Epidemiology and screening of sickle cell anemia in the Mediterranean area and in developing countries.

This article reviews the epidemiology and screening of sickle cell anemia in the Mediterranean area and in developing countries. Its aim is to create awareness of the global health burden of this condition, which is one of the most common genetic diseases worldwide. The constantly growing incidence of this condition, also caused by recent migrations, has induced the World Health Organization to pressure national health systems to strengthen prevention programs and to recognize it as a public health problem. However, scarce financial resources hinder implementation of activities.

Carrier screening for inherited haemoglobin disorders among secondary school students and young adults in Latium, Italy.

To reduce the incidence of ß-thalassaemia major and other severe haemoglobin-related disorders by the early identification of healthy carriers, the Centro Studi Microcitemie Roma has been organising since 1975 a prevention programme in Latium, an Italian central region. This programme entails two different types of carrier screening on a voluntary basis: a universal screening offered to secondary school students and a screening offered to young adults. In 36 years of scholastic screening (from 1975 until 2011), 1,466,100 students have been examined and 26,786 (1.8 %) carriers of non-α thalassaemia have been identified. In the extra-scholastic screening, 388,690 adult subjects (including the carriers' relatives) have been examined and a total of 38,457 (9.9 %) carriers of non-α thalassaemia have been detected. These results demonstrate that the precocious identification of healthy carriers allowed the identification of at-risk couples and reduced to zero the birth of affected babies in the Latium native population. This programme does not involve huge resources and is relatively inexpensive and, as such, it is essential to be offered to the total Latium scholastic and extra-scholastic population, which is epidemiologically changing due to migratory fluxes from countries in which haemoglobin disorders are common.

Providing appropriate genetic information to healthy carriers of hemoglobinopathy can be a welcome and safe initiative: the Latium example.

AIMS: To register the opinions and feelings of (presumed) unaware healthy hemoglobinopathy carriers, receiving information on their carrier status. METHODS: We collected 259 interviews from the parents of secondary school students, after their children had been provisionally diagnosed as hemoglobinopathy carriers during the routine school screening campaign imbedded in the public health care program of the Latium region (Central Italy). After screening of the children, all parents received a standard reassuring letter informing them about the presumed healthy carrier status of their children and were invited for a confirmation of the trait and for an additional explanation if needed. RESULTS: We have analyzed 219 interviews (84.5%) from indigenous subjects and 40 from allochthonous people (15.5%) being either recent immigrants or mixed couples. The average age of the parents was 45.5 years. Only 51 (19.7%) had previous knowledge of their carrier status, while the rest were unaware. When reading the letter with the provisional diagnostic result of their child, emotions that could be considered undesirable were present in about 60% of the cases. Nevertheless, the information was experienced as welcome, clear, and useful by 100% of the participants. When asked about the option of prenatal diagnosis (PD) in case of genetic risk, 85.7% and 87.5% of the autochthonous and allochthonous interviewed declared either to be in favor or to eventually consider PD, while only 14.3% and 12.5% would not consider it for various reasons. DISCUSSION: During our study, we registered undesirable feelings as well as welcome reactions: the first being experienced during the very first reading of the letter and the second after reflection on and understanding of the content during the visit to the center later on. Significantly, satisfaction and understanding of the advantage of knowledge was registered in 100% of the cases during our enquiry.

Current Genetic Epidemiology of ß-Thalassemias and Structural Hemoglobin Variants in the Lazio Region (Central Italy) Following Recent Migration Movements.

The aim of this study was to describe the changing pattern of mutational spectrum of ß-thalassemia (ß-thal) in the Lazio region (Central Italy), as consequence of recent demographic variations. From 1994 until present, 256 immigrant subjects with hemoglobin disorders (including 191 heterozygotes and 65 homozygotes or compound heterozygotes) coming from 44 different foreign countries, have been molecularly characterized. 14 ß-globin gene mutations were identified and their frequencies reflect different ethnic origins: 8 of these mutations account for 76.97% of all molecular defects, while 6 of them are much rare, representing less than 2% of the total. These data differ, both in type and percentage, from the mutational spectrum detected in the native population in 1995. Since a few defects are prevalent in each country, a proper strategy for the identification of mutations in immigrant individuals relies on the prior knowledge of their frequency in native ethnic group.

Hb L'Aquila [beta106(G8)Leu-->Val, CTG-->GTG]: a novel thalassemic hemoglobin variant.

A new beta-globin variant at codon 106 (CTG-->GTG), and which we named Hb L'Aquila [beta106(G8)Leu-->Val], was detected by DNA analysis. The proband and her father presented with the features of a mild beta(+)-thalassemia (thal), confirmed by their alpha/beta-globin chain biosynthesis ratios.

Detection of a rare beta-globin nonsense mutation [codon 59 (AAG-->TAG)] in an Italian family.

In this study we report on the hematological and molecular findings of a family from Central Italy, whose 33-year-old male proband presented with a beta0-thalassemia (thal) trait associated to a relevant Hb F level. The proband and his family (parents and a sister) were investigated by hematological analysis. The two beta-thal carriers of the beta-globin nonsense mutation [codon 59 (AAG-->TAG)] (the proband and his father) showed the hematological picture of a beta0-thal trait: the only hematological difference between the two beta-thal carriers was in the Hb F level (3.3% in the proband and 1% in his father).

Factors regulating Hb F synthesis in thalassemic diseases.

BACKGROUND: The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo) and Hb F, between Hb F and point mutations of the gamma gene promoters. MATERIALS AND METHODS: Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. RESULTS: Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta degrees or severe beta+ thal mutations are associated with evident beta thal int (88%) and almost invariably (98%) with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo) level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. CONCLUSIONS: The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients.