Bases moleculares de alfa-talasemia en la Argentina

La α-talasemia, es uno de los desórdenes hereditarios más frecuentes mundialmente. Al presente, el diagnóstico molecular es la única herramienta que permite el diagnóstico certero. El propósito de este trabajo fue caracterizar las bases moleculares de estos síndromes en nuestro medio, y establecer relaciones genotipo-fenotipo. Mediante la complementación de distintas técnicas de biología molecular e hibridación fluorescente in situ (FISH), se logró poner en evidencia la presencia de mutaciones α-talasémicas en 145 de 184 (78.8%) pacientes estudiados con perfil hematológico compatible con α-talasemia. Dentro de este grupo, las deleciones correspondieron al defecto genético más frecuente, prevaleciendo la mutación -α3.7 en genotipos heterocigotas y homocigotas. Asimismo, en pacientes con fenotipo α0 las deleciones prevalentes fueron -MED y -CAL/CAMP. Este estudio permitió también describir una deleción de la región sub-telomérica en un paciente con α-talasemia y retraso mental. En el 7.6% de los pacientes caracterizados clínicamente como posibles α-talasémicos (microcitosis con valores de Hb A2 inferiores al 3.5%), se hallaron mutaciones β-talasémicas en estado heterocigota. Se lograron establecer perfiles hematológicos asociados a los genotipos α+ y α0 para pacientes adultos y niños. Esperamos que este trabajo pueda servir como guía para reconocer posibles portadores α-talasémicos. También permite destacar el trabajo en conjunto de médicos hematólogos, el laboratorio (bioquímico y de biología molecular) y de los médicos genetistas, con el fin de proporcionar adecuado consejo genético.

The α-thalassemia is one of the most common hereditary disorders worldwide. Currently, molecular diagnostics is the only available tool to achieve an accurate diagnosis. The purpose of this study was to characterize the molecular bases of these syndromes in our environment and to establish genotype-phenotype associations. Through a combination of different molecular techniques and fluorescent in situ hybridization (FISH),we were able to find α-thalassemic mutations in 145 of the 184 patients (78.8%) studied with hematological parameters compatible with α-thalassemia. Deletions of the a-globin genes resulted the major molecular cause of the disease, and the most frequent mutation was -α3.7, found in homozygous and heterozygous genotypes. In patients with α0 phenotypes, other prevalent mutations were -MED and -CAL/CAMP. The description of a sub-telomeric deletion in a patient with α-thalassemia and mental retardation was also achieved. β-thalassemic mutations in heterozygous state were found in 7.6% of the patients, who presented α-thalassemic clinical features (microcytosis and Hb A2 levels below 3.5%). Hematologic profiles for the α+ and α0 genotypes were established for adult and pediatric patients. Hopefully, this work will provide guidelines for the detection of possible α-thalassemic carriers. It also highlights the collaborative work of hematologists, the biochemical and molecular biology laboratory and genetists, in order to provide appropriate genetic counseling.

Survival and mortality among users and non-users of hydroxyurea with sickle cell disease / Sobrevida e mortalidade em usuários e não usuários de hidroxiureia com doença falciforme / Sobrevida y mortalidad en usuarios y no usuarios de hidroxiurea con enfermedad falciforme

OBJECTIVE: to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease. METHOD: cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05. RESULTS: of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause. CONCLUSION: the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions. .

OBJETIVO: estimar a sobrevida, mortalidade e causa de morte em usuários ou não de hidroxiureia com doença falciforme. MÉTODO: coorte retrospectiva de 1980 a 2010, de pacientes internados em dois hospitais públicos brasileiros. Determinou-se a probabilidade de sobrevida com Kaplan-Meier, cálculos de sobrevida (SPSS versão 10.0), comparação entre curvas de sobrevida e método Log Rank. Nível de significância p=0,05. RESULTADOS: de 63 pacientes, 87% estavam com anemia falciforme, sendo 39 em uso de hidroxiureia, com média de idade na instituição do fármaco de 20,0±10,0 anos e dosagem média de 17,37±5,4 a 20,94±7,2mg/kg/dia, elevando a hemoglobina fetal. Na comparação de usuários e não usuários de hidroxiureia, a curva de sobrevida foi maior nos usuários (p=0,014). Ocorreram 10 óbitos, com idade média de 28,1 anos, tendo como causa principal a Insuficiência Respiratória Aguda. CONCLUSÃO: a curva de sobrevida é maior nos usuários de hidroxiureia. Os resultados apontam a importância do enfermeiro incorporar avanços terapêuticos da hidroxiureia em suas ações assistenciais. .

