Portada Simposios - Supplements - Haematologica

266 Haematologica (ed. esp.), volumen 85, supl. 2, octubre 2000
syndactily. Eighty-five percent of the symptomatic
neonates required red blood cell transfusions, but
only up to the age of 3 months in most of them. She
suggested that the neonatal manifestations of CDA
type I vary in clinical severity from severe intrauterine
anemia with hydrops fetalis, to moderate intrauterine
anemia associated with low birth weight, neonatal
jaundice, hepatosplenomegaly and transient
cardiac abnormalities 5 .
The mean hemoglobin level in a group of adult patients
was 86 g/L; the MCV was high, with a mean
value of 101 fL. However in extented series a group
of transfusion-dependent patients until splenectomy
could be observed. The absolute reticulocyte counts
were within normal limits. Ferritin was moderately
elevated. Serum EPO levels were mildly elevated.
Bone marrow cultures revealed a 413 % increase in
marrow CFU-E, with BFU-E rising only to 163 %;
CFU-C growth was similar to that of the control. Cytofluorimetric
analysis shows a cell arrest in the
S-phase.
Diagnosis was confirmed in each patient by bone
marrow EM. The criteria for the diagnosis of CDA
type I include the demonstration of a characteristic
ultrastructural abnormality of the erythroblast heterochromatin
(a spongy or “Swiss-cheese” appearance)
in a high proportion of the erythroblasts. Another
striking abnormality is the invagination of the
nuclear membrane, carrying cytoplasm and cytoplasmic
organelles into the nucleus.
By means of a genome wide search in a group of
bedouin consanguineous families Tamary et al. localized
the gene for CDA type I to a 0.5 cM region on
chromsome 15q15.1-15.3. Haplotype analysis pointed
to a single founder mutation for most of the carrier
haplotypes 6 .
CDA-III
CDA type III was first described by Wolff & von
Hofe in 1951 7 , later Bergström and Jacobsson reported
the Swedish CDA-III family which is at focus
of the present report 8 . Thirty-four patients have been
diagnosed in the Swedish family.
The clinical picture is characterized by symptoms
of mild or moderate hemolytic anemia with fatigue,
weakness, biliary symptoms and jaundice. Most patients
have mild anemia characterized by jaundice
and some episodes of abdominal pain and dark urine.
The low-grade severity of the disease does not
change over the years, although the anemia may
constitute a problem in some patients with concomitant
red blood cell disorders. There is no iron overload
and serum thymidine kinase is high. Estimation
of serum thymidine kinase may be used in family studies
for discrimination between healthy siblings and
affected individuals in situations when bone marrow
examination is not suitable 9 . Monoclonal gammopathy
of undetermined significance and multiple
myeloma was described in several patients.
Red blood cell count and blood smear examination
show macrocytosis (median MCV 96 fL) poikilocytosis
and anisocytosis. Some extremely large oval
erythrocytes can usually be observed in the smear.
Bone marrow smears show hyperplasia of the erythropoiesis
and numerous multinucleate large erythroblasts,
sometimes containing up to twelve nuclei,
characteristic for this disorder. The size and appearance
of the nuclei may vary within the same cell.
Granulocyte precursors and megakaryocytes show
normal morphology. Electron microscopy reveals disorganised
erythroblast nuclei with different appearances
within the same cell, intranuclear clefts, and
intracytoplasmatic inclusions 10 .
CDA-II
CDA II is the most common form of the congenital
dyserythropoietic anemias. The geographic distribution
of affected patients suggests a higher frequency of
the gene in northwest Europe, in Italy and in the Mediterranean
countries. If we look at the epidemiology
of CDA-II it is very difficult to assess it; however the
vast majority of CDA-II are signalled in southern Europe
or in the southern europe ancestry. Up to now it is
difficult to assess if this is due to a very clustered distribution
or if it is a bias due to the hematologists 1,11 .
Some years ago the first International Registry on
CDA-II was established. This registry allows to epidemiology,
clinical and molecular studies. Up to
april 2000 58 italian patients coming from 45 families
and 38 not-italian patients from 33 families were
recruited. The overall of the enrolled population was
96 patients from 78 families 11 .
Looking at the regional distribution of the italian
patients we could observe that the vast majority of
the ancestry of these patients are from southern
Italy. Hence there is a clusterization of the cases all
coming from southern Italy this could suggest a
founder effect. However molecular studies by means
of microsatellites localized where the gene was mapped
failed to demonstrate the existence of a common
haplotype 11 .
Main clinical findings of CDA-II are anemia, jaundice
and variable splenomegaly. These are the same
of hereditary spherocytosis and it is possible to make
confusion between these conditions. Mainly because
the osmotic fragility test gave the same result in
these conditions.
CDAII patients suffer from a life-long anemia. It
results from a combination of the death of erythroblasts
in the bone marrow (ineffective erythropoiesis)
and an increased breakdown of released red cells
(peripheral haemolysis). CDA II is associated with a
well defined cellular and ultrastructural phenotype:
bi- or multinucleated late precursors and flat vesicles
of variable length 1 .
The principal biochemical feature is the hypoglycosilation
of some proteins (such as transferrin and
band 3) 12 . It appears that a genetic factor in CDAII