|
Common autosomal recessive disorder affecting approximately 1 million people in the United States.
The affected gene, hfe, encodes an atypical member of the class I major histocompatibility protein family that heterodimerizes with the beta-2 microglobulin.
Most affected patients are homozygous for C282Y (C-cysteine, Y-tyrosine)
C282Y mutation may cause disrution of an intramolecular disulfide bond and may interfere with beta-2 microglobulin bonding. Mice deficient in beta-2 microglobulin & mice deficient in hfe both develop systemic iron overload.
Prognosis & Survival
Without phlebotomy- 18 months according to a study of 111 individuals with hemochromatosis, 26 of which did not undergo phlebotomy.
With phlebotomy- 63 months according to the above population study.
Symptoms:
1. ARTHRITIS can improve after phlebotomy
2. Diabetes Mellitus
3. Hypogonadism
4. Hypopituitarism
5. Hepatic Failure
6. Hepatocelluar carcinoma
7. Heart Failure - cardiac symptoms can improve following vigorous phlebotomy & CHF treatments
8. Infections- Vibrio vulnificus, Yersinia enterocolitica.
Avoid raw shellfish (source of Vibrio vulnificus)
Diagnosis
1. TRANSFERRIN saturation greater than 62% in male or greater than 50% in female.
(note that transferrin saturation increases before excess iron accumulates!)
2. Serum ferritin level greater than 325 ng/ml in males & greater than 125 ng/ml in females supports the diagnosis.
3. Liver Biopsy
4. C282Y Mutation
5. H63D Mutation
Therapy
1. PHLEBOTOMY
The goal is to make the patient iron deficient. Iron depletion in indicated by the development of anemia i.e. HCT 30 & MCV of 75 fL or less. Serum ferritin levels will be down to 25 ng/ml.
Each 500 ml whole blood removed from an individual with HCT=40 contains 200 mg Iron (1 mg iron/1 ml RBC).
> PHASE I: Rapid Sequence Phase
Remove 500 ml blood Q week.
> PHASE II: Maintenance Phase
Remove 500 ml blood every 2-6 months with the goal to attain a ferritin concentration level of approximately 50 gL & normal HCT.
2. IRON CHELATION
Only for use in patients with iron overload secondary to frequent blood transfusions. It is inefficient in removing body storage iron in hemochromatosis. However, it may be used in patients with poor venous access or marked anemia, etc. |
 |
|
| | | |
|
Diet Dietary factors may influence the phenotypic expression of hemochromatosis.
1. Patients should not consume foods that contain large concentrations of bioavailable iron. This includes red meats.
2. Items in foods & drinks, such as tannates in tea, oxalates, phytates, calcium & phosphates, can bind iron & inhibit its absorption.
3. Patients should not use iron supplements. This includes mutlivitamin preparations that contain iron.
4. Alcohol could increase iron absorption.
5. Certain alcoholic beverages, such as red wine, contain a high concentrations of iron.
6. Intake of 30 grams or more of alcohol daily potentiates hepatic injury due to iron overload and increases the relative risk for primary liver cancer in persons with cirrhosis.
7. Vitamin C increases intestinal absorption of inorganic iron. However, patients should not be discouraged from eating fresh fruits & vegetables containing vitamin C. It is recommended to limit the intake of vitamin C in supplements to 500 mg/d.
8. Occasionally, raw or improperly cooked shellfish is contaminated with V. vulnificus & can cause sepsis in patients with iron overload states. Likewise, seafood from potentially contaminated waters should be thoroughly cooked.
|
|
|
|
