Hemochromatosis

__**Hemochromatosis **__

 //Caused by Mutations in:// >> 
 * Root Cause: **
 * Constant influx of dietary iron into blood stream leads to perpetually high iron levels in body
 * HFE MHC protein (Hemochromatosis Major Histocompatibility Complex):
 * Most common cause of hemochromatosis – other causes are very rare
 * Mutations C282Y prevents essential disulfide bond from forming1
 * Mutations H63D, and/or S65C can also cause disease
 * TfR2 (Transferrin receptor 1)
 * Nonesense mutation Y250X
 * HJV protein (Hemojuvelin)
 * Mutation G320
 * FPN (Ferroportin) transmembrane protein
 * Mutations C326S or C326Y cause hepcidin resistance


 * Affected organs: **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Blood – constantly high levels of iron
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Liver – if left untreated long term, can lead to cirrhosis
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Heart – if left untreated long term, can lead to cardiomyopathy3


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Origin and History: **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Armand Trousseau
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">French physician who first described hemochromatosis
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">in 19th century, conducted an autopsy on a patient with very dense, grayish-yellow liver
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Joseph Sheldon
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Correctly hypothesized hemochromatosis was hereditary and caused by malfunction in iron metabolism
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Simon et al.
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Found association between hemochromatosis and an MHC complex on chromosome 6
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Fedder and Wolff
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Identified the exact location of HFE gene on chromosome 6 at the p.22.2. region2


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Common symptoms: **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Chronic asthenia (physical weakness) – symptoms are often confused with anemia (lack of iron)
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Sexual fatigue – especially in men
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Arthralgia (joint pain) – especially in knees, second and third metacarpophalangeal joints
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Dry skin
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Deformation of nails3


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Standard treatments: **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Phlebotomy
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Periodic, controlled blood-letting is the easiest method to remove the excess iron
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Iron chelators
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Chelating drugs: Ferriprox and Exjade can cause agranulocytosis so phlebotomy is the conventional method of treatment4


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Current Research: **
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Effect of phlebotomy on lipid metabolism in subjects with hereditary hemochromatosis
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Patients suffering from hemochromatosis are often also afflicted by hypertriglyceridemia
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">A study was conducted to determine whether phlebotomies can decrease blood triglyceride levels
 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">It was discovered phlebotomy does decrease triglyceride levels without affecting blood glucose or cholesterol5


 * <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">References: **
 * 1) <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Distante, S. (2006) Genetic predisposition to iron overload: prevalence and phenotypic expression of hemochromatosis-associated hfe-c282y gene mutation. Scandinavian Journal of Clinical & Laboratory Investigation 66: 81–100.
 * 2) <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Brissot, P., Guyader, D., Loreal, O., Laine, F., Guillygomarc'h, A., Moirand, R., & Deugnier, Y. (2000). Clinical aspects of hemochromatosis. Transfusion Science 23: 193–200.
 * 3) <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Pietrangelo A., (2010) Hereditary Hemochromatosis: Pathogenesis, Diagnosis and Treatment. Reviews in Basic and Clinical Gastroenterology and Hepatology 139: 393–408.
 * 4) <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Moyer, T.P., Highsmith W.E., Smyrk T.C., Gross J.B. Jr (2011). Hereditary hemochromatosis: laboratory evaluation. Clinica Chimica Acta 412: 1485–1492.
 * 5) <span style="font-family: 'Times New Roman',Times,serif; font-size: 140%;">Casanova-Esteban, P.,Guiral, N., Andres E., Gonzalvo C., Mateo-Gallego R., Giraldo, P., Paramo, J.A., Civeira F (2011). Effect of phlebotomy on lipid metabolism in subjects with hereditary hemochromatosis. Metabolism 60: 830–834.