Portada Simposios - Supplements - Haematologica

XLII Reunión Nacional de la AEHH y XVI Congreso de la SETH. Simposios
267
blocks the glycosylation of glycoprotein acceptors
and shifts polylactosamines to lipid acceptors. Nevertheless,
the results of structural analysis of CDAII
band 3 carbohydrates suggested disruption of the
biosynthesis around the N-acetylglucosaminyltransferase
II (GnT-II) and a-mannosidase II (MII) steps. Linkage
analysis in our series of families excluded these
candidate genes 13 . More over a genome wide search
obtained conclusive evidence for linkage of CDA II to
microsatellite markers on the long arm of chromosome
20 (20q11.2). A maximum two-point lod score
of 5.4 at q = 0.00 with the marker D20S863 was obtained
14 .
The effects of reduced glycosylation on the functionality
of band 3 in CDA-II patients was analyzed. All
the CDA-II patients demonstrated a thinner band
3 than usual which also migrates slightly faster on
SDS-PAGE. Analysis of the anion transport (inhibition
of sulphate flux by H2-DIDS) demonstrated that
in the CDA-II erythrocytes there was a decrease in the
activity of the anion transport for band 3 molecule.
Furthermore the latter cells contain higher amounts
of aggregate band 3 than control eryhtrocytes 15 .
As aggregated band 3 was reported to bind naturally
occurring antibodies which are able to mediate
the phagocytic removal of red blood cells. These results
suggested that the mild hemolysis showed by
CDA-II patients may be ascribed to clusterization of
band 3 which leads to IgG binding and phagocytosis
and not to a secondary modification of the RBC cytoskeletal
structure. These data are consistent with
the possible beneficial of splenectomy in CDA-II patients,
also is some concerns are due to the possible
increase of iron overload in other tissues 15 .
Anemia is often first noted in infancy or childhood
and the degree varies widely, from mild to severe. In
some cases regular transfusions are required but it
is rare that the anemia is severe since birth. Mean
Hb level in a very large group of CDA-II patients is
99 g/L. This mean that anemia is usually very mild.
In some cases transfusion-deppendence could be generated
by the interaction with a different red blood
cell defect. It is interesting to note that three out
of these subjects were CDA-II and beta-thal heterozygote.
This observation could suggest that the inheritance
of a different red cell defect (also if this is
mild) could worsen the hematological status of
CDA-II and allow to the transfusion-dependence
(Iolascon, unpublished data).
Hemosiderosis is the most important long term
complication, except in those patients protected by
ongoing iron loss as menstruations, pregnancies or
hemosiderinuria. Furthermore gallstones formation,
which appear related to the ineffective eryhtropoiesis
and the the hemolytic component of this disease, is
the most prevalent complication.
Very recently a statistically significant correlation
between UGT1A (TA) 7 /(TA) 7 genotype, i.e., Gilbert,s
syndrome, and the increased rate of gallstones in
CDAII patients was demonstrated. The effects of Gilbert‘s
syndrome on bilirubin values and gallstone
formation are clearly visible comparing CDAII patients
with different UGT1A genotype belonging
from same families 16 .
Aknowledgements
The Author is particularly grateful to the Contributors
of the CDA Consortium. A special thanks to: Jean Delaunay,
Sunitha Wickramasinghe, Herman Heimpel, Hanna
Tamary and Anders Whalin.
This paper was supported by the MURST 40 % (Cofinanziamento),by
Telethon to A.I. (project E-645) and by
the University of Bari.
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