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PRYSTACKA-SZAR, Dominika, RULEWSKA, Natalia, GRABOWSKI, Filip, SIEMKO, Jakub, NESKA, Dagmara, STADLER-
SZAJDA, Justyna, CZYŻNIKIEWICZ, Adrianna, STOŁOWSKI, Wenancjusz, BUJAK, Magdalena and
WAŚNIOWSKA, Magdalena. Hereditary hemochromatosis: pathogenesis, symptoms, diagnosis and current treatment - literature
review. Journal of Education, Health and Sport. 2025;80:58359 eISSN 2391-8306.
https://doi.org/10.12775/JEHS.2025.80.58359
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Received: 29.01.2025. Revised: 28.02.2025. Accepted: 22.03.2025. Published: 10.04.2025.
1
Hereditary hemochromatosis: pathogenesis, symptoms, diagnosis and current treatment
- literature review
Dominika Prystacka-Szar
Ludwik Rydygier Memorial Specialized Hospital in Krakow
https://orcid.org/0009-0003-6533-4247
Natalia Rulewska
Provincial Specialist Hospital in Ciechanów St. Powstańców Wielkopolskich 2, 06-400
Ciechanów, Poland
https://orcid.org/0009-0008-4515-7403
Filip Grabowski
Provincial Specialist Hospital in Ciechanów St. Powstańców Wielkopolskich 2, 06-400
Ciechanów, Poland
https://orcid.org/0009-0007-0466-2764
2
Jakub Siemko
Ludwika Błażka Provincial Multi-Specialist Hospital in Inowrocław St. Poznańska 97, 88-100
Inowrocław
https://orcid.org/0009-0009-9318-9458
Dagmara Neska
Ludwika Błażka Provincial Multi-Specialist Hospital in Inowrocław St. Poznańska 97, 88-100
Inowrocław,PL
https://orcid.org/0009-0003-1900-954X
Justyna Stadler-Szajda
Ludwika Błażka Provincial Multi-Specialist Hospital in Inowrocław St. Poznańska 97, 88-100
Inowrocław
https://orcid.org/0000-0002-1742-1835
Adrianna Czyżnikiewicz
Ludwika Błażka Provincial Multi-Specialist Hospital in Inowrocław St. Poznańska 97, 88-100
Inowrocław
https://orcid.org/0009-0007-4541-7175
Wenancjusz Stołowski
Ludwika Błażka Provincial Multi-Specialist Hospital in Inowrocław St. Poznańska 97, 88-100
Inowrocław
https://orcid.org/0009-0009-0317-1212
Magdalena Bujak
Krakow University Hospital St. Macieja Jakubowskiego 2, 30-688 Krakow
https://orcid.org/0009-0008-9274-3595
Magdalena Waśniowska
Stefana Żeromskiego Specialist Hospital in Kraków Os. Na Skarpie 66, 31-913 Kraków
https://orcid.org/0009-0006-0614-8307
3
ABSTRACT
Introduction:
Hereditary hemochromatosis is the most common genetic disorder in Northern Europe. It
involves an overload of iron in the tissues due to a deficiency of the protein hepcidin. 85-90%
of cases are associated with homozygous mutations of the C282Y gene in the HFE gene.
Symptoms are nonspecific and include cardiac disorders, liver cirrhosis, hepatocellular
carcinoma, diabetes, hypogonadism and sexual dysfunction, and arthritis. The diagnosis of the
disease is based on demonstrating elevated serum ferritin levels and transferrin saturation, as
well as identifying the mutation responsible for hereditary hemochromatosis. Early diagnosis
is crucial in preventing permanent organ complications. Treatment methods include
phlebotomy, therapeutic erythrocytophoresis, and the use of iron chelating drugs. Early
detected and properly treated hemochromatosis allows for a lifespan comparable to the general
population.
Aim:
The purpose of this article is to provide a comprehensive summary of the etiology, symptoms,
diagnosis and treatment of hereditary hemochromatosis with an emphasis on the importance of
early detection and treatment of the disease.
