type 2 Hemochromatosis

An autosomal recessive form of congenital hemochromatosis characterized by severe iron loading and organ failure before 30 years of age. It is characterized by by a triad of HEMOSIDEROSIS; HEART DISEASE; LIVER CIRRHOSIS; DIABETES MELLITUS and abnormal skin pigmentation. Mutations in the HJV gene have been identified. OMIM: 602390

Also Known As:

Networked: 82 relevant articles (2 outcomes, 2 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Iron Overload
2.	Hemochromatosis (Bronze Diabetes)
3.	Pituitary Neoplasms (Pituitary Adenoma)
4.	Cardiomyopathies (Cardiomyopathy)
5.	Heart Failure

Experts

1.	Camaschella, Clara: 8 articles (12/2015 - 10/2002)
2.	Brissot, Pierre: 5 articles (08/2014 - 01/2004)
3.	Papanikolaou, George: 5 articles (11/2011 - 01/2003)
4.	Ganz, Tomas: 5 articles (11/2008 - 08/2003)
5.	Roetto, Antonella: 5 articles (02/2005 - 10/2002)
6.	Nemeth, Elizabeta: 4 articles (11/2008 - 01/2004)
7.	Tatsumi, Yasuaki: 3 articles (08/2020 - 03/2012)
8.	Silvestri, Laura: 3 articles (12/2015 - 05/2007)
9.	Bardou-Jacquet, Edouard: 3 articles (08/2014 - 07/2008)
10.	Jouanolle, Anne-Marie: 3 articles (04/2014 - 01/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to type 2 Hemochromatosis:

1.	IronIBA 01/01/2021 - "Juvenile hemochromatosis is characterized by an early onset of excess accumulation of iron in various organs. " 01/26/2018 - "Juvenile hemochromatosis is the most severe form of iron overloading phenotype. " 10/16/2017 - "Juvenile hemochromatosis (JH) is a rare condition classified as an autosomal recessive disorder that leads to severe iron absorption. " 07/07/2015 - "To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14(-/-) mice with Hfe(-/-) and Hfe2(-/-) mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. " 05/01/2009 - "Mutations in hemojuvelin (HJV) cause severe juvenile hemochromatosis, characterized by iron loading of the heart, liver, and pancreas. "
2.	Glucose (Dextrose)FDA LinkGeneric 03/01/2007 - "Glucose metabolism, insulin secretion and insulin sensitivity in juvenile hemochromatosis. " 03/01/2007 - "Present data indicate that in juvenile hemochromatosis, the efficacy of the chelation therapy and probably the chronic interval required to restore normal iron concentration both play important roles in the formation of glucose metabolism characteristics."
3.	GonadotropinsIBA 03/01/2012 - "Before diagnosing CHH, however, it is necessary to rule out a pituitary tumor or pituitary infiltration by imaging studies, juvenile hemochromatosis, and a systemic disorder that, by undermining nutritional status, could affect gonadotropin secretion and pubertal development. "
4.	HepcidinsIBA 03/15/2012 - "Identification of a novel mutation in the HAMP gene that causes non-detectable hepcidin molecules in a Japanese male patient with juvenile hemochromatosis." 07/02/2009 - "Juvenile hemochromatosis (JH) is the most severe form, usually caused by mutations in hemojuvelin (HJV) or hepcidin (HAMP). " 01/01/2007 - "Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis." 09/01/2005 - "We sequenced the coding region and the exon-intron boundaries of genes associated with juvenile hemochromatosis, HAMP and HJV encoding hepcidin and hemojuvelin respectively. " 02/15/2005 - "Juvenile hemochromatosis is associated with hepcidin or hemojuvelin mutations, and these patients have low or absent urinary hepcidin. "
5.	metal transporting protein 1 (ferroportin)IBA 01/01/2021 - "Appropriate Clinical Genetic Testing of Hemochromatosis Type 2-4, Including Ferroportin Disease." 01/01/2006 - "Among them the classical form, juvenile hemochromatosis with severe course and circulatory insufficiency, and ferroportin disease are presented. " 08/01/2014 - "Rare forms of hereditary hemochromatosis include type 2 (A and B, juvenile hemochromatosis caused by HJV and HAMP mutation), type 3 (related to TFR2 mutation), and type 4 (A and B, ferroportin disease). " 03/01/2006 - "Four types of inherited iron overload have been recognized: type 1, the most common form with an autosomal recessive inheritance, is associated with mutations in the HFE gene on chromosome 6; type 2 (juvenile hemochromatosis) is an autosomal recessive disorder with causative mutations identified in the HJV gene (subtype A) on chromosome 1 and the HAMP gene (subtype B) on chromosome 19; type 3 has also an autosomal recessive inheritance with mutations in the TfR2 gene on chromosome 3; type 4 is an autosomal dominant condition with heterozygous mutations in the ferroportin 1 gene on chromosome 2. In this review, the genetics, pathophysiology, diagnosis, clinical features, and management of these different types of hereditary hemochromatosis are briefly discussed." 08/28/2023 - "They are non-HFE hemochromatosis type 2A (HFE2, encoding HJV), type 2B (HAMP, encoding hepcidin), type 3 (TFR2, encoding transferring receptor-2), and types 4A and B (SLC40A1, encoding ferroportin. "
6.	Transferrin Receptors (Transferrin Receptor)IBA 12/01/2015 - "Transferrin receptor 2 mutations in patients with juvenile hemochromatosis phenotype." 09/01/2007 - "Four genes have been implicated in hereditary hemochromatosis: HFE and TFR2 (which codes for the second transferrin receptor), both involved in adult forms of hereditary hemochromatosis, and HAMP and HJV, which code for hepcidin and hemojuvelin, respectively, and are responsible for juvenile hemochromatosis. " 01/01/2006 - "At least three of these entities (HFE hemochromatosis, juvenile hemochromatosis and transferrin receptor 2 hemochromatosis) involve systemic hepcidin deficiency as a key pathogenetic factor. " 10/01/2005 - "Rare defects, including mutations in the transferrin receptor 2 (TFR2) gene, have also been identified in pedigrees affected with "non-HFE hemochromatosis." Homozygous mutations in the newly identified genes encoding hemojuvelin (HFE2) and hepcidin (HAMP) cause juvenile hemochromatosis. " 01/01/2004 - "Genetic hemochromatosis now corresponds to six diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 whose gene is hepcidine (HAMP). "
7.	Proteins (Proteins, Gene)FDA Link 10/01/2015 - "Hemojuvelin (HVJ) is a membrane-bound and soluble protein in mammals that is responsible for the iron overload condition known as juvenile hemochromatosis. " 04/01/2008 - "Juvenile hemochromatosis is a severe and rapidly progressing hereditary disorder of iron overload, and it is caused primarily by defects in the gene encoding repulsive guidance molecule c/hemojuvelin (RGMc/HJV), a recently identified protein that undergoes a complicated biosynthetic pathway in muscle and liver, leading to cell membrane-linked single-chain and heterodimeric species, and two secreted single-chain isoforms. " 07/01/2007 - "Mutations in hemochromatosis type 2 (HFE2), which encodes the protein hemojuvelin (HJV), result in the absence of hepcidin and an early-onset form of iron overload disease. " 08/01/2005 - "Human mutations in the glycosylphosphatidylinositol-anchored protein hemojuvelin (HJV; also known as RGMc and HFE2) cause juvenile hemochromatosis, a severe iron overload disease, but the way in which HJV intersects with the iron regulatory network has been unclear. " 01/01/2019 - "Juvenile hemochromatosis (JH) is related to hemojuvelin mutation, which is a regulatory peptide of the hepcidin protein, which regulates iron absorption. "
8.	Ferritins (Ferritin)IBA 11/18/2023 - "Cardiomyopathy and Cardiogenic Shock Caused by Juvenile Hemochromatosis Improving with Guideline-Directed Medical Therapy Despite High Ferritin Levels." 01/01/2004 - "Genetic hemochromatosis now corresponds to six diseases, namely classical hemochromatosis HFE 1; juvenile hemochromatosis HFE 2 due to mutations in an unidentified gene on chromosome 1; hemochromatosis HFE 3 due to mutations in the transferrin receptor 2 (TfR2); hemochromatosis HFE 4 caused by a mutation in the H subunit of ferritin; and hemochromatosis HFE 6 whose gene is hepcidine (HAMP). " 11/15/2008 - "Serum hepcidin concentrations were undetectable or low in patients with iron deficiency anemia (ferritin < 10 ng/mL), iron-depleted HFE hemochromatosis, and juvenile hemochromatosis. " 12/01/2007 - "We used a standard 96-well microplate with a single PCR condition in an adaptation of the SCAIP (single-condition amplification with internal primer) method to sequence the HFE (hemochromatosis), HAMP (hepcidin antimicrobial peptide), HFE2/HJV [hemochromatosis type 2 (juvenile)], SLC40A1 (ferroportin), and TFR2 (transferrin receptor 2) genes, and the 5' untranslated region of the FTL (ferritin, light polypeptide) gene. "
9.	5' Untranslated Regions (5' UTR)IBA 03/01/2009 - "Concerning HAMP, the deleterious mutation 5'UTR -25G-->A was found once, associated with Juvenile Hemochromatosis. " 01/01/2007 - "We describe a point mutation creating an additional ATG codon in the 5' untranslated region (UTR) of the HAMP gene, in a patient with juvenile hemochromatosis. " 12/01/2007 - "We used a standard 96-well microplate with a single PCR condition in an adaptation of the SCAIP (single-condition amplification with internal primer) method to sequence the HFE (hemochromatosis), HAMP (hepcidin antimicrobial peptide), HFE2/HJV [hemochromatosis type 2 (juvenile)], SLC40A1 (ferroportin), and TFR2 (transferrin receptor 2) genes, and the 5' untranslated region of the FTL (ferritin, light polypeptide) gene. "
10.	Bone Morphogenetic Proteins (Bone Morphogenetic Protein)IBA 10/01/2008 - "The delayed export and retention in the endoplasmic reticulum of some N-terminal mutants could contribute to the pathogenesis of juvenile hemochromatosis, reducing a prompt response of bone morphogenetic protein. " 10/25/2018 - "Iron-dependent hepcidin induction requires hemojuvelin (HJV), a bone morphogenetic protein (BMP) coreceptor that is disrupted in juvenile hemochromatosis, causing dramatic hepcidin deficiency and tissue iron overload. " 04/01/2015 - "The matriptase (MT)-2 protein (encoded by the TMPRSS6 gene) regulates hepcidin expression by cleaving hemojuvelin [HJV/hemochromatosis type 2 (HFE2)], a bone morphogenetic protein (BMP) coreceptor in the hepcidin regulatory pathway. "