OBJETIVO: estimar la sobrevida, la mortalidad y la causa de muerte de usuarios y no usuarios de hidroxiurea con enfermedad falciforme. MÉTODO: cohorte retrospectiva de 1980 a 2010 de pacientes internados en dos hospitales públicos brasileños. Se determinó la probabilidad de sobrevida con Kaplan-Meier, cálculos de sobrevida (SPSS versión 10.0), comparación entre curvas de sobrevida, método Log Rank. Nivel de significado p=0,05. RESULTADOS: de 63 pacientes, 87% estaban con anemia falciforme, siendo que 39 usaban hidroxiurea, promedio de edad en la institución del fármaco de 20,0±10,0 años y dosificación promedio de 17,37±5,4 a 20,94±7,2mg/kg/día, elevando la hemoglobina fetal. En la comparación de usuarios y no usuarios de hidroxiurea, la curva de sobrevida fue mayor en los usuarios (p=0,014). Ocurrieron 10 muertes, edad promedio de 28,1 años, siendo la Insuficiencia Respiratoria Aguda la causa principal. CONCLUSIÓN: la curva de sobrevida es mayor en los usuarios de hidroxiurea. Los resultados apuntan la importancia de que el enfermero incorpore los avances terapéuticos de la hidroxiurea en sus acciones asistenciales. .

Haemoglobinopathies in Southeast Asia.

In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous α-thalassaemia 1), homozygous β-thalassaemia, β-thalassaemia/Hb E and Hb H diseases. α-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the β-globin gene sequence are the major molecular defects responsible for most β-thalassaemias. Clinical manifestations of α-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of β-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, β-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous β-thalassaemia. Concomitant inheritance of α-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both α- and β-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies.

The inherited disorders of haemoglobin: an increasingly neglected global health burden.

An estimated 300,000 babies are born each year with a severe inherited disease of haemoglobin and that over 80 per cent of these births occur in low- or middle-income countries. As these countries go through the epidemiological transition, characterized by a reduction in childhood and infant mortality due to improved public health measures, infants who had previously died of these conditions before they were recognised are now surviving to present for diagnosis and treatment. For a variety of reasons, even in the rich countries there are limited data about the true frequency, natural history, and survival of patients with these disorders, information that is absolutely critical towards providing governments and international health agencies with accurate information about the true global health burden of these conditions. The situation can only be improved by major action on the part of the rich countries together with the formation of partnerships between rich and poor countries and input from the major international health agencies and funding organisations.

A comparative study of hematological parameters of α and β thalassemias in a high prevalence zone: Saudi Arabia.

BACKGROUND AND AIMS: Saudi Arabia falls in the high prevalent zone of αα and β thalassemias. Early screening for the type of thalassemia is essential for further investigations and management. The study was carried out to differentiate the type of thalassemia based on red cell indices and other hematological parameters. MATERIALS AND METHODS: The study was carried out on 991 clinically suspected cases of thalassemias in Riyadh, Saudi Arabia. The hematological parameters were studied on Coulter STKS. Cellulose acetate hemoglobin electrophoresis and high-performance liquid chromatography (HPLC) were performed on all the blood samples. Gene deletion studies were carried out by restriction fragment length polymorphism (RFLP) technique using the restriction endonucleases Bam HI. STATISTICAL ANALYSIS: Statistical analysis was performed on SPSS 11.5 version. RESULTS: The hemoglobin electrophoresis and gene studies revealed that there were 406 (40.96%) and 59 (5.95 %) cases of β thalassemia trait and β thalassemia major respectively including adults and children. 426 cases of various deletion forms of α thalassemias were seen. Microcytosis was a common feature in β thalassemias trait and (-α/-α) and (--/αα) types of α thalassemias. MCH was a more significant distinguishing feature among thalassemias. β thalassemia major and α thalassemia (-α/αα) had almost normal hematological parameters. CONCLUSION: MCV and RBC counts are not statistically significant features for discriminating between α and β thalassemias. There is need for development of a discrimination index to differentiate between α and β thalassemias traits on the lines of discriminatory Indices available for distinguishing β thalassemias trait from iron deficiency anemia.