Review methods:
A thorough analysis of several dozen research studies from recent years on hereditary
hemochromatosis and its complications was conducted. Studies available in PUBMED were
reviewed, the following keywords were used to search for sources: hemochromatosis; iron;
hepcidin; phlebotomy; deferoxamine; therapeutic erythrocytapheresis.
Conclusion:
Hereditary hemochromatosis is a disease that in most patients runs a covert course. If
unrecognized and untreated, it carries many life-threatening complications.
Our work highlights the consequences of excess iron in the body and demonstrates how early
detection and appropriate treatment of hemochromatosis can result in a life expectancy
comparable to that of the general population.
Keywords: hemochromatosis; iron; hepcidin; phlebotomy; deferoxamine; therapeutic
erythrocytapheresis
4
Introduction
Hereditary hemochromatosis (HH) is the most common genetic disorder in Northern
Europe, affecting even 1:200-1:400 individuals. It occurs significantly more often in men.
There are four main types of hereditary hemochromatosis (tab. 2). 85-90% of cases involve
homozygous mutations of C282Y and heterozygous mutations of C282Y/H63D in the HFE
gene on chromosome 6 (chromosome 6p21.3). (1) Types 1, 2, and 3 of hereditary
hemochromatosis are inherited in an autosomal recessive manner, while type 4 is autosomal
dominant.
In hereditary hemochromatosis, there is an overload of iron in the tissues due to a
deficiency of the protein hepcidin - the primary regulator of iron metabolism. The diagnosis is
most often made between the ages of 40-50, earlier in males than in females. In females, a
physiological regulator of iron levels is monthly menstruation.
Symptoms of hemochromatosis are nonspecific and occur only in about 10% of patients
with a homozygous mutation (2). Symptoms include liver cirrhosis, hepatocellular carcinoma,
joint pain, sexual disorders including impotence, cardiomyopathy, cardiac rhythm disorders,
endocrinopathies such as diabetes, hypogonadism, and hypopituitarism. The most characteristic
finding in laboratory studies is elevated ferritin concentration - the iron store in the body, and
increased transferrin saturation (3). Genetic testing is the gold standard for diagnosing HH.
Materials and methods
A thorough analysis of several dozen research studies from recent years on hereditary
hemochromatosis and its complications was conducted. Studies available in PUBMED were
reviewed, the following keywords were used to search for sources: hemochromatosis; iron;
hepcidin; phlebotomy; deferoxamine; therapeutic erythrocytapheresis.
Iron Metabolism
Iron is a chemical element essential to life. The daily iron requirement of the human
body is 0.5-3.0 mg. The daily loss of iron is about 1 mg, occurring through the shedding of
epithelium and epidermis, and in women, additionally through menstrual bleeding. Iron is
primarily absorbed in the duodenum and the initial section of the small intestine. Only 10% of
the dietary iron is absorbed, and 90% is excreted with feces. Iron can bind with apoferritin to
5
form ferritin or be transported with a protein carrier - ferroportin - to the extracellular fluid,
where it binds with transferrin and as a complex is distributed to the liver or bone marrow. Iron
is involved in many biochemical pathways, including hormone synthesis, deoxyribonucleic
acid (DNA) synthesis, and is a component of proteins - including hemoglobin, myoglobin -
responsible for oxygen transport. Iron plays a crucial role in erythropoiesis, in immunological
reactions, and in DNA replication and repair. The total body pool is 3-4 g - about 70% occurs
in the form of hemoglobin, and about 20% is stored as ferritin. (4, 5, 6, 7)
Ferritin is a protein whose main role is to store iron - it can store up to 4,500 atoms of
iron. It also serves as an acute-phase protein, with its levels increasing in inflammatory
conditions, autoimmune diseases, liver diseases, and malignant tumors. (7, 8, 9, 10)
Ferritin possesses ferroxidase activity - it converts Fe2+ to Fe3+, which it stores. The ferritin
molecule consists of the protein apoferritin and a core containing iron ions. It is composed of
24 subunits of two types - heavy (FTH) and light (FTL) ferritin chains. Tissues that store iron,
such as the liver/spleen, contain ferritin primarily composed of light chains, which have a more
stable structure and can store more iron than heavy chains. In contrast, tissues with high iron