Therapies and Procedures

1.	Chelation Therapy (Therapy, Chelation) 01/26/2018 - "This rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy." 01/26/2018 - "Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report." 03/01/2007 - "Present data indicate that in juvenile hemochromatosis, the efficacy of the chelation therapy and probably the chronic interval required to restore normal iron concentration both play important roles in the formation of glucose metabolism characteristics."
2.	Therapeutics 04/01/2014 - "Juvenile Hemochromatosis, Genetic Study and Long-term Follow up after Therapy." 12/01/2005 - "We believe that hypogonadotropic hypogonadism in juvenile hemochromatosis may be reversible by a consequent venesection therapy probably because treatment was intensive and promptly introduced at a young age." 11/18/2023 - "Cardiomyopathy and Cardiogenic Shock Caused by Juvenile Hemochromatosis Improving with Guideline-Directed Medical Therapy Despite High Ferritin Levels." 01/01/2007 - "Reversal of cardiac complications by deferiprone and deferoxamine combination therapy in a patient affected by a severe type of juvenile hemochromatosis (JH)." 11/18/2023 - "This case highlights the importance of suspecting juvenile hemochromatosis in young patients with dilated cardiomyopathy, and demonstrates the key role of Guideline-Directed Medical Therapy in addition to therapeutic phlebotomy and iron-chelators."
3.	Aftercare (After-Treatment) 04/01/2016 - "Juvenile Hemochromatosis in Iran: A Case Report with 5-Year Follow-up after Treatment."