Hemoglobin D [Hb D Punjab/ Los Angeles and Hb D Iran] and Co-Inheritance with Alpha- and Beta- Thalassemia in southern Iran

Hemoglobin-D [Hb D] is an uncommon structural hemoglobin variant, which is reported to be prevalent in north western India. There are only a few small series, of this entity in the literature. We report the largest single center experience on this entity from Iran. Between November 2002 and December 2010 as a result of screening premaritally for betathalassemia in Shiraz, Fars Province, Southern Iran, column chromatography, Hb electrophoresis, solubility test, and/or high performance liquid chromatography [HPLC], direct sequencing and restriction analysis were used for hemoglobinopathies and structural Hb variants. The data of 220 subjects with Hb D variants are analyzed in this report. These comprised of 180 carries of Hb D; 92 cases of Hb D Punjab/Los Angeles [beta 121[Glutamic acid -> Glutamine]] and 88 subjects with Hb D Iran [beta 22 [Glu- > Gln]], 3 homozygous cases for Hb D, 17 subjects with betathalassemia- Hb D, 12 with Hb D- alpha- thalassemia- 1, 3 homozygous Hb D- alpha thalassemia- 1 trait, one with Hb D Punjab - sickle cell anemia, and two with Hb D Iran/sickle cell anemia. The carriers of Hb D and homozygous cases for Hb D were not anemic and had normal red blood cell morphology, as they are not usually detected. If Hb D was inherited in combination with thalassemia, the subjects had mild anemia and in some of them, the spleen was palpable [1-2 cm]. Co-inheritance of alpha thalassemia and Hb D resulted in the slightly higher Hb level and lower Hb D level as compared to Hb D/ betathalassemia cases [Hb D 24-37% vs 57-88%]. Co inheritance of Hb D and sickle cell results was moderate to severe hemolytic anemia

alpha-Thalassaemia in Tunisia: some epidemiological and molecular data.

Unlike the other haemoglobinopathies, few researches have been published concerning alpha-thalassaemia in Tunisia. The aim of the present work is to acquire further data concerning alpha-thalassaemia prevalence and molecular defects spectrum in Tunisia, by collecting and studying several kinds of samples carrying alpha-thalassaemia. The first survey conducted on 529 cord blood samples using cellulose acetate electrophoresis, have displayed the prevalence of 7.38% Hb Bart's carriers at birth. Molecular analyses were conducted by PCR and DNA sequencing on 20 families' cases from the above survey carrying the Hb Bart's at birth and on 10 Hb H diseased patients. The results showed six alpha-globin gene molecular defects and were responsible for alpha-thalassaemia: -alpha(3.7), - -(MedI), alpha(TSaudi), alpha(2)(cd23GAG->Stop), Hb Greone Hart: alpha(1)(119CCT->TCT) corresponding to 11 genotypes out of which two are responsible for Hb H disease (- -(Med)/-alpha(3.7)) and (alpha(TSaudi)alpha/alpha(TSaudi)alpha) and a newly described polymorphism: alpha+6C->G. The geographical repartition of alpha-thal carriers showed that the -alpha3.7 deletion is distributed all over the country, respectively the alpha(HphI) and alpha(TSaudi) seem to be more frequent in the central region of the northeast region. The haematological and clinical data showed a moderate phenotype with a late age of diagnosis for Hb H disease. This work had permitted, in addition to an overview on alpha-thalassaemia in the country, the optimization of protocols for alpha-thalassaemia detection in our lab, allowing further investigations concerning phenotype-genotype correlation in sickle cell disease or beta-thalassaemia.

