2 research outputs found
Pure red cell aplasia in swedish children : Clinical features, epidemiological and etiological aspects of transient erythroblastopenia of childhood and Diamond-Blackfan anemia
Background: Anemia due to impaired erythropoiesis is a rare condition
that is more common in children than in adults. Pure red cell aplasia
(PRCA) is the term used to denote anemia due to failure of the bone
marrow that affects only the erythropoietic cell line. PRCA exists in two
forms only presented in children. One is a usually chronic, congenital
disorder called congenital hypoplastic anemia or Diamond-Blackfan anemia
(DBA), while the other is an acquired, transient condition called
transient crythroblastopenia of childhood (TEC).
DBA is a macrocytic anemia, the severity of which can be either mild or
serious. It is usually diagnosed in early infancy, and its
pathophysiological mechanism is not yet known. Congenital malformations
are seen in about 40% of the cases and there is evidence both of
autosomal dominant and of recessive inheritance of the disease, although
most cases are sporadic. About 50% respond to cortisone, while the rest
depend on erythrocyte transfusions, which in the long-term will lead to
iron overload and consequently a risk for hemosiderosis and organ
dysfunction.
TEC was described as a distinct entity in 1970. It is an acquired
self-limited disorder of unknown etiology and pathophysiology, affecting
otherwise healthy young children, usually six months to four years of
age. The disease presents with a significant normocytic anemia and
reticulocytopenia due to reduced erythropoiesis in bone marrow.
Spontaneous recovery within a few weeks from diagnosis is usual and the
disease does not recur.
Objectives and methods: The objectives of the work presented in this
thesis were to estimate the incidences of TEC and DBA, to describe the
common pattern of TEC and DBA in Sweden, to study some specific viruses
as possible causes of TEC, to study the treatment and outcome of patients
with DBA, and to identify possible prognostic features of DBA.
Information on patients with TEC and DBA, respectively, was collected
from all pediatric departments in Sweden in two different population-
based surveys. Specimens were obtained for viral diagnostics in a third
prospective study of 10 patients with TEC from five Swedish pediatric
departments.
Materials, results and conclusions: TEC was diagnosed in 53 cases during
the years 1987 to 1989 in children less than 10 years of age. Almost all
(51/53) were less than 3 years of age. In this group, the incidence was
4.3/105/year, which means 15-20 cases per year in Sweden. A meta-analysis
showed that data from the present study were comparable to those
previously reported. There were four pairs of siblings, including one
pair of identical female twins among these children. This is a much
higher familial occurrence than expected. The probability of finding 4
pairs of siblings with this disease in 50 families is less than one in a
million, if the disease does not contain a hereditary component. The
findings indicate that TEC involves hereditary factors, and they suggest
that inheritance is autosomal dominant (Papers 1 and 11).
During the years 1994 to 1998, 10 consecutive cases of TEC were
prospectively included in a study of etiological aspects of the disease,
with special reference to human parvovirus B 19 (B 19), human herpesvirus
6 (F1HV-6), cytomegalovirus (CMV) and Epstein-Barr virus (EBV). An acute
EBV infection was revealed in one child, but no other IgM positivity was
found at presentation. Some cases were IgG positive at presentation
(HHV-6 (2 cases), EBV (1 case) and CWV (1 case)), but it was not possible
to determine in any of these cases when the child had been infected. No
child gave positive results for B 19 or HEIV-6 from PCR performed on sera
and bone marrow collected at presentation. Cultures for virus on bone
marrow, stools, and aspirates from the nasopharynx were negative in all
cases but one, who showed rotavirus in stool. These results suggest that
neither HHV-6, B 19, EBV, nor CMV is a single causative agent of TEC
(Paper Ill).
Finally, all cases with DBA diagnosed in children born in Sweden 1980 to
1997 were identified. Twenty patients (10 boys and 10 girls) were
included, and the incidence was calculated to be 10.6/106 live births,
which is twice the incidence reported from England in 1996. A balanced
reciprocal X;19 translocation was identified in one child. This suggested
that DBA is linked to the 19q-chromosome region. This linkage was later
confirmed by others in 25% of DBA-cases and it has recently been shown
that at least 3 different genes, one of which has been identified, can
independently be responsible for DBA when mutated. The clinical course
and the treatment of DBA were the same as those reported in the
literature. No prognostic factors could be identified. The final outcome
was 55% transfusion-dependent children, one of whom subsequently
underwent a successful bone marrow transplant. All transfusion-dependent
patients were also treated with desferrioxamine in order to reduce iron
overload. The compliance is high, but iron-overload, with its risk for
related complications, is seen despite regular chelation therapy. (Papers
IV and V)