oxidation activity, such as the heart/brain, contain ferritin primarily composed of heavy chains,
which have significant antioxidant activity. Ferritin is synthesized in response to high levels of
iron, whereas when the demand for iron increases, ferritin undergoes degradation. (11)
Transferrin is a protein produced by the liver, whose main task is to participate in the
transport of iron. Transferrin also serves a protective function - it binds free, toxic forms of iron,
thereby limiting its chemical activity and preventing the formation of free radicals. Transferrin
saturation (TSAT) determines how much iron is bound to transferrin and is calculated as the
ratio of serum iron to total iron-binding capacity (TIBC) x 100%. The normal range for TSAT
varies from 20-45% and is elevated in HH. (6, 12, 13)
The concentration of iron is primarily regulated by hepcidin - a system-wide regulator
of iron homeostasis. Hepcidin is a protein secreted by the liver, encoded by the HAMP gene,
whose main task is to maintain iron homeostasis in the body by regulating iron absorption in
the small intestine, regulating iron levels in the plasma, and distributing iron in tissues. Hepcidin
secretion depends on the level of iron in tissues, inflammatory states, and erythropoiesis. (7, 14)
An increase in iron concentration signals the release of hepcidin. Hepcidin is then secreted into
the bloodstream. Hepcidin binds to the cellular iron exporter, ferroportin. Ferroportin binds
6
divalent iron and transports it across the cell membrane into the circulation, where it is oxidized
by iron oxidase - hephaestin (HFE) - to the trivalent iron form (Fe3+) that binds to transferrin.
Binding of hepcidin to ferroportin causes internalization and degradation of both proteins.
Hence, hepcidin is a direct inhibitor of ferroportin. Hepcidin inhibits iron absorption from the
gastrointestinal tract and inhibits its release from macrophages - resulting in reduced serum iron
concentration. Under conditions of iron deficiency, there is a decrease in hepcidin secretion by
hepatocytes. This prevents degradation of ferroportin and allows the release of iron into the
bloodstream, simultaneously increasing iron absorption in the gastrointestinal tract - a process
handled by enterocytes of the duodenal villi.
Like ferritin, hepcidin is an acute-phase protein - in acute inflammatory states or chronic
diseases, its concentration increases. Reduced hepcidin levels occur in conditions of iron
overload such as HH, in thalassemias, dyserythropoietic anemias, and in states of iron
deficiency. (7, 14)
Maintaining proper iron levels is crucial, as both deficiency and excess of this element
are undesirable. Iron deficiency results in anemia, pica eating disorder (consumption of non-
edible substances such as chalk), delayed psychological development, and weakened immune
system response. Excess iron can also be toxic - unbound divalent iron participates in the Fenton
reaction. This results in the formation of highly reactive hydroxyl free radicals, followed by 8-
oxo-2’-deoxyguanosine, which causes damage to lipids, proteins, and DNA mutations leading
to the process of carcinogenesis. (15)
Diagnosis
The first and very characteristic biochemical indicator of iron tissue overload is an
elevated transferrin saturation (TSAT >45%). An increase in TSAT can precede an increase in
ferritin by several years. (13) In hereditary hemochromatosis, the TSAT level exceeds 45%,
while the ferritin levels in females exceed 200 ng/ml, and in males and postmenopausal women
exceed 300 ng/ml. These are not specific markers for hemochromatosis, as their elevated values
also occur in many other disease entities. (tab.1)
7
tab. 1 Laboratory Tests Used in the Diagnosis of Hereditary Hemochromatosis (16, 17)
Diagnostic
test
Criteria for hereditary
hemochromatosis
Differentiation
Ferritin
>200 ng/ml in females
>300 ng/ml in males
1. Hereditary Hemochromatosis
2. Still's Disease
3. Macrophage Activation Syndrome
4. Hemophagocytic Lymphohistiocytosis
(HLH)
5. Acute Phase Reaction
6. Chronic Kidney Disease (CKD)
7. Alcoholic Hepatitis
8. Chronic Viral Hepatitis Type B and C
9. Excessive Iron Supplementation
10. Multiple Blood Transfusions Due to
Chronic Anemia
Transferrin
Saturation
>45%
1. Hereditary Hemochromatosis
2. Sideroblastic Anemia
3. Excessive Iron Supplementation
4. Chronic Liver Diseases
The gold standard for detecting HH (Hereditary Hemochromatosis) is genetic testing.
80-90% of patients with clinically symptomatic HH are homozygous for the p.C282Y variant
in the HFE gene. Detecting homozygous C282Y mutations, along with elevated serum ferritin
levels and increased transferrin saturation, is sufficient for diagnosing HH. (18) In patients with
symptoms of iron overload and proven iron overload, such as increased iron stores in the liver
shown in biopsy or MRI, and a negative test for p.C282Y homozygosity, it is advisable to
conduct genetic tests for other genetic variants associated with HH. (tab.2) (18)
Features of iron overload and a negative HFE mutation for a young person, especially
before the age of 30, may indicate the presence of juvenile hemochromatosis (JH). This is a
very rare form of hemochromatosis - affecting only about 1 in 4.8 million people - females and
males equally. Juvenile hemochromatosis, depending on the subtype, is caused by mutations in
the HJV gene on chromosome 1q21 (subtype 2A) or in the HAMP gene on chromosome
8
19q31.1 (subtype 2B). Only a few cases of type 2B HH have been recorded. The most common
symptoms of JH are hypogonadism and cardiomyopathy. (19, 20, 21, 22)
Table 2. Types of hereditary hemochromatosis (2)
Type
Gene
Inheritance
1A (homozygous)
HFE - mutation C282Y
AR
1B (heterozygote)
HFE - mutation C282Y, H63D
AR
1C
HFE - mutation S65C
AR
2A (juvenile
hemochromatosis)
HJV
AR
2B (juvenile
hemochromatosis)
HAMP
AR
3HH
TFR2 (transferrin receptor 2)
AR
4A
SLC40A1
AD
4B
SLC40A1
AD
Ferritin levels above 1000 ng/ml are associated with higher mortality and a more
frequent occurrence of liver cirrhosis and hepatocellular carcinoma (HCC) (23) and are an
indication for performing a liver biopsy. (13)
Liver elastography (FibroScan) is a useful tool in the diagnosis and detection of
complications of HH. It is a non-invasive test that detects liver fibrosis. (13)
In a study conducted by Legros et al., it was shown that elastography has an 86% sensitivity
and 91% specificity in detecting liver fibrosis. Despite this, liver biopsy remains the gold
standard for assessing liver fibrosis. (24)
9
Symptoms and Complications of Hereditary Hemochromatosis
The classic triad of HH symptoms - diabetes, liver cirrhosis, and skin hyperpigmentation
- currently occurs in only 10% of patients. (25)
Most cases of HH are diagnosed due to abnormal laboratory results (elevated ferritin
levels) or the occurrence of hemochromatosis in family members. (26)
Symptoms of hereditary hemochromatosis include skin hyperpigmentation, hepatomegaly,
liver cirrhosis, hepatocellular carcinoma, cardiac complications such as restrictive and dilated
cardiomyopathy, cardiac arrhythmias, endocrinological complications including pituitary
hypofunction, hypogonadism, diabetes, and arthritis. (13, 27)
1. Heart:
In 10-15% of patients with hereditary hemochromatosis, the main symptoms of the disease
are cardiac. The most common cardiac complications are restrictive cardiomyopathy and dilated
cardiomyopathy. These complications have a progressive course, and in severe cases, they can
lead to death. The risk of developing cardiomyopathy is 306 times greater in patients with HH
than in the general population. (28)
Restrictive cardiomyopathy (RCM) is characterized by increased stiffness of the heart
muscle, resulting in abnormal filling of the chambers and progressive diastolic heart failure.
Systolic function is usually preserved in the early stages. As the disease progresses, systolic
dysfunction of both ventricles occurs, sometimes with rapid progression to acute heart failure.