Alpha+ -thalassaemia and malaria in Melanesia: epidemiological perspectives

In 1948 Haldane first proposed that the high frequencies of thalassaemias in malaria-endemic regions were due to natural selection by malaria. Some of the highest frequencies of alpha+ -thalassaemia are found in the Pacific region of Melanesia. Consequently, Melanesia has provided a unique opportunity for an extensive study of the association between alpha+ -thalassaemia and malaria. Here we review the emergence of alpha+ -thalassaemia in this region and the research that has been carried out, both from the historical perspective and the most recent developments, which may give insight into the selection of alpha+ -thalassaemia by malaria.

Prevalência de talassemias e hemoglobinas variantes no estado de Goiás, Brasil / Prevalence of thalassemias and variant hemoglobins in the state of Goiás, Brazil

As anemias hereditárias, em especial as talassemias e hemoglobinas (Hb) variantes, são as mais comuns das alterações genéticas humanas; sua frequência na população brasileira é muito variável, dependendo dos grupos raciais formadores de cada região. O povoamento de Goiás, que teve início logo após o seu descobrimento, em 1726, motivado pela procura de ouro, foi composto principalmente por portugueses e escravos africanos, contexto que favoreceu a mestiçagem entre eles. Considerando que esses povos apresentam genes para as hemoglobinas anormais com frequências variadas, é esperado que se encontrem essas alterações genéticas na nossa população. O objetivo deste trabalho foi avaliar a a prevalência de talassemias e hemoglobinas variantes na população de Goiás. Para isso a casuística foi composta por 404 alunos participantes dos diversos cursos da Universidade Católica de Goiás (UCG), oriundos de 55 cidades do estado de Goiás. A prevalência de anemia hereditária por talassemias e hemoglobinas variantes em Goiás foi de 10,1 por cento, cuja ordem decrescente foi a seguinte: talassemia alfa heterozigótica (5,2 por cento), heterozigose para hemoglobina S (Hb AS) (2,2 por cento), heterozigose para hemoglobina C (Hb AC) (1 por cento), talassemia beta menor (0,7 por cento), associa��o entre talassemia alfa e heterozigose para Hb S (0,5 por cento), associação entre talassemia alfa e heterozigose para Hb C (0,3 por cento) e heterozigose para hemoglobina D (Hb AD) (0,3 por cento). Nenhum caso de homozigose foi encontrado no presente estudo. Este trabalho demonstrou a dispersão dos genes para Hb S, Hb C e Hb D, bem como de talassemias alfa e beta em uma população do estado de Goiás. Por essa razão, concluímos que é importante realizar programas com maior abrangência da população para estudo da epidemiologia das talassemias e hemoglobinas variantes no estado de Goiás.

The hereditary anemias, especially the thalassemies and hemoglobinopathies are the most common human genetic abnormalities. Their frequency in the Brazilian population is very variable depending on the racial groups typical of each region. The settlement of Goiás, that had its beginning after discovery in 1726 owing to the search for gold, was composed basically by Portuguese and African slaves, a context that favored the racial mixing among them. Considering that these groups present genes for abnormal hemoglobins with varied frequencies it is expected the finding of these genetic abnormalities within our population. The objective of this study was to evaluate the prevalence of thalassemies and variant hemoglobins in the population of Goiás. For this purpose the sample was composed by 404 participating students from several graduate courses of the Catholic University of Goiás originally from 55 cities of the state of Goiás. Laboratory tests were used taking into account the historical and demographic factors of the population. The prevalence of hereditary anemias by thalassemias and variant hemoglobins in Goiás was 10.1 percent, in which the decreasing order of these abnormalities was: alfa heterozygous thalassemy (5.2 percent); heterozygous hemoglobin S (Hb AS) (2.2 percent); heterozygous hemoglobin C (Hb AC) (1 percent); beta short thalassemy (0.7 percent); association between alpha thalassemy and heterozygous for hemoglobin S (0.5 percent); association between alpha thalassemy and heterozygous for hemoglobin C (0.3 percent); and heterozygous for hemoglobin D (0.3 percent). No homozygosity was found in the study group. This study demonstrates the need for large scale screening in human populations for epidemiological studies of the thalassemies and variant hemoglobins in the state of Goiás.

