Hemochromatosis

• Prevalence: the most frequent genetic disease in the

white population
• Age of onset: individuals > 40 years
• Symptoms start to show when body iron levels reach >
20 g.
• Before menopause, women lose iron via menstruation
and pregnancy, which slows down iron accumulation
within the body. As a result, symptom onset occurs
later in women (typically postmenopausal) than in
men.
Etiology
Primary (hereditary) hemochromatosis
• Classical and most frequent form: adult hemochromatosis type I
• Inheritance: autosomal recessive
Secondary iron overload (secondary hemochromatosis)
• Caused by iron overload
• Transfusion-related (e.g., in individuals with beta-thalassemia major
or other forms of chronic anemia requiring chronic transfusion)
• Ineffective erythropoiesis
a) Thalassemia
b) Sickle-cell anemia
Clinical Features
Liver
• Hepatomegaly
• Cirrhosis
• Increased risk of hepatocellular carcinoma
Pancreas: signs of diabetes mellitus
Skin: hyperpigmentation, bronze skin
Pituitary gland: hypogonadism, erectile dysfunction, testicular atrophy, loss of libido,
amenorrhea
Joints: arthralgia (typically symmetrical arthropathy of the MCP joints II and III);
(accumulation of calcium pyrophosphate)
Heart
• Cardiomyopathy due to cardiac siderosis
• Can lead to chamber remodeling and subsequent dilated (reversible); or restrictive
cardiomyopathy
• Cardiac arrhythmias
• Congestive heart failure
Skin Pigmentation
Investigation
 Laboratory studies
Diagnosis of iron overload
• ↑ Serum ferritin
• ↑ Transferrin saturation
• ↑ Serum iron
Genetic testing (HFE gene)
• Homozygous C282Y, homozygous H63D, or heterozygous
C282Y/H63D mutation in the HFE gene confirms the diagnosis.
Additional studies
• ↑ Hepatocellular enzymes (e.g., AST, ALT)
Liver biopsy
Management
 1.Approach
• Management is guided by a specialist (e.g., hepatologist,
gastroenterologist, or hematologist).
Hereditary hemochromatosis: Therapeutic phlebotomy and chelation
therapy are the primary options for iron removal.
Secondary iron overload
• Address the underlying cause (e.g., alcohol use disorder) to stop
iron loading.
• Consider iron removal on a case-by-case basis.
• Counseling and education: Early treatment can stabilize organ
damage, improve symptoms, and increase life expectancy.
 2.Main treatment
Therapeutic phlebotomy
• Indications
• First-line treatment for hereditary
hemochromatosis
Iron chelation therapy
• Chelating agents: deferoxamine, deferasirox,
or deferiprone
 Therapeutic phlebotomy
Indications
• First-line treatment for hereditary hemochromatosis
(including asymptomatic patients)
• Consider in patients with secondary iron overload (e.g., for
patients with symptomatic porphyria cutanea tarda)
Therapeutic regimen
• Initial phase: ∼ 500 mL of blood removed weekly over 1–2
sessions; serum ferritin goal of 50–100 ng/mL
• Maintenance phase: ∼ 500 mL of blood removed 3–4 times
per year; serum ferritin goal of ∼ 50 ng/mL
 Iron chelation therapy
Indications
• First-line treatment for secondary iron overload due to
iron-loading anemia
• Consider for hereditary hemochromatosis refractory to
therapeutic phlebotomy and patients with
contraindications to phlebotomy.
Chelating agents: deferoxamine, deferasirox, or deferiprone
Important considerations
• High cost Check renal function prior to
administration of chelating
• Significant risk of adverse effects agents because of the risk of
nephrotoxicity and renal
accumulation.
 Liver transplantation
Indications
• Decompensated cirrhosis
• Hepatocellular carcinoma
• Important consideration: Untreated iron
overload is not a contraindication to
transplantation.
 Additional therapies
Dietary changes
• Advise avoidance of iron and vitamin C supplements.
• Encourage strict avoidance of alcohol.
• No need to reduce dietary iron
Proton pump inhibitors (PPIs)
• Can decrease iron absorption
• Consider as an adjunct to phlebotomy.
• Only recommended for patients with an indication for PPIs (e.g., GERD)
Erythrocytapheresis
• Selective removal of red blood cells from the patient's circulation
• Useful for patients with thrombocytopenia or hypoproteinemia
 Patient counseling
• Early treatment of iron overload may:
• Improve fatigue and skin hyperpigmentation
• Reverse early organ damage (e.g., elevated liver
chemistries, early cardiomyopathy)
• Increase life expectancy
• It may be possible to prevent the progression of
advanced complications , but they cannot be
reversed.