Hemochromatosis

it is iron overload in body due to dysregulation of Iron absorption.

1. Dr. Akif A.B Hemochromatosis

2. It is due to dysregulation of Iron absorption. Most commonly due to mutation in HFE gene at Chromosome 6. Most common gene is C282Y . Normal body iron stores = 3-4gm Daily iron absorption and excretion = 1mg/d in males and 1.5mg/day in females. In hemochromatosi daily absorption increases to 4mg/day whereas excretion remains same Introduction

3. Iron overload states

4. Genetic predisposition without manifestations Iron overload without symptoms Iron overload with symptoms (Fatigue) Iron overload with organ failure Clinical classification in C282Y Homozygotes

5. Non specific Liver Skin Heart Pituitary Joints Clinical features

6. These are the initial symptoms: Lethargy/ Fatigue : MC symptom of Hemochromatosis Skin discoloration Arthralgia Loss of Libido Features of Diabetes Mellitus. Non specific symptoms

7. Most commonly involved in Advanced disease Present in 95% patients of Advance disease Hepatomegaly Cirrhosis Hepatocellular carcinoma develops in 30% patients Liver

8. Metallic or sley grey Due to increase Iron and Melanin in Dermis Generalised and diffuse Known as Bronzing Skin

9. 65% of patients More prone in family history of Diabetes. Occurs due to Iron deposition in Pancreatic Islet cells. Diabetes mellitus

10. 25-50% patients Most commonly involves : 2 nd and 3 rd Metacarpo-Phalangeal Joint. Arthropathy

11. 15% patients Most common presentation : Congestive heart failure Cardiomyopathy occurs Cardiac Manifestations

12. Occurs in both sexes Occurs due to iron deposition in Pituitary Leading to Hypogonadotropic hypogonadism . Hypogonadism

13. Hypoadrenalism Hypothyroidism Hypoparathyroidism Rare manifestations

14. Transferrin saturation : >45% (Normal=22-45) Serum ferritin : Elevated 300->1000 (Normal =20-250µg/L) TIBC : Normal or slightly elevated Serum iron : Elevated Diagnosis

15. Serum iron is also elevated in Alcoholic liver disease but hepatic iron is not increased in it. So both Serum ferritin and Transferrin level should be used for diagnosis of Hemochromatosis . An increase in 1µg/L of Ferritin indicates Increase of 5mg of Iron Iron body stores

16. Phlebotomy Weekly or twice weekly 500ml blood is removed 500ml blood removes 200-250mg of Iron Total of 25gm of Iron need to be removed To be continued till serum ferritin levels : <50µg/L After that one phlebotomy every 3 monthly Treatment

17. Parenteral - Deferoxamine (Oral – Deferaxirox ) Removes 10-20mg Iron per day Less effective than Phlebotomy More costlier Indicated only in severe anemia and severe hypoalbuminemia where Phlebotomy cant be done Chelating agents

18. Iron supplementation should be avoided Vitamin C supplementation should be avoided Alcohol should be avoided Management of Cardiac failure, Heaptic failure and Diabetes is as routinely managed. Treatment cannot reverse Cirrhosis.

19. 5 year survival rate increases from 33-89% with phlebotomy Major cause of Death are : Cardiac failure Hepatic failure Hepatocellular carcinoma Portal hypertension Prognosis