Molecular characterization of alpha-thalassemia in the Mexican population / Caracterización molecular de talasemia alfa en una población mexicana

Background. α-Thalassemia (α-Thal) has been poorly characterized at the molecular level in Mexico. Methods. 106 consecutive individuals identified in Laboratorios Clínicos de Puebla, with either hypochromia (MCH < 24 pg) and/or microcytosis (MCV < 75 fl in women or < 80 fl in man), without iron deficiency, with or without anemia were investigated in this study, along a 16 month-period, α and β-Thal were looked for, the former were characterized at the molecular level. Results. Out of the 106 consecutive cases with hypochromia and/or microcytosis and normal levels of protoporphyrin zinc complex, 48 cases (45.3%) had thalassemia (37 cases of β-Thal and 11 cases of α-Thal), whereas in 58 cases (54.7%) a definite diagnosis could not be established. Of the α-Thal cases, 8 were heterozygous and two were homozygous for the -α3.7 deletion, whereas one case was heterozygous for the α2Hph allele. Conclusions. Only few of the α-Thal alleles tested were found, thus the α-thalassemic mutations, present in the studied population, seem to be rather heterogeneous.

Antecedentes. En México, la α-talasemia (α-Thal) ha sido pobremente caracterizada a nivel molecular. Mátodos. Se estudiaron 106 individuos consecutivos identificados en los Laboratorios Clínicos de Puebla, con hipocromia (CMH < 24 pg) y lo microcitosis (VCM < 75 fl en mujeres o 80 fl en hombres), sin deficiencia de hierro, con o sin anemia, durante un periodo de 16 meses. Se investigaron α y β-Thal; las primeras fueron caracterizadas a nivel molecular. Resultados. De los 106 casos consecutivos estudiados con hipocromia y/o microcitosis, y niveles normales del complejo de protoporfirina-cinc, 48 casos (45.3%) tenían talasemias (37 de ellos β-Thal y 11 α-Thal), mientras que en 58 casos (54.7%) no pudo establecerse un diagnóstico definitivo. De las talasemias α, ocho casos eran heterocigotos y dos homocigotos para la deleción -α3.7, mientras que sólo un caso resultó heterocigoto para el alelo α2Hph. Conclusiones. De los alelos α-Thal estudiados sólo se encontraron algunos, de lo que se infiere que en la población estudiada esas mutaciones parecen ser bastante heterogáneas.

High prevalence of alpha-thalassemia among individuals with microcytosis and hypochromia without anemia

In order to determine the contribution of alpha-thalassemia to microcytosis and hypochromia, 339 adult outpatients seen at Unicamp University Hospital (with the exception of the Clinical Hematology outpatient clinics), who showed normal hemoglobin (Hb) levels and reduced mean corpuscular volume and mean corpuscular hemoglobin, were analyzed. Ninety-eight were Blacks (28.9 percent) and 241 were Caucasians (71.1 percent). In all cases, Hb A2 and F levels were either normal or low. The most common deletional and nondeletional forms of alpha-thalassemia [-alpha3.7, -alpha4.2, --MED, -(alpha)20.5, alphaHphIalpha, alphaNcoIalpha, aaNcoI and alphaTSAUDI] were investigated by PCR and restriction enzyme analyses. A total of 169 individuals (49.9 percent) presented alpha-thalassemia: 145 (42.8 percent) were heterozygous for the -alpha3.7 deletion (-alpha3.7/aa) and 18 (5.3 percent) homozygous (-alpha3.7/-alpha3.7), 5 (1.5 percent) were heterozygous for the nondeletional form alphaHphIalpha (alphaHphIalpha/aa), and 1 (0.3 percent) was a --MED carrier (--MED/aa). Among the Blacks, 56 (57.1 percent) showed the -alpha3.7/aa genotype, whereas 12 (12.2 percent) were -alpha3.7/-alpha3.7 and 1 (1.0 percent) was an alphaHphIalpha carrier; among the Caucasians, 89 (36.9 percent) were -alpha3.7/aa, 6 (2.5 percent) had the -alpha3.7/-alpha3.7 genotype, 4 (1.7 percent) presented the nondeletional form (alphaHphIalpha/aa), and 1 (0.4 percent) was a --MED carrier. These results demonstrate that alpha-thalassemia, mainly through the -alpha3.7 deletion, is an important cause of microcytosis and hypochromia in individuals without anemia. These data are of clinical relevance since these hematological alterations are often interpreted as indicators of iron deficiency

