Non-HFE hepatic iron overload.

Abstract

Numerous clinical entities have now been identified to cause pathologic iron accumulation in the liver. Some are well described and have a verified hereditary basis; in others the genetic basis is still speculative, while in several cases nongenetic iron-loading factors are apparent. The non- HFE hemochromatosis syndromes identifies a subgroup of hereditary iron loading disorders that share with classic HFE-hemochromatosis, the autosomal recessive trait, the pathogenic basis (i.e., lack of hepcidin synthesis or activity), and key clinical features. Yet, they are caused by pathogenic mutations in other genes, such as transferrin receptor 2 ( TFR2), hepcidin ( HAMP), hemojuvelin ( HJV) , and ferroportin ( FPN), and, unlike HFE-hemochromatosis, are not restricted to Caucasians. Ferroportin disease, the most common non- HFE hereditary iron-loading disorder, is caused by a loss of iron export function of FPN resulting in early and preferential iron accumulation in Kupffer cells and macrophages with high ferritin levels and low-to-normal transferrin saturation. This autosomal dominant disorder has milder expressivity than hemochromatosis. Other much rarer genetic disorders are associated with hepatic iron load, but the clinical picture is usually dominated by symptoms and signs due to failure of other organs (e.g., anemia in atransferrinemia or neurologic defects in aceruloplasminemia). Finally, in the context of various necro-inflammatory or disease processes (i.e., chronic viral or metabolic liver diseases), regional or local iron accumulation may occur that aggravates the clinical course of the underlying disease or limits efficacy of therapy.

• Authors: Antonello Pietrangelo, Angela Caleffi, Elena Corradini
• Journal: Seminars in liver disease (Semin Liver Dis) Vol. 31 Issue 3 Pg. 302-18 (Aug 2011) ISSN: 1098-8971 [Electronic] United States
• PMID: 21901660 (Publication Type: Journal Article, Review)
• Copyright: © Thieme Medical Publishers.

Chemical References

• Antimicrobial Cationic Peptides
• Cation Transport Proteins
• GPI-Linked Proteins
• HAMP protein, human
• HJV protein, human
• Hemochromatosis Protein
• Hepcidins
• Receptors, Transferrin
• TFR2 protein, human
• Transferrin
• metal transporting protein 1
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
• Iron
• Ceruloplasmin

Topics

• Antimicrobial Cationic Peptides (genetics)
• Cation Transport Proteins (deficiency, genetics)
• Ceruloplasmin (deficiency, metabolism)
• Diet (adverse effects)
• GPI-Linked Proteins (genetics)
• Hemochromatosis (diagnosis, epidemiology, genetics, metabolism)
• Hemochromatosis Protein
• Hemosiderosis (etiology)
• Hepcidins
• Humans
• Iron (metabolism)
• Iron Metabolism Disorders (metabolism)
• Liver (metabolism)
• Metal Metabolism, Inborn Errors (metabolism)
• Neurodegenerative Diseases (metabolism)
• Porphyria Cutanea Tarda (etiology)
• Receptors, Transferrin (genetics)
• Transferrin (deficiency, metabolism)