Haemochromatosis type 3
| Haemochromatosis type 3 | |
|---|---|
| Other names | TFR2-related hemochromatosis[1] |
| Specialty | Hematology |
Haemochromatosis type 3 is a type of iron overload disorder associated with deficiencies in transferrin receptor 2. It exhibits an autosomal recessive inheritance pattern.[2][3][4] The first confirmed case was diagnosed in 1865 by French doctor Trousseau. Later in 1889, the German doctor von Recklinghausen indicated that the liver contains iron, and due to bleeding being considered to be the cause, he called the pigment "Haemochromatosis." [5] In 1935, English doctor Sheldon's groundbreaking book titled, Haemochromatosis, reviewed 311 patient case reports and presented the idea that haemochromatosis was a congenital metabolic disorder.[5] Hereditary haemochromatosis is a congenital disorder which affects the regulation of iron metabolism thus causing increased gut absorption of iron and a gradual build-up of pathologic iron deposits in the liver and other internal organs, joint capsules and the skin.[5] The iron overload could potentially cause serious disease from the age of 40-50 years. In the final stages of the disease, the major symptoms include liver cirrhosis, diabetes and bronze-colored skin. There are four types of hereditary hemochromatosis which are classified depending on the age of onset and other factors such as genetic cause and mode of inheritance.[6]
Signs and Symptoms
The presence of Haemochromatosis type 3 can be realized through its many signs and symptoms throughout bodily systems. Systems affected by Haemochromatosis type 3 include the skeletal, endocrine, cardiovascular, neurological, genitourinary, and integumentary systems.[7][8][9][10] There are also implications associated with a person's hematology, laboratory analysis results, and their liver.[6] The specific diseases and conditions that show a correlation with Haemochromatosis type 3 are the following:
| System | Symptom/Disease |
|---|---|
| Skeletal | Arthritis |
| Hematology | Anemia
Lymphopenia Neutropenia Thrombocytopenic Purpura |
| Genitourinary (Male) | Impotence
Decreased Libido Hypogonadism |
| Genitourinary (Female) | Amenorrhea |
| Endocrine | Diabetes |
| Neurologic | Fatigue |
| Abdomen, Liver | Cirrhosis
Fibrosis |
| Cardiovascular | Cardiomyopathy |
| Integumentary | Hyperpigmentation |
| Laboratory Abnormalities | Increased Serum Ferritin
Increased Serum Iron Increased Transferrin Saturation Increased Liver Transaminases |
Diagnosis
Like many genetic or rare diseases, diagnosis of haemochromatosis type 3 is challenging. In order to formulate a diagnosis healthcare professionals view medical history, symptoms, physical exam, and laboratory test results.[11]
Testing Resources:
The Genetic Testing Registry provides information about genetic tests for haemochromatosis type 3. There are 62 different clinical tests available including two biochemical Genetics tests and 60 molecular genetics tests. There is also one research test available.
- Clinical tests
- Biochemical genetics tests (2)
- Enzyme assay (2)
- Molecular genetics tests (60)
- Deletion/duplication analysis (22)
- Sequence analysis of select exons (12)
- Sequence analysis of the entire coding region (52)
- Targeted variant analysis (9)
- Biochemical genetics tests (2)
- Research Tests
- TFR2-Related Hereditary Haemochromatosis (1)[12]
Management or Treatment
Treatment for hemochromatosis type 3 may include reducing iron levels by removing blood (phlebotomy), iron chelation therapy, diet changes, and treatment for complications of the disease. The purpose of the treatment is to reduce the amount of iron in the body to normal levels, prevent or delay organ damage from excess iron, and maintain normal amounts of iron throughout the lifetime.[13] Phlebotomy helps to remove excess iron from the body. Most treatment begins with weekly therapeutic phlebotomy, occasionally treatment is initially twice a week if iron levels are elevated. Maintenance phlebotomy usually involved treatment every 2-4 months. Iron chelation therapy may be recommended for people that have other health issues as well.[13] Dietary recommendations may include avoiding alcohol and red meat. People with hemochromatosis are not recommended to take iron or vitamin C supplements.[13]
Genetics
Inheritance Pattern
Haemochromatosis type 3 is inherited in an autosomal recessive manner. Individuals with this disease exhibit a mutation or pathogenic effect in both copies of the TFR2 in each cell. People with only one copy of TFR2 that is affected are labeled as carriers. Carriers typically do not exhibit signs or symptoms of the disease.
When two carriers have children:
- 25% chance to have disease.
- 50% to become a carrier.
- 25% chance to have two unaffected copies of TFR2 gene.
This disease is shown to have reduced penetrance. Thus, some people with pathogenic variants of the TFR2 gene may never present symptoms related to the disease.[14]
Genes Involved
The two genes involved are HFE and BMP2. HFE-associated hereditary hemochromatosis is the most common type of inherited iron overload disorder.
