Recommendations for the Diagnosis and Management of Hemochromatosis

Transcription

1 Recommendations for the Diagnosis and Management of Hemochromatosis

2 Individuals with hemochromatosis retain too much iron which may be toxic to the tissues in which it is stored. Acquired hemochromatosis: Occurs in individuals with chronic anemia who are transfusion dependent. Alcoholics and individuals with chronic viral hepatitis or other parenchymal liver disease can acquire excess iron stores in the liver Genetic hemochromatosis: Common form is due to mutations in a gene called HFE. This is an autosomal recessive condition and, therefore, both alleles of HFE must be abnormal for risk to occur. Other genetic types are extremely rare

3 Risk factors Northern European heritage (prevalence approximately 1/300) Symptoms are most often not present before middle-age Iron Storage Liver Heart Pancreas Skin Joints Pituitary Testis Consequences Can lead to cirrhosis and, rarely, hepatocellular carcinoma Can lead to congestive heart failure and/or arrhythmia due to cardiomyopathy Can lead to diabetes Can lead to abnormal skin colour (bronze or grey) Can lead to arthritis, especially of 1st two MCP joints Can lead to hypogonadism and hypothyroidism Can lead to hypogonadism Most individuals with hemochromatosis develop only one or a few of the above problems, with liver involvement being the most common. Significant end-organ damage is rare with a ferritin under 1000 ug/l. The blood (CBC) is normal in genetic hemochromatosis.

4 PRACTICE POINT With the exception of the skin discoloration, ALL of the problems above have many other and more common causes. In most cases, end-organ damage due to hemochromatosis cannot be differentiated from end-organ damage due to other causes Screening PRACTICE POINT The best screening test is percent iron saturation, done in the fasting state An iron saturation > 55% is suspicious for genetic hemochromatosis Measurement of ferritin alone is NOT adequate as ferritin is an acute phase reactant which can be elevated in acute and chronic infection, inflammation and neoplasm

5 Genetic Testing The test is for mutations in the HFE gene - C282Y and H63D (or S65C). End-organ symptoms are most common in patients with C282Y/C282Y; less common in patients with C282Y/H63D; and rare in patients with H63D/H63D. Risks for End-Organ Disease Depends on the amount of iron in the diet Less likely if there is regular blood loss menstruation, child-bearing, regular blood donation More likely if there are other insults to target organ e.g. combination of overuse of EtOH or chronic viral hepatitis and genetic hemochromatosis Possible other genetic factors beyond our ability to identify

6 Genetic tests Order on the Molecular Diagnostic Laboratory Requisition for Edmonton or Calgary. The test takes 2 to 4 weeks and costs $ It is covered by Alberta Health Care. Basic genetic information should be outlined by the family physician prior to genetic testing. The potential for insurance discrimination for asymptomatic patients should be considered. Further counselling is available through Medical Genetics Clinics in Edmonton or Calgary, if necessary Management Ferritin should be lowered to <50ug/L in patients with evidence of end-organ damage. For patients without evidence of end -organ damage ferritin should be lowered to <200 ug/l for women and <300 ug/l for men. Frequency of phlebotomy will depend on level of ferritin, always maintaining hemoglobin

7 above 110g/L. Regular blood donation is encouraged, if the patient is not otherwise unsuitable as a blood donor. Hemochromatosis is NOT transmissible through a blood donation. The patient should also reduce iron in the diet including reducing iron-rich foods, vitamin supplements with iron and use of uncoated iron cooking pots. For more information Edmonton Medical Genetics Clinic Calgary Medical Genetics Clinic Specialist hematologists/hepatologists Edmonton and Calgary Canadian Hemochromatosis Society

8 Algorithm for Clinical Suspicion of HFE Hemochromatosis