Prevalence of β-thalassemia minor in Poland

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Probl Hig Epidemiol 2009, 90(3): 322-324
Prevalence of b-thalassemia minor in Poland
Prewalencja b-talasemii minor w Polsce
Jerzy Kościelak
Profesor emerytowany, poprzednio w Instytucie Hematologii i Transfuzjologii, Warszawa, Polska
Introduction. The prevalence of b-thalassemia in Poland is unknown at
present, although hundreds of cases have been found and diagnosed.
Wstęp. W Polsce prewalencja b-talasemii jest nieznana, chociaż znaleziono
i rozpoznano setki przypadków tej choroby.
Objectives. The study aimed to estimate the prevalence of b-thalassemia
minor in Poland, without the time-consuming and expensive task of
assessing several thousands of randomly selected individuals.
Cele. Określenie prewalencji b-talasemii minor w Polsce, z pominięciem
czasochłonnego i kosztownego przebadania kilku tysięcy losowo wybranych
osobników.
Patients and methods. An upper, theoretical level of the disease prevalence
was calculated from the ratio of three cases with genetic b‑thalassemia
intermedia to 428 of those with b-thalassemia minor, selected from a group
of 432 indigenous patients with b-thalassemia. According to the population
genetics the ratio should be broadly proportional to the probability ratio
of conception of an offspring with b-thalassemia intermedia to the one
with b-thalassemia minor.
Pacjenci i metody. Obliczono górny, teoretyczny próg prewalencji
b‑talasemii minor ze stosunku trzech przypadków genetycznej b-talasemii
intermedia do 428 przypadków talasemii minor wybranych spośród 432
autochtonicznych chorych. Zgodnie z genetyką populacyjną stosunek ten
powinien być proporcjonalny do stosunku prawdopodobieństwa poczęcia
potomstwa chorego na b-talasemię intermedia do prawdopodobieństwa
poczęcia potomstwa chorego na postać minor.
Results. The calculated upper level of prevalence of b-thalassemia minor
amounted to 1.4%. This high prevalence was not confirmed during the
b-thalassemia examination of 700 patients of an outpatient clinic.
Wyniki. Obliczony górny próg prewalencji b-talasemii minor wyniósł 1,4%.
Tej wysokiej prewalencji nie potwierdzono po zbadaniu 700 pacjentów
przychodni lekarskiej.
Conclusions. The prevalence of b-thalassemia minor in Poland is lower
than 1.4%. This finding may be of value for the Polish Public Health
Authorities.
Wniosek. Prewalencja b-talasemii w Polsce jest niższa niż 1,4%. Wynik ten
może być przydatny instytucjom odpowiedzialnym za zdrowie publiczne
w Polsce.
Key words: b-thalassemia, prevalence
Słowa kluczowe: b-talasemia, prewalencja
© Probl Hig Epidemiol 2009, 90(3): 322-324
Adres do korespondencji / Address for correspondence
www.phie.pl
Nadesłano: 14.07.2009
Zakwalifikowano do druku: 26.09.2009
Introduction
b-Thalassemia minor is a rare disease in native
populations of central and northern Europe [1].
Therefore, its prevalence in the countries of these
regions is either unknown or has often been estimated
with a large margin of tolerance, e.g. below 0.5% for
England. By contrast, in the Mediterranean regions
of southern Europe, the b-thalassemia prevalence
may be as high as 20-30%. With a few exceptions the
disease is inherited in an autosomal recessive fashion
and is monogenic. The b-thalassemia severity depends
on the hetero- or homozygosity status of the affected
subjects and on the nature of the mutation. The b0
mutations show a complete abrogation of the b-globin
synthesis, whereas in the b+ mutations the synthesis is
only diminished. In the heterozygous form the disease
Prof. dr hab. med. Jerzy Kościelak
ul. Rajska 1 m 68, 02-654 Warszawa
tel. 022 49 310 51, e-mail: [email protected]
confers a degree of protection against malaria and, apart
from mild anemia, is otherwise innocuous. However,
it has been reported to be a risk factor for asthma [2]
and mood disorders [3]. Subjects with thalassemia
major are homozygous for the b0 mutations. They die
at an early age unless treated with blood transfusions
for life. The course of thalassemia intermedia is milder,
although patients may occasionally need transfusions.