Type of Mutations
Location of the Chromosome
The heterozygous mutation in the transferrin receptor-2 gene (TFR2) and the mutation in the hemochromatosis type 3 gene (HFE3) are the causes of hemochromatosis type 3.[15] These mutations are found on chromosome 7q22.[15] The location of the genes affected are at 7:100,620,419 on the DNA chromosome.[16]
Effects on Gene Products
Spectrum of Disease Severity
Epidemiology
The prevalence in the ethnic Norwegian population of homozygous and heterozygous inheritance is 0.8% and 12-15% respectively, which makes haemochromatosis one of the most common hereditary diseases in Norway.[17] Type 1 hemochromatosis is one of the most common genetic disorders in the United States, affecting about 1 million people. It most often affects people of Northern European descent. The other types of hemochromatosis are considered rare and have been studied in only a small number of families worldwide.[6]
References
- ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Hemochromatosis type 3". www.orpha.net. Retrieved 8 June 2019.
{{cite web}}: CS1 maint: numeric names: authors list (link) - ^ Roetto A, Totaro A, Piperno A, et al. (May 2001). "New mutations inactivating transferrin receptor 2 in hemochromatosis type 3". Blood. 97 (9): 2555–60. doi:10.1182/blood.V97.9.2555. PMID 11313241.
- ^ Roetto A, Daraio F, Alberti F, et al. (2002). "Hemochromatosis due to mutations in transferrin receptor 2". Blood Cells Mol. Dis. 29 (3): 465–70. doi:10.1006/bcmd.2002.0585. PMID 12547237.
- ^ Roetto A, Camaschella C (June 2005). "New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis". Best Pract Res Clin Haematol. 18 (2): 235–50. doi:10.1016/j.beha.2004.09.004. PMID 15737887.
- ^ a b c Johan Ulvik, Rune (20 December 2016). "Hereditary haemochromatosis through 150 years". Tidsskriftet. Retrieved 26 April 2021.
{{cite web}}: CS1 maint: url-status (link) - ^ a b c d "Hereditary hemochromatosis". MedlinePlus. 1 February 2019.
{{cite web}}: CS1 maint: url-status (link) Cite error: The named reference ":2" was defined multiple times with different content (see the help page). - ^ Camaschella, C.; Fargion, S.; Sampietro, M.; Roetto, A.; Bosio, S.; Garozzo, G.; Arosio, C.; Piperno, A. (1999-05-XX). "Inherited HFE-unrelated hemochromatosis in Italian families". Hepatology (Baltimore, Md.). 29 (5): 1563–1564. doi:10.1002/hep.510290509. ISSN 0270-9139. PMID 10216143.
{{cite journal}}: Check date values in:|date=(help) - ^ Camaschella, C.; Roetto, A.; Calì, A.; De Gobbi, M.; Garozzo, G.; Carella, M.; Majorano, N.; Totaro, A.; Gasparini, P. (2000-05). "The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22". Nature Genetics. 25 (1): 14–15. doi:10.1038/75534. ISSN 1061-4036. PMID 10802645.
{{cite journal}}: Check date values in:|date=(help) - ^ Griffiths, W.; Cox, T. (2000-10). "Haemochromatosis: novel gene discovery and the molecular pathophysiology of iron metabolism". Human Molecular Genetics. 9 (16): 2377–2382. doi:10.1093/hmg/9.16.2377. ISSN 0964-6906. PMID 11005792.
{{cite journal}}: Check date values in:|date=(help) - ^ Mattman, Andre; Huntsman, David; Lockitch, Gillian; Langlois, Sylvie; Buskard, Noel; Ralston, Diana; Butterfield, Yaron; Rodrigues, Pedro; Jones, Steven; Porto, Graça; Marra, Marco (2002-08-01). "Transferrin receptor 2 (TfR2) and HFE mutational analysis in non-C282Y iron overload: identification of a novel TfR2 mutation". Blood. 100 (3): 1075–1077. doi:10.1182/blood-2002-01-0133. ISSN 0006-4971. PMID 12130528.
- ^ "Hemochromatosis type 3 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2021-04-26.
- ^ "Hemochromatosis type 3 - Conditions - GTR - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-04-26.
- ^ a b c "Hemochromatosis type 3". Genetics and Rare Diseases Information Center. 15 February 2018.
{{cite web}}: CS1 maint: url-status (link) - ^ "Hemochromatosis type 3 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2021-04-26.
- ^ a b Roychoudhury, A. K. (1977-12-29). "Gene diversity in Indian populations". Human Genetics. 40 (1): 99–106. doi:10.1007/BF00280836. ISSN 0340-6717. PMID 604250.
- ^ "Genome Data Viewer - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-04-26.
- ^ Johan Ulvik, Rune (20 December 2016). "Hereditary haemochromatosis through 150 years". Tidsskriftet. Retrieved 26 April 2021.
{{cite web}}: CS1 maint: url-status (link)
External links
 | This article about a disease of the blood or immune system is a stub. You can help Wikipedia by expanding it. |
 | This genetic disorder article is a stub. You can help Wikipedia by expanding it. |