Triagem neonatal: investigação de hemoglobinoparias em recém-nascidos da cidade do Salvador - Bahia / Neonatal screening: hemoglobinopathies investigation in newborns from Salvador - Bahia

As hemoglobinopatias apresentam freqüência mundial elevada. No Brasil, tem sido registradas freqüências elevadas para a HbS, estimando-se 0,1 a 0,3% de recém-nascidos (RN) com anemia falciforme (SS). A talassemia a apresenta freqüência de 20 - 23% entre algumas populações estudadas. Um total de 600 amostras de sangue de cordão umbilical foi investigada. Os RN foram provenientes da Maternidade Pública Tsylla Balbino (SESAB) e as amostras coletadas no período de fevereiro a junho de 2000. A análise de hemoglobinas foi realizada por eletroforese em fitas de acetato de celulose pH 8,9 e em ágar - citrato pH 6,0; os dados hematológicos foram obtidos através de contador de células eletrônico (Coulter Count T - 890). O DNA foi isolado dos leucócitos e utilizado para a investigação das talassemias α2 3.7Kb e α2 4,ZKb por PCR (Reação em Cadeia da Polimerase). Os dados referentes aos RN foram obtidos através de entrevista às mães, consulta aos prontuários médicos e observação do RN. A análise estatística foi realizada através do software EPI-INFO versão 6.04. Foram encontrados 538 (90,9%) RN com perfil de hemoglobinas normal (AF); 33 (5,6%) heterozigotos para a HbS (ASF), 19 (3,2%) heterozigotos para a HbC (ACF) e 02 (0,3%) homozigotos para a HbC (CF). O peso, gênero e idade gestacional não demonstraram associação com a presença de hemoglobinas anormais. Vinte e seis RN com perfil ASF foram distribuídos de acordo com a classificação racial: 11 (42,30%) foram mulatos, 08 (30,77%) pretos e 07 (26,90%) brancos. A análise hematológica entre os RN com padrão de AF e ASF não demonstrou diferenças estatisticamente significativas. A análise hematológica entre os RN AF e ACF apresentou diferenças significativas para os valores de Ht (p=0,008), Hm (p=0,017) e CHCM (p=0,0045). Os padrões SF e SCF não foram encontrados na análise da presente amostra. A talassemia α2 3,7 Kb foi detectada em 134 (22,71%) dos RN, entre os quais 120 (20,34%) foram heterozigotos e...

Alpha-thalassemia: deletion analysis in Iran

Alpha-thalassemia is one of the most prevalent hemoglobin disorders in the world. The molecular basis of alpha -thalassemia is deletions of variable lengths involving one or both alpha -genes at the alpha -globin gene cluster. Functional point mutations leading to inactivation of the alpha -genes are less frequent. So far, no comprehensive population screening for alpha -thalassemia has been performed in Iran and no molecular diagnostic services are available for this disease. As a result, a considerable number of patients with microcytic, hypochromic anemia and normal Hb A2 levels might be misdiagnosed as silent beta -thalassemia. The aim of the present study was to determine the spectrum of common alpha -thalassemia mutations in Iran. A total of 57 Iranian subjects were randomly chosen from a pool of patients with microcytic hypochromic anemia and negative beta -thalassemia genotyping. They were tested for the 2 most frequent alpha -thalassemia deletions [- alpha 3.7, - alpha 4.2]. Analysis was performed using deletion-specific PCR amplification followed by agarose gel electrophoresis of the resulting PCR fragments. No - alpha 4.2 deletion was detected, however, 18 [31.6%] out of 57 analyzed cases demonstrated the - alpha 3.7 deletion, either in the homozygous or heterozygous state. This study suggests that the - alpha 3.7 deletion is a common cause of microcytic hypochromic anemia in Iran. The results are in accordance with previous studies, which report a remarkably high frequency of - alpha 3.7 in the Middle East. Routine screening for this mutation will improve the molecular diagnosis of anemia in Iran

