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Hemochromatosis
Abstracted from NEJM 350;23:2383-2397, 2004.
Symptoms
In adults fatigue, malaise, arthralgia, bronze
skin color, impotence, heart failure symptoms, diabetes symptoms are possible
presentations. In adolescents or young adults hypogonadotropic
hypogonadism and heart failure are common presentations
Exam
Hepatomegaly,
bronze skin, sequelae of associated conditions below
Laboratory
Increasing transferrin saturation level is the
earliest finding, elevated ferritin levels (>1000 may indicate
cirrhosis in C282Y homozygotes), mild transaminase elevations.
Associated Conditions
Cirrhosis, hepatocellular carcinoma, diabetes,
hypogonadotropic hypogonadism, hypothyroidism, cardiac arrhythmias, heart
failure, destructive arthritis.
Differential Diagnostic Considerations
Alcohol intake
Ferroportin-associated iron overload- hereditary autosomal dominant
hyperferritinemia, abnormal sequestration of iron by reticuloendothelial
system causing diminished iron in plasma with low transferrin saturation. The
ferritin will remain high despite phlebotomy. Aggressive phlebotomy will
cause anemia.
Aceruloplasminemia- loss of plasma
ferroxidase activity which impairs iron efflux from cells causing iron to
accumulate in various tissues especially brain and to a lesser degree liver.
Atransferrinemia or hypotransferrinemia-
impairs iron transport and delivery to the bone marrow, which results in
compensatory increased iron absorption with tissue deposition.
H Ferritin- not much known yet.
Genetics
HFE gene mutation: Autosomal recessive,
C282Y, chromosome 6, European descent of Celtic origin, homozygosity for it
occurs in 5/1000 people of northern European descent, penetrance is not always
complete. Adult onset with gradual iron loading over time.
Transferrin Receptor 2 mutation: Similar
to HFE in presentation. Adult onset with gradual iron loading over time.
Hemojuvelin gene mutation: Autosomal
recessive, iron loading worse earlier in life by the 2nd decade in both sexes,
more rapid iron accumulation than adult forms, associated conditions are more
evident in this form
HAMP (Hepcidin) gene mutation: Rare,
autosomal recessive
Diagnostic Studies
Transferrin saturation: >50%
Ferritin: over 400
Liver biopsy: hepatic iron index=hepatic [iron conc in mmoles/gr of liver(dry
weight)]/patient's age in years, abnormal is >1.9, normal is <1.0
Gene typing
Treatment
Phlebotomy: remove 1-2 units of blood per week
until serum ferritin is <50 ng/ml and transferrin saturation is
<30%. This may take 2-3 years to accomplish. It should be
followed maintenance phlebotomy to keep the levels down <50% on transferrin
saturation and <100 ng/ml for the ferritin level.
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