RCM can cause symptoms of failure of both the left and right ventricles. (29) In
echocardiographic examination, characteristic features include enlargement of the walls of both
atria with relatively small ventricles and diastolic dysfunction of the left ventricle and high
filling pressures. Chronically elevated LV diastolic pressure induces pulmonary hypertension,
which tends to exacerbate right ventricular failure. Atrial enlargement and remodeling can lead
to atrial fibrillation. (30)
For dilated cardiomyopathy (DCM), characteristic features include enlargement of the heart
chambers - particularly significant is the dilation of the left ventricle with a reduction in ejection
fraction and a decrease in the thickness of the heart chamber walls. (31) Symptoms of DCM
result from progressive systolic heart failure. Detection of DCM is possible through an
echocardiogram, with the diagnostic criteria being LV end-diastolic volumes or diameters >2
standard deviations from normal and an ejection fraction <50%. (32) The definitive diagnosis
of cardiomyopathy is made based on a heart muscle biopsy. (6)
10
A common cardiac symptom in HH is arrhythmias caused by the deposition of iron in the
sinoatrial node, atrioventricular node, and the cardiac conduction system, as well as oxidative
stress. (33)
Early recognition of cardiac disorders is crucial and allows for the avoidance of permanent
complications. Screening for DCM and RCM is performed using transthoracic
echocardiography, while cardiac rhythm disorders are detected with Holter ECG monitoring.
2. Liver
The liver is the main iron storage site in the body, which makes it the organ most susceptible
to iron overload. (34) The most common hepatic complications of hereditary hemochromatosis
(HH) are liver cirrhosis and hepatocellular carcinoma (HCC). Iron accumulation in hepatocytes
leads to their damage and the development of fibrosis, which then progresses to cirrhosis and
HCC. (35) The risk of liver cirrhosis in patients with HH is 13 times higher than in the general
population. (6)
Hepatocellular carcinoma is the most common primary malignant tumor of the liver. It
originates from hepatocytes and most often develops on the basis of liver cirrhosis. HCC occurs
in 8-10% of patients with HH and is the cause of 45% of deaths in HH. (35) Patients with HH
have a 20-fold higher risk of developing HCC over their lifetime compared to the general
population. (2, 36) The risk of developing HCC in patients with HH is further increased by
chronic HBV infection and alcoholism. (35) Alcohol increases iron absorption and accelerates
liver damage. (6) Hepatocellular carcinoma, if detected early enough, can be effectively treated.
The treatment of choice is radical resection or liver transplantation - possible for patients who
meet the Milan criteria, i.e., a single tumor ≤ 5 cm or up to three separate tumors, none larger
than 3 cm. (37) Resection is performed for tumors localized within one lobe, without vascular
invasion, metastasis, and with preserved liver function. (38) In advanced-stage HCC, sorafenib
- a multi-kinase inhibitor with both antiproliferative and antiangiogenic activity - has proven
effectiveness. (39) In palliative treatment, ablative therapy and transarterial chemoembolization
(TACE) are used, which involves direct administration of appropriately large doses of
cytostatics to the arteries supplying the tumor.
3. Hypogonadism, Infertility
Approximately 50% of men with hereditary hemochromatosis experience sexual
dysfunctions such as erectile problems, ejaculation issues, reduced libido, decreased body hair,
impotence, less commonly gynecomastia, and infertility. Hypogonadotropic hypogonadism is
11
the second most common endocrinological complication in HH after diabetes, occurring in
about 10% of cases. (40) The mechanism of hypogonadism in HH includes damage to the
pituitary gland as well as dysfunctions in the gonadotropic axis - reduced production of Follicle
Stimulating Hormone (FSH) and Luteinizing Hormone (LH), but also direct damage to the
testicles and reproductive cells. In some cases, the testicles atrophy due to insufficient secretion
of gonadotropins, secondary to iron accumulation in the pituitary gland. (41) A decrease in LH
levels results in reduced testosterone production by Leydig cells, leading to decreased sexual
drive and ejaculation problems. Physiologically, FSH acting on Sertoli cells stimulates
spermatogenesis and ensures the proper development of the seminiferous tubules. (42)
Histological examination of the testicles in patients with HH showed arrest of sperm maturation
at the spermatocyte stage, associated with iron deposition in endothelial cells and perivascular
spaces. In females, symptoms of hypogonadism include secondary amenorrhea, loss of libido,
abnormal menstrual cycles with lack of ovulation, infertility, premature menopause, and loss
of body hair.