Appraisal of sickle-cell and thalassaemia genes in Saudi Arabia

A comprehensive national survey of the distribution of the sickle-cell [Hb S] gene and thalassaemia genes was initiated in 1982, with more than 30,055 blood samples collected. The Hb S, alpha- and beta-thalassaemia gene frequency range was 0.005-0.145, 0.01-0.40 and 0.01-0.15 respectively in various areas of Saudi Arabia. We present here an appraisal of sickle-cell and thalassaemia gene occurrence in the Saudi population, based on our studies conducted over 10 years in different regions of Saudi Arabia

Pattern for alpha-thalassaemia in Yemeni sickle-cell-disease patients

A group of Yemeni patients with sickle-cell disease [SCD] and normal Hb AA individuals living in Riyadh were studied to determine the incidence of the alpha-gene molecular defect. Blood samples were obtained from 26 SCD patients and 19 controls [the Hb AA group]. In the SCD patients the frequency of single alpha-gene deletion [-alpha/alpha alpha] was 0.346, compared to 0.263 in the Hb AA group. The frequency of two gene deletion [-alpha/-alpha] was 0.231 [0.0 for the Hb AA group]. In one Hb AA case, a triple alpha-gene arrangement [alpha alpha alpha/alpha alpha] was found [frequency 0.053]. The results suggest that alpha-thalassaemia occurs frequently in Yemeni SCD patients. Further studies to determine the overall frequency of alpha-thalassaemia in the Republic of Yemen would be of value for patient management

Prevalence of thalassaemia in schoolchildren in north-eastern Badia, Jordan

The prevalence of the different types of thalassaemia and that of iron deficiency anaemia was investigated in 1020 schoolchildren [age range: 6-15 years] from the north-eastern Badia region of Jordan. beta-thalassaemia minor was the most prevalent [3.04%], followed by alpha 2-thalassaemia [2.06%]. Only three cases of alpha 1-thalassaemia and one case of beta-thalassaemia major were found. Iron deficiency anaemia was diagnosed in 54 children [5.3%] [33 males, 21 females]. The mean values of the blood characteristics of the normal, haemoglobinopathic and iron-deficient children were examined and compared

Neonatal screening for sickle cell disease, glucose-6-phosphate dehydrogenase deficiency and alpha-thalassemia in qatif and al hasa

Screening programs to determine the frequency of sickle cell, glucose-6-phosphate dehydrogenase deficiency and alpha-thalassemia gene are available in Saudi Arabia, although not used frequently. Greater use of these programs will decrease the morbidity and mortality of Saudi children affected by these disorders. Neonatal hemoglobin electrophoresis and glucose-6-dehydrogcnase Fluorescent spot tests were performed on newborn babies delivered between December 1992 and December 1993 at the Qatif Central Hospital and at the King Fahad Hospital in Al Hasa. Cord blood samples were collected from babies born in these two hospitals. Babies born in other hospitals had blood collected in their first visit to Qatif primary care centers at the time of vaccination. All specimens were sent to Dammam Central Laboratory. The diagnosis of sickle cell and alpha-halassemia was based on cellulose acetate electrophoresis and confirmed by agar gel electrophoresis, and glucose-6-phosphate dehydrogenase was confirmed by fluorescent spot test. Results: A total of 12,220 infants, including 11,313 Saudis [92.6%], were screened over a 12-month period. The common phcnotypes detected in these infants included AF, AF Bart's, SFA, SFA Bart's, FS and FS Bart's. In the Saudi infants, homozygous sickle cell disease was detected in 2.35% and 1.08% in Qatif and Al Hasa, respectively. The frequencies of sickle cell gene were 0.1545% and 0.1109% in Qatif and Al Hasa. alpha-thalassemia gene based on an elevated level of Hb Bart's were 28% and 16.3% in Qatif and Al Hasa. The screening for G6PD deficiency revealed a high prevalence of 30.6% and 14.7% in Qatif and Al Hasa. In the non-Saudi infants, the frequencies were low. The outcome of this study indicates that the Saudi populations in Qatif and Al Hasa are at risk for hemoglobinopathies and G6PD. Neonatal screening programs are essential and cost effective and should be maintained as a routine practice