Without a transfusion, the hemoglobin concentration
is usually maintained within the range of 6 to 9 g%.
Genotypically, patients with thalassemia intermedia
have identical or different thalassemic alleles, provided
that at least one of them is of the b+ category. Patients
with different thalassemic alleles are known as
compound heterozygotes.
In Poland, in spite of the two cases of b-thalassemia
in an ethnic Polish family described in 1961 [4], the
Kościelak J. Prevalence of b-thalassemia minor in Poland
disease was considered to be almost non-existent.
The first report of a large sample of 107 cases of
b‑thalassemia minor in indigenous Polish population
was published in 2006 [5], only after a countrywide diagnostic laboratory for hereditary anemias
was established at the Institute of Hematology
and Transfusion Medicine. The prevalence of
b‑thalassemia minor in Poland has been predicted
by us to be approximately 0.2%. There are, however,
reasons to assume that it might be higher, since in the
past a considerable area of Poland was covered with
marshes (the Polesie region, Byelorussia at present)
with endemic malaria. Thus, the knowledge of the
thalassemia prevalence in Poland should be of interest
for the Polish Public Health Authorities.
Yet this would be a time-consuming and expensive
task, in view of an expected low prevalence of
the disease and the necessity of screening several
thousands of randomly selected subjects. Therefore,
it seemed obvious to use our database to calculate the
prevalence of thalassemia minor.
Patients and Methods
In the years 2003-2008 we collected a database of
448 cases of b-thalassemia including 432 of indigenous
ones. In 216 patients, the diagnosis was confirmed by
genetic analysis. Among them there were 173 patients
with b-thalassemia minor of the Mediterranean type
mutations. Twenty out of 432 patients had low Hb
(<8.9 g%). This selected group included 6 males and
14 females (all unrelated), aged 1-80 years (mean
24 years) with Hb 6.4-8.9g % (mean 8.2g%); HbA2
4.4-6.5% (mean 5.4%), MCV 51.7-72.0 fL (mean
54.9 fL) and MCH 13.9-23.1 pg (mean 19.8 pg).
All 20 patients were initially considered to be either
compound heterozygotes or homozygotes but genetic
analysis confirmed this only in four patients (two
homozygotes and two compound heterozygotes).
One homozygous patient was not included in the
sample under study having been already diagnosed in
1974, although the diagnosis had been subsequently
changed and thereafter reestablished [6]. Of the
remaining three cases two were published [7, 8] and
one (a compound heterozygote) awaits publication
[Gruchota, Kościelak, in preparation].
Results and Discussion
The determination of prevalence requires
a random collection of samples, whereas in this study
they were selected. Assuming that thalassemic genes
have reached the Hardy-Weinberg equilibrium in the
Polish population, the problem can be obviated through
calculation of the prevalence of thalassemia minor
from the ratio of patients with genetic b-thalassemia
intermedia to those with the heterogenous, minor
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form. According to the population genetics the ratio
should be broadly proportional to the probability
ratio of conceiving a homozygous and a compound
heterozygous offspring with b-thalassemia intermedia
to that of a heterozygous offspring with b-thalassemia
minor in any sample of patients, provided that the
patients with b-thalassemia intermedia would not
be overrepresented in the sample. This might well
occur since the clinically more severe thalassemia
intermedia is likely to attract more attention of the
medical personnel. Yet we founded our database at
the time when the presence of thalassemia in Poland
was a novelty, and, for the diagnosis confirmation, we
would receive blood samples from all over Poland and
from all patients suspected of thalassemia, irrespective
of the disease severity. Nevertheless, the prevalence
calculated by this method may be overestimated and
indicate rather a theoretical upper level of prevalence
instead of its true value. In spite of this imprecision,
the calculation of prevalence from the probability
ratio may be of certain significance in the situation
when randomly collected samples are unavailable.