Hypogonadism in HH is more frequent and severe in males. In females, physiological
regulators of iron concentration include regular iron loss during menstruation, lactation,
pregnancy, and childbirth.
The treatment for hypogonadism focuses on addressing the underlying condition, HH.
Normal pituitary function can be restored within a few months. During this time, replacement
therapy is recommended - testosterone for men and estrogens and progesterone for women. (41)
4. Diabetes
Diabetes occurs in approximately 20% of patients with HH (Hereditary Hemochromatosis).
The pathogenesis of diabetes development in the course of HH is multifactorial. Most likely,
the primary factor is the loss of insulin secretion ability caused by the deposition of iron in the
pancreas. Secondary roles are played by insulin resistance, liver cirrhosis, and metabolic
syndrome. (43) The effectiveness of phlebotomy in treating diabetes is dubious, with scientific
research results being contradictory. It is certain, however, that phlebotomy improves insulin
secretion in the early stages of the disease. (44) The frequency of occurrence of microvascular
and macrovascular complications is similar to that in the general diabetic population. (45)
12
5. Arthritis
Arthritis symptoms are common in patients with symptomatic hereditary hemochromatosis
and can significantly impair their quality of life. The mechanism underlying the development
of arthritis associated with excess iron levels remains not fully understood. The most commonly
affected joints are the metacarpophalangeal joints, wrist joints, knee joints, hip joints, and
shoulder joints. Radiological examinations of hand joints often reveal the presence of
osteophytes, joint space narrowing, bone sclerosis, and subchondral cysts. In the differential
diagnosis of arthritis in the course of hemochromatosis, it is important to consider diseases
associated with CPPD deposition (calcium pyrophosphate dihydrate deposits), which can be
challenging as both conditions may present similar radiographic appearances. Iron is known to
impede the removal of CPPD crystals from the joint, which can exacerbate inflammation
symptoms. The symptoms of arthritis in HH can also resemble those of osteoarthritis or
rheumatoid arthritis. (46, 47)
According to current research, there is a strong correlation between arthritis in the course
of hemochromatosis and advanced liver fibrosis. The absence of arthritis indicates a low
probability of advanced liver fibrosis. The presence of arthritis in the course of the disease
might serve as a marker for advanced liver fibrosis. (48)
Treatment of arthritis includes the use of nonsteroidal anti-inflammatory drugs (NSAIDs),
rehabilitation, and surgical interventions, including joint arthroplasty. (49)
Treatment
The cornerstone of treatment for hereditary hemochromatosis is phlebotomy, a
procedure involving blood removal to eliminate excess iron from the body. The treatment
protocol includes an induction phase, a maintenance phase, and a monitoring phase. During the
induction phase, 350-500 ml of blood containing approximately 250 mg of iron is drawn every
1-2 weeks. Hemoglobin levels must be checked prior to each blood draw - if the hemoglobin
concentration is <11-12 g/dl, the phlebotomy should be postponed. Ferritin levels should be
monitored approximately every four sessions. Phlebotomy is repeated until ferritin serum levels
are reduced to <50 ng/ml and transferrin saturation falls below 50%. The maintenance phase
consists of 2-4 blood draws per year, aiming to keep ferritin levels within the range of
approximately 50-100 mg/l. Ferritin levels should subsequently be monitored approximately
every 6 months. A potential complication of HH that may not respond to phlebotomy treatment
13
is arthritis. Patients with cardiovascular or hepatic complications may not tolerate this treatment
well. (6, 29, 50)
An alternative to phlebotomy is therapeutic erythrocytapheresis (TEA), which involves
the extraction of erythrocytes from whole blood. This method is specifically recommended for
patients with advanced complications of the cardiovascular system and liver, who exhibit poor
tolerance to the hypovolemia induced by traditional phlebotomy. Erythrocytapheresis is a
modern, efficient method (it removes iron from the body faster than phlebotomy) and is better
tolerated by patients than phlebotomy, although it is associated with higher costs. TEA can be
used in conjunction with deferoxamine therapy, an iron-chelating agent. (26, 50, 51, 52)
Iron chelation therapy is used in severe cases of hereditary hemochromatosis (HH), particularly
in patients who have poor tolerance to blood removal, such as those with advanced heart failure.
