Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review
Abstract
:1. Introduction
Body Iron Homeostasis and Risk Factors of Iron Overload
- (a)
- HFE p.C282Y homozygosity—the greatest risk factor;
- (b)
- positive family history for HC in the first-line relatives;
- (c)
- Northern European ethnicity—the disease is less prevalent in populations of Afro-American, Hispanic, and Asian origin;
- (d)
- male gender—men are susceptible to developing HC symptoms at an earlier age; however, females’ risk increases after menopause or a hysterectomy.
2. Gene Mutations in Hemochromatosis
3. The Current Classification of Hemochromatosis
4. Clinical Presentation of Hemochromatosis Regardless of Phlebotomy Treatment
4.1. Hemochromatosis and the Skeletomuscular System
4.2. Hemochromatosis and the Central Nervous System
4.3. Hemochromatosis and the Liver
4.4. Hemochromatosis and the Cardiovascular System
4.5. Hemochromatosis and the Endocrine System
4.6. Hemochromatosis and the Skin
5. Diagnostic Approach to the Patient with Iron Overload Suspicion
5.1. Blood Tests
- Serum transferrin saturation (TSAT)—is calculated as the ratio between serum iron and total iron-binding capacity (TIBC). The higher-than-normal value of TSAT (above 45%) remains the earliest disease indicator present in all hemochromatosis subtypes [24]. However, increased TSAT is also observed in other disorders (e.g., hemolysis, cytolysis) or decreased blood transferrin concentration (e.g., hepatocellular failure, proteinuria, malnutrition, genetic alterations) [73]. Normal or even lower TSAT values can be observed in patients with ferroportin disease or hereditary aceruloplasminemia despite overt iron overload [74,75].
- Serum ferritin level (SF)—is a commonly used diagnostic marker for the evaluation of iron storage in the body, although not very accurate [76]. The concentration of ferritin in the blood is influenced by many factors, as it is an acute-phase protein. Elevated SF levels (above 300 μg/L in men and postmenopausal women; above 200 μg/L in premenopausal women) require precise explanation before they are assigned to iron overload. Other conditions of hyperferritinemia, such as metabolic syndrome, alcoholism, inflammation, and marked cytolysis, should be ruled out [12]. Nevertheless, SF is an important prognostic factor in patients with HC. It is a predictor of advanced liver fibrosis and cirrhosis in patients with previously diagnosed hemochromatosis.
5.2. Genetic Testing
5.3. Additional Diagnostic Assessment for Hemochromatosis
- Liver enzymes and function tests—the pattern of liver function alterations helps monitor liver damage in the course of HC.
- Liver biopsy—determining the hepatic iron concentration (HIC) is rarely required to establish a final HC diagnosis; therefore, currently, genetic examination and imaging testing have replaced liver biopsy. Occasionally, it may be used to confirm or exclude other co-existing chronic liver diseases and to determine the degree of hepatic fibrosis, especially in cases with p.C282Y homozygosity and SF above 1000 ng/mL. HIC assessment may also be indicated in cases of suspected genetic iron overload with negative results towards common mutations including p.C282Y, p.H63D, and p.S65C. In remaining cases, liver biopsy is an option for individual consideration [81]. HIC assessed in a proper quality biopsy sample that is sample gross weight equal to or above 1 mg dry weight remains an accurate measure of entire hepatic iron concentration [82].
- Magnetic resonance imaging (MRI)—the reference imaging technique for the evaluation and quantification of HIC; a noninvasive and accurate alternative to a liver biopsy with an excellent correlation between both aforementioned procedures; useful for identification of iron overload, its rating, and the assessment of treatment results [83,84].
- Superconducting quantum interference device biomagnetic liver susceptometry (SQUID-BLS)—a noninvasive diagnostic device with very limited availability, used for HIC assessment; since hepatic iron can change its magnetic susceptibility, SQUID-BLS can quantify liver magnetic susceptibility and therefore determine liver iron concentration [80,85]. The procedure is available in very few specialized centers only.
6. Screening of Healthy People for Hemochromatosis
7. Treatment of Hemochromatosis
7.1. Phlebotomy—The First-Line Treatment for Iron Depletion
7.2. Erythrocytapheresis as an Alternative to Phlebotomy
7.3. Iron Chelators as a Therapeutic Alternative in Hemochromatosis
7.4. Proton Pump Inhibitors—An Adjunct Therapy for Hemochromatosis?
7.5. Liver Transplantation for Hemochromatosis
7.6. Recommended Lifestyle and Diet Modifications in Patients with Hemochromatosis
- withdrawal of additional iron sources such as iron supplements, iron-containing multivitamins, and iron-fortified foods and drinks (e.g., breakfast cereals, sports energy bars, etc.);
- recommendation of a varied vegetarian, semi-vegetarian, or flexitarian diet;
- avoidance of vitamin C supplements which increase iron absorption, but there is no need to restrict natural vitamin C in their diet (fruit and vegetables); fruit juices should be consumed between meals;
- recommendation of complete alcohol abstinence as its hepatotoxic impact aggravates liver damage; there is no safe alcohol amount;
8. Hemochromatosis in Women—Pregnancy and Fertility Issues
9. Future Directions in Hemochromatosis
10. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
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Organ/System | Symptoms |
---|---|
Skeletomuscular system | arthralgia, arthritis, chondrocalcinosis, reduced bone mineral density, fatigue, weakness |
Central nervous system | lack of energy (lethargy), irritability, memory fog, mood swings, depression, anxiety, movement disorders, tremors |
Liver | high liver enzymes, hepatosplenomegaly, liver fibrosis and cirrhosis, hepatocellular carcinoma |
Cardiovascular system | cardiomyopathy, arrhythmia, heart failure |
Endocrine system | hypogonadism, testicular atrophy, reproductive disorders with loss of libido, impotence, amenorrhea, hyperglycemia, diabetes mellitus, hypopituitarism |
Skin | bronze or gray skin tone (hypermelanotic pigmentation), hair loss, porphyria cutanea tarda (?) |
Immune system | immune defects, infections |
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Szczerbinska, A.; Kasztelan-Szczerbinska, B.; Rycyk-Bojarzynska, A.; Kocki, J.; Cichoz-Lach, H. Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review. J. Clin. Med. 2024, 13, 3660. https://doi.org/10.3390/jcm13133660
Szczerbinska A, Kasztelan-Szczerbinska B, Rycyk-Bojarzynska A, Kocki J, Cichoz-Lach H. Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review. Journal of Clinical Medicine. 2024; 13(13):3660. https://doi.org/10.3390/jcm13133660
Chicago/Turabian StyleSzczerbinska, Agnieszka, Beata Kasztelan-Szczerbinska, Anna Rycyk-Bojarzynska, Janusz Kocki, and Halina Cichoz-Lach. 2024. "Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review" Journal of Clinical Medicine 13, no. 13: 3660. https://doi.org/10.3390/jcm13133660
APA StyleSzczerbinska, A., Kasztelan-Szczerbinska, B., Rycyk-Bojarzynska, A., Kocki, J., & Cichoz-Lach, H. (2024). Hemochromatosis—How Not to Overlook and Properly Manage “Iron People”—A Review. Journal of Clinical Medicine, 13(13), 3660. https://doi.org/10.3390/jcm13133660