Prevalence and preventive measures of N.W.F.P., Pakistan

65 cases of thalassaemia major were selected out of 300 cases of anaemia [21.66%] admitted to Paediatric Unit A in Women and Children Hospital, Abbottabad since June 1995, based on their family history, clinical data, laboratory investigations and X-ray analyses. Most of them were between 1-5 years of age. No difference was noted between the two sexes. Parental consanguinity was present in 49.23% of cases and non-consanguinity in 24.61%, whereas data was not available in 26.15%, of cases. All the patients had moderate to severe anaemia and failure to thrive as their presenting symptoms. Other predominant associated features were splenomegaly [90%], typical facies [60%], skull changes on X-rays [60%], hepatomegaly [45%], jaundice [10%] and repeated infections such as gastroenteritis, pneumonia, etc. Some of them, particularly older children having received multiple blood transfusions, presented with complications such as viral hepatitis, congestive cardiac failure [4.61%] and diabetic ketoacidosis [1.53%]. A variety of problems were encountered in diagnosis and management of these cases and are listed with suggested improvements in patient care

Pyruvate kinase deficiency in an alpha-thalassemia family: first case report in Thailand.

In Thailand, the most common cause of chronic hemolytic anemia is thalassemia hemoglobinopathy. We report here a 10-year-old girl with pyruvate kinase (PK) deficiency who was initially diagnosed to have Hb H disease, like her sister. The patient had a history of neonatal jaundice which required blood exchange transfusion twice and phototherapy. She became anemic and regular blood transfusion was required since the age of 2 1/2 months. She was very anemic compared to her sister and was transfusion dependent. Besides, she never had red cell inclusion bodies, thus re-evaluation was performed. The diagnosis of red cell pyruvate kinase deficiency and the exclusion of Hb H disease was achieved after cessation of blood transfusion for 3 months. The family study also confirmed the diagnosis. The patient is now on high transfusion and iron chelation. She is doing well with mild splenomegaly.

Prevalence of hemoglobin E, alpha-thalassemia and glucose-6-phosphate dehydrogenase deficiency in 1,000 cord bloods studied in Bangkok.

Thalassemia hemoglobinopathies and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are prevalent in Thailand. We studied the prevalence of these disorders from 1,000 cord bloods collected during 14 months period, using EDTA as anticoagulant. Red blood cell G-6-PD quantitative assay was performed in all male subjects. Nine hundred and eighty five specimens were available for hemoglobin (Hb) typing by starch gel electrophoresis. Further evaluation by cellulose acetate electrophoresis and follow up were made in the cases who had Hb E and/or high level of Hb Bart's. It was found that out of 505 males, 61 cases (12.08%) had G-6-PD deficiency. Among 985 cases studied for Hb typing, 61.92% revealed normal Hb type AF while Hb E was present in 18.68% and Hb Bart's designated alpha-thalassemias were present in 25.18% respectively. Of these 985 cases, 18.78% had low Hb Bart's level ie detectable to 8.2% consistent with alpha-thal2, Hb Constant Spring (CS) or alpha-thal1 trait. Ten cases (1.02%) had high levels of Hb Bart's ranging from 16.1-35% without or with Hb CS and E, and further follow-up revealed homozygous Hb CS, Hb A-E-Bart's, Hb H and Hb H with Hb CS disease. The other 53 cases (5.38%) had low level of Hb Bart's with Hb E consistent with alpha-thalassemia trait with Hb E trait. There were 127 cases (12.89%) who had only Hb E trait and 3 cases (0.3%) who had Hb F and E without Hb A initially.