(29, 53) The most commonly used iron chelating agent is deferoxamine. Deferoxamine has low
oral bioavailability, therefore it is administered intravenously or subcutaneously, and it has a
short half-life, requiring frequent applications. Deferoxamine is particularly beneficial in
cardiac hemochromatosis – it reduces iron load in the heart muscle, improves left ventricular
function, and prolongs survival. (21) Side effects of deferoxamine include: hypotension and
shock, visual and auditory disturbances (ophthalmic and audiologic evaluations are
recommended before initiating therapy), allergic reactions, skin reactions, acute respiratory
distress, and infections caused by Yersinia enterocolitica and Yersinia pseudotuberculosi.
Alternatives to deferoxamine include orally administered iron chelators - deferiprone and
deferasirox. Side effects of these agents can include agranulocytosis, liver fibrosis, renal
damage, and neurological disorders. The use of iron chelating drugs can cause a reddish-brown
discoloration of the urine. (54)
Hereditary hemochromatosis is not a contraindication to blood donation. (26)
Patients with hereditary hemochromatosis (HH) should maintain a normal, well-
balanced diet; there is no need to exclude iron-containing foods. It is advisable to avoid alcohol
consumption due to its hepatotoxic properties and raw seafood because of the increased risk of
septicemia caused by the gram-negative bacterium Vibrio vulnificus. (6, 29, 44)
Conclusions
Hereditary hemochromatosis (HH) is a disease entity that is asymptomatic in most
patients. The occurrence of the classic triad of HH symptoms - diabetes, skin hyperpigmentation,
14
and liver cirrhosis - is now rare. (47) It is extremely important to measure ferritin levels (iron
storage) and transferrin saturation, particularly in patients with unexplained hypogonadism,
cardiac disorders, diabetes, or arthritis. Diagnosis is based on genetic testing - identifying
mutations in genes, most commonly in the HFE gene. The average time from the appearance
of the first symptoms of the disease to diagnosis ranges from 5 to 8 years. (6) Early diagnosis
is crucial in preventing organ damage, including hepatocellular carcinoma, which is the cause
of death in 45% of HH patients. Available treatment methods - phlebotomy, therapeutic
erythrocytapheresis, and iron chelating drugs - are simple, inexpensive, and widespread. (13)
Early detection and treatment of HH can result in a lifespan comparable to the general
population. (55)
Conceptualization: Dominika Prystacka-Szar
Methodology: Dominika Prystacka-Szar, Wenancjusz Stołowski
Software: not applicable
Formal analysis: Dominika Prystacka-Szar, Magdalena Waśniowska
Investigation: Jakub Siemko, Dominika Prystacka-Szar, Justyna Stadler-Szajda
Resources: Dominika Prystacka-Szar, Justyna Stadler-Szajda, Natalia Rulewska
Writing - rough preparation: Dominika Prystacka-Szar, Jakub Siemko, Filip Grabowski
Writing - review and editing: Natalia Rulewska, Filip Grabowski, Adrianna Czyżnikiewicz
Visualization: Dominika Prystacka-Szar, Dagmara Neska, Magdalena Bujak
Supervision: Dominika Prystacka-Szar, Magdalena Waśniowska, Magdalena Bujak
Project administration: Dominika Prystacka-Szar
All authors have read and agreed with the published version of the manuscript.
Funding Statement:
Study did not receive special funding.
Institutional Review Board Statement:
Not applicable.
Informed Consent Statement:
Not applicable.
15
Data Availability Statement:
Not applicable.
Conflict of Interest Statement:
The authors of the paper report no conflicts of interest.
In preparing this work, the authors used ChatGPT (chatGPT.com) as a tool for translation
support in preparing this work. After using this tool, the authors have reviewed and edited the
content as needed and accept full responsibility for the substantive content of the publication.
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