
Non-invasive markers such as transient elastography (FibroScan) or serum fibrosis scores (APRI, FIB-4) may be used.
Liver biopsy is now reserved for patients with ferritin >1000 ng/mL or abnormal liver enzymes.
Surveillance for Hepatocellular Carcinoma (HCC):
Patients with cirrhosis should undergo ultrasound and alpha-fetoprotein (AFP) measurement every six months to screen for HCC.
Cardiac and Endocrine Monitoring
Echocardiogram and MRI Heart:
Recommended in patients with suspected cardiac involvement or juvenile haemochromatosis.
Cardiac dysfunction may improve with iron reduction therapy.
Endocrine Assessment:
Testosterone, FSH, and LH levels should be checked in males with symptoms of hypogonadism.
Bone densitometry (DEXA scan) is indicated for patients at risk of osteoporosis.
Management of Non-C282Y Homozygous Patients
Patients with C282Y/H63D Compound Heterozygosity:
Managed based on their iron status and the presence of additional risk factors.
If iron overload is present, phlebotomy may be considered, but individualised assessment is required.
Other Genetic Variants:
Patients with rare mutations in HJV, HAMP, TFR2, or SLC40A1 require specialised evaluation.
Long-Term Monitoring
Patients with Controlled Iron Levels:
Routine monitoring every 6–12 months with serum ferritin and transferrin saturation.
Regular assessment for potential complications, including liver disease, diabetes, and cardiac dysfunction.
Patients with Ongoing Iron Accumulation:
Require continued phlebotomy or alternative therapies based on clinical status.
Prognosis
Factors Influencing Prognosis
The prognosis in haemochromatosis depends on the degree and duration of iron overload, as well as early detection and treatment.
Not all individuals with HFE mutations develop progressive iron loading or clinical disease, with some remaining asymptomatic throughout life.
In a large screening study of approximately 65,000 individuals, the absolute risk of liver damage was 5% in C282Y homozygous men and <1% in women.
Early identification and initiation of treatment with phlebotomy can ensure a normal life expectancy.
Impact of Cirrhosis on Survival
The presence of cirrhosis at diagnosis is the most critical prognostic factor.
Patients without significant hepatic fibrosis have a normal life expectancy with appropriate iron reduction therapy.
In contrast, those with cirrhosis have an increased risk of liver-related complications and a reduced lifespan.
In one study, individuals with haemochromatosis and cirrhosis had a significantly higher risk of hepatocellular carcinoma (HCC), with an odds ratio of 11 compared to the general population.
Liver-related mortality is highest in those with serum ferritin >2000 ng/mL at diagnosis.
Mortality and Complications
If untreated, haemochromatosis can lead to severe organ damage and premature death due to complications such as:
Increased risk of infections, including Vibrio vulnificus sepsis
In one study, 55% of untreated patients with advanced haemochromatosis died from liver failure or cirrhosis-related complications.
Cancer and Other Disease Associations
C282Y homozygosity has been linked to increased risks of colorectal cancer, breast cancer, and pneumonia.
Men are affected more than women, with haemochromatosis-related complications observed in up to 40% of men and 13% of women.
There is an ongoing debate regarding whether heterozygosity (C282Y/H63D) is associated with a shortened lifespan, with some studies suggesting an age-related reduction in HFE mutation carriers.
Post-Liver Transplantation Survival
Haemochromatosis patients who undergo liver transplantation have lower survival rates compared to those transplanted for other indications.
One-year survival is approximately 58%, and five-year survival is 42%, with most deaths occurring due to infections or cardiac complications.
Sepsis is the leading cause of early post-transplant mortality, while heart failure accounts for most late deaths.
Long-Term Monitoring and Prevention
Regular follow-up is essential for patients with haemochromatosis, particularly those with liver fibrosis or cirrhosis.
Screening for hepatocellular carcinoma (HCC) with ultrasound and alpha-fetoprotein (AFP) every six months is recommended for patients with cirrhosis.
Phlebotomy therapy significantly improves outcomes and can prevent most complications if initiated early.
Complications
Liver-Related Complications
Cirrhosis:
Progressive iron deposition in the liver leads to fibrosis and cirrhosis, particularly in those with additional risk factors like alcohol use or viral hepatitis.
Once cirrhosis develops, the risk of hepatocellular carcinoma (HCC) increases significantly.
Liver transplantation is considered in end-stage liver disease, with reported one-year survival of 88.7% and five-year survival of 77.5%.
Hepatocellular Carcinoma (HCC):
A major cause of mortality in haemochromatosis patients with cirrhosis.
Rare cases of HCC have been reported in haemochromatosis patients without cirrhosis and even after iron depletion therapy.
Surveillance with liver ultrasound every six months is recommended for cirrhotic patients.
Metabolic and Endocrine Complications
Diabetes Mellitus:
Iron accumulation in pancreatic beta cells leads to insulin deficiency and diabetes mellitus.
The risk of diabetes is significantly higher in patients with both haemochromatosis and cirrhosis.
Phlebotomy does not always improve glycemic control, and HbA1c levels may overestimate glycemic status in patients undergoing frequent phlebotomy.
Hypogonadism:
The second most common endocrine disorder associated with haemochromatosis after diabetes.
Results from iron deposition in the pituitary gland, leading to reduced gonadotropin secretion.
Symptoms include decreased libido, erectile dysfunction, and testicular atrophy.
Cardiac Complications
Chronic Congestive Heart Failure:
Iron deposition in the myocardium can lead to dilated cardiomyopathy and heart failure.
Patients may present with fluid overload, fatigue, and arrhythmias.
Iron removal therapy can reverse early cardiac dysfunction, but advanced heart failure may be irreversible.
Arrhythmias and Conduction Abnormalities:
Iron toxicity can disrupt cardiac electrical conduction, leading to atrial fibrillation, sick sinus syndrome, or other arrhythmias.
Patients presenting with heart failure or arrhythmias should undergo aggressive iron-lowering treatments.
Skeletal Complications
Osteoporosis and Bone Loss:
Increased bone resorption has been observed in haemochromatosis, independent of hypogonadism or cirrhosis.
Patients are at higher risk of fractures, and bone densitometry (DEXA scan) is recommended for monitoring.
Infections
Patients with iron overload are at increased risk of infection due to the enhanced growth of iron-dependent bacteria.
Common pathogens include:
Vibrio vulnificus (from raw seafood or seawater exposure)
Listeria monocytogenes
Yersinia enterocolitica
Avoidance of raw or undercooked seafood is strongly advised.
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