Such calculation is allowed only at low b-thalassemia
prevalence, as in Poland, when the probability of
mating of a homozygous with a homozygous or
a heterozygous individual is slim.
The prevalence of thalassemia minor (p) can
be calculated as follows: if ntma is the number of
homozygous + compound heterozygous patients
with b-thalassemia intermedia, ntmi, the number of
heterozygous patients with b-thalassemia minor,
Ptma, the probability of conceiving a b-thalassemia
intermedia offspring from mating of two heterozygous
individuals, and Ptmi, the probability of conceiving
a heterozygous offspring (with b-thalassemia minor)
from mating a healthy subject with a heterozygous
one, then ntma : ntmi = Ptma : Ptmi. Since Ptma = p2 ×
0.25 and Ptmi = p × 0.5, the equation may be reduced
to ntma : ntmi = p × 0.5, i.e. p=2ntma : ntmi. Thus, the
calculated “theoretical” prevalence in our sample of
patients is 2× 3 : 428 = 0.014 (1.4%). The confidence
interval for the simple proportion of 3: 428 = 0.709%
was calculated by the Fisher Exact method employing
the OpenEpi calculator [9]. The interval was 0.145 –
2.035% at 0.95% of probability suggesting significance
of the proportion and ensuing prevalence. To check the
validity of the calculated prevalence of b-thalassemia
minor, a complete blood count of 700 subjects (aged
1-81 years, mean 47.6) from a non-public outpatient
analytical laboratory was examined. The initial criteria
for the selection of samples suspected of thalassemia
included MCV of 68 fL or less, MCH of 27 pg or less,
and RDW-CV of 14.9% or less. Subjects with red cell
indices within these limits were examined for HbA2
level. However, none thalassemic subject was found
324
after the examination of complete blood counts of
200 subjects. Thereafter, the criterion for MCV was
increased to 75 fL and further 500 individuals were
examined. In all, only one thalassemic subject with
MCV of 62.5 fL and HbA2 of 5.3% was found instead
of several expected. The subject was informed about
her condition but she was aware of it, having been
diagnosed with b-thalassemia when temporarily living
in England. Thus, the upper limit for the prevalence
of thalassemia minor in Poland is 1.4%.
Conclusion
The upper limit for the prevalence of thalassemia
minor in Poland, of 1.4%, is likely to be over-estimated
due to the reasons stated above. Nevertheless it
has to remain at that value until the prevalence
of b‑thalassemia in Poland is determined more
precisely.
Probl Hig Epidemiol 2009, 90(3): 322-324
Acknowledgements. The author thanks prof. Andrzej Zieliński
of the Department of Epidemiology, the National Institute of
Public Health, the State Institute of Hygiene, for valuable
comments, dr Paweł Goryński of the Center for Monitoring and
Analyses of Population Health Status and Health Care System
of the same Institute for the advice on validity and the method
of determination of confidence interval for a simple proportion,
and Ms Urszula Mokras of the Department of Biochemistry
of the Institute of Hematology and Blood Transfusion for the
assistance in selection of patients for the present study.
The study was supported by the Ministry of Higher Education
and Science (Grant No. PBZ-KBN-122/P052004).
Podziękowania. Autor pragnie podziękować prof. Andrzejowi
Zielińskiemu z Zakładu Epidemiologii Narodowego Instytutu
Zdrowia Publicznego za cenne uwagi, dr Pawłowi Goryńskiemu
z Centrum Monitorowania i Analiz Stanu Zdrowia Ludności
tego samego Instytutu za radę na temat zasadności i sposobu
obliczenia przedziału ufności dla prostej proporcji i Pani Urszuli
Mokras z Zakładu Biochemii Instytutu Hematologii w Warszawie
za pomoc w selekcji pacjentów do niniejszej publikacji.
Praca była wykonana w ramach projektu zamawianego
Ministerstwa Nauki i Szkolnictwa Wyższego (Nr . PBZ-KBN122-P052004).
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