Hemochromatosis diagnosis 
Hemochromatosis is the term used to describe a number of hereditary conditions which all are characterized by iron overload, increased gastrointestinal absorption and tissue deposition or iron. This is the most common genetic disorder in those of European ancestry and is autosomal recessive in inheritance.
Symptoms of Hemochromatosis (1 or more of following):
- Abdominal pain
- Amenorrhea
- Apathy
- Arthralgia
- Cardiomyopathy
- Congestive heart failure (Cardiomegaly)
- Diabetes
- Fatigue
- Hepatomegaly
- Hyperpigmentation of the skin
- Hypogonadism
- Hypothyroidism
- Impotence
- Lethargy/Malaise
- Liver function test elevation
- Weight loss
- Type I: Presence of the HFE gene is the most common form of hemochromatosis (>90% of cases) and 1 of every 200-400 northern Europeans are homozygous for this mutation in the HFE gene (only occurs in Caucasians)
- Type II: Juvenile hemochromatosis results from a mutation in the hemojuvelin or hepcidin gene
- Type III: Transferrin receptor 2 hemochromatosis results from a mutation in the transferrin receptor gene
- Type IV: Ferroportin disease results from a mutation in the ferroportin gene
- Type V: Other types of hemochromatosis that are rare such as mutation in the ceruloplasmin, transferrin or divalent metal transporter genes
In diagnosing hemochromatosis based upon iron overload/serum ferritin levels; consideration of other conditions that may cause this may need to be evaluated:
- Alcoholic liver disease
- Hepatitis B
- Hepatitis C
- Fatty liver
- Porphyria cutanea tarda
- Transfusion related iron overload
- Transferrin saturation is the best screening method
- Conventional Units = [Serum Fe (µg/dL)/TIBC (µg/dL)]* 100%
- SI Units = 3.982 x Serum Fe (µmol/L)/Transferrin (g/L)
- Normal Female transferrin saturation=<45%
- Normal Male transferrin saturation=<50%
- Patients heterozygous for HFE usually have transferrin saturation 45-62%
- Patients homozygous for HFE usually have transferrin saturation of 70-100% (but may have levels lower that overlap with heterozygous levels)
- Ferritin levels and serum iron levels are usually elevated in hemochromatosis, but this is not specific as multiple other conditions may cause this:
- Ferritin levels to make diagnosis:
- Ferritin>400 ng/mL (>400 µg/L) in men and post-menopausal women suggests hemochromatosis
- Ferritin>200 ng/mL (>200 µg/L)in pre-menopausal women suggests hemochromatosis
- Ferritin level as relates to degree of iron excess
- Ferritin level 400-500 ng/mL (400-500 µg/L) = mild excess of iron
- Ferritin level 500-1000 ng/mL (500-1000 µg/L)= moderate excess of iron
- Ferritin level >1000 ng/mL (>1000 µg/L) = severe excess of iron
- Gene testing considered in limited cases for the HFE gene (>90% of cases)
- Liver biopsy (rarely indicated and mostly replaced by genetic testing)
- Liver MRI (Can estimate total hepatic iron using 1.5T magnet and appropriate algorithm software)
Diagnosis (Specific Algorithm):
Step A: Transferrin Saturation
- >50% (Female)
- >60% (Male)
Step B: If elevated in step A, retest after overnight fast, if still elevated, look at serum ferritin
Step C: If serum Ferritin elevated, the diagnosis is very likely
- Ferritin>400 ng/mL (µg/L) in men and post-menopausal women suggests hemochromatosis
- Ferritin>200 ng/mL (µg/L) in pre-menopausal women suggests hemochromatosis
Step D: Consider liver biopsy or genetic testing or Liver MRI for confirmation
Note: If serum transferrin and ferritin levels are not definitely elevated when measured; it is unlikely that hereditary hemochromatosis is present.
When this diagnosis is made a diet devoid of iron, vitamin C and ethanol should be recommended.
- Type I, II and III:
- When serum ferritin is >400 ng/mL (males/post-menopausal females) or >200 ng/mL (pre-menopausal females), phlebotomy at 7 mL/kg weight based should be instituted
- This should be done repetitively weekly until serum ferritin =<50 ng/mL (monitor for anemia)
- Thereafter, every 4-6 months phlebotomy is often indicated with careful monitoring to keep serum ferritin of =<50 ng/mL
- Type IV:
- May not tolerate phlebotomy due to developing anemia (may require chelation)
- Type V:
- Typically will develop anemia and require chelation (e.g. desferoxamine)
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