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In response to the posting by "watchman": yes, there is a possible
connection between iron overload and Fanconi anemia.
Common wisdom in the early twenties had it that anemia was caused by
iron deficiency. Hence, the young pediatrician Guido Fanconi in
Zuerich (Switzerland) treated three of this patients with a novel kind
of therapy, now known as "blood transfusion". His patients died soon
and precipitously. Post mortems revealed hemosiderosis (deposits of
iron in the liver). Looking at blood smears Fanconi concluded that
his patients had a "pernicious" anemia. Decades later we learned
that "pernicious anemia" is caused by defects in folic acid uptake
and metabolism. Anyway, Fanconi correctly concluded that he
witnessed a novel disease entity. Later, chromosomal instability
was found. The disease follows autosomal recessive inheritance; to
date, 5 complementation groups have been found. The gene for one
group has been isolated (M. Buchwald and coworkers, HSC, Toronto,
Ontario, Canada). Several groups are very close to a second gene.
In a paper earlier this year we have described an increased
sensitivity of lymphoblastoid cell lines from Fanconi anemia
patients (Poot et al., Exp. Cell Research 222, 262-268, 1996).
We have "cured" the cell cycle defect of these cells by culture in
the presence of an iron chelator and, conversely, aggreviated the
situation by supplementing the cultures with excess iron.
Apparently, oxygen interacted with iron to cause this cytotoxic
effect. This result nicely corroborated earlier work of Schindler
and Hoehn (1988) Am. J. Human Genet. 43, 429-435.
Fanconi anemia is a terrible, though fascinating, genetic disease.
I am sure that there will be a lot of debate on it during the next
annual meetings of the American Societies of Hematology and Human
Genetics.
Martin Poot
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