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Background and Objective: Thalassemias are the most common single-gene disorders in the world population and the most important health problem in several countries. The best program of prevention of new births is prenatal diagnosis. Here we gather the experience from 1996 of the Spanish Group of Erythropathology related to the prenatal diagnosis of hemoglobinopathies in Spain., Subject and Method: 36 couples carriers of beta-thalassemia or Hb S were studied. Fetal material was obtained by amniocentesis and BCV. The genotype was determined by molecular biology technologies., Results: We observed 3 spontaneous abortions (8.3%), 6 interruptions of pregnancy (16.7%) and a case of maternal contamination (2.8%). Prenatal diagnosis could be completed in 97.2% of the cases (35)., Conclusions: In our experience, with regards to hemoglobinopathies, it is essential to provide a good genetic advice in order to identify the molecular alteration in the progenitors before the first pregnancy. This would allow a prenatal diagnosis during the first quarter and, in case of a positive result, to perform an early interruption of the pregnancy without risks.

The propositus is a two year old child with a severe hemolytic anemia and increased level of Hb F. The Hbs A, A2 and F were eluted and quantitated by cation exchange high-performance liquid chromatography (HPLC-CE). DNA was isolated from peripheral blood leukocytes by a salting-out extraction procedure. The beta globin gone was amplified and the presence of the beta thalassemia mutation was determined by PCR followed of Reverse Dot Blot. Her hematological parameters were as follows: Hb: 7.0 g/dL, Hct: 24.8%, VCM: 87.4 fl, CHCM: 27.8 fl. The haemoglobin study showed an 97% increase of Hb F and Hb A2 normal. The molecular study suggested the presence of beta(IVSII-829) mutation in trans to deltabeta Thalassemia. The propositus inherited her mother's deltabeta-thalassemia gene mutation and her father's beta(IVSH-829) mutation. This is the first time the diagnosis has been performed in a Venezuelan family at-risk of compound heterozygotes for beta-thalassemia and delta beta-thalassemia.

Purpose: Was to establish the molecular genetics of thalassemias in Argentina., Patients and Methods: Genomic DNA was amplified by PCR and six point mutations in the beta-globin gene were investigated by Dot Blot hybridization using oligonucleotide probes. The most frequent alpha-thalassemia deletions were studied by Southern Blotting. Patients were distributed in 4 groups: a) 109 beta-thalassemic carriers; b) 15 thalassemia major patients; c) 2 thalassemia intermedia patients and d) 14 probable alpha-thalassemic carriers., Results: The distribution of mutated alleles in the group a) was: IVS-1 nt 1: 13.76%, IVS-1 nt 6: 7.34%, IVS-1 nt 110: 23.85%, codon 39: 39.45%, IVS-2 nt 1: 3.68% e IVS-2 nt 745: 1.83%, 10.01% could not be determined with the probes used; in the group b) the allelic distribution was similar and the compound genetic genotype were predominant related to homocygous ones; in the group c): we confirmed the presence of one beta-thalassemia mutation and a alpha gene triplication (alpha alpha alpha) in the 2 patients studied. The alpha-thalassemia character was confirmed in 8 patients of the group d) (6 had -alpha 3,7/alpha alpha genotype and 2,-alpha 3,7/-alpha 3,7 genotype)., Conclusions: This study indicates that the analysis of 6 mutations in the beta-globin gene and the alpha-globin gene deletions are an effective strategy to identify thalassemias in Argentina.

Thalassemia intermedia is a clinical entity characterized by moderate, non-transfusional anemia and hepatosplenomegaly. This phenotype can result from different genetic combinations and is sometimes present in patients with only one parent showing the thalasemia minor phenotype. We report here a family with seven members with the thalassemia beta trait, four of them with thalasemia minor and the other three with thalassemia intermedia. The genetic study of patients with thalassemia intermedia revealed the presence of the mutation IVS-1 1(G-->A) in the beta-globin gene and the heterozygous triplication of the alpha-globin gene, an uncommon association in Spain. The interaction of a mutation in the beta-globin gene with triplication of the alpha-globin gene should be considered in the diagnosis and genetic counselling in those patients with thalassemia intermedia and one normal parent.

A case of non immune hidrops foetalis caused by severe hemolytic anemia secondary to a familiar thalassemia is presented. The diagnosis was made at 28 weeks of gestational age; treatment was intravascular transfusion, done in our service. The diagnosis, prenatal management and neonatal evolution are analyzed.

We have identified the case of a 9-months-old girl with heterozygotic thalassemia and triplication of alpha genes of globin (alpha alpha alpha 3.7). Molecular defect of thalassemia was a mutation without sense of 39 codon. Patient's phenotype was an intermediate thalassemia with moderate splenomegaly and marked unbalance on the globin chains. This is the first case of intermediate thalassemia, through this mechanism, described in Spain.

We present the case of a 48-year-old premenopausal woman with right lumbosciatalgia secondary to osteoporosic vertebral collapses. Two of her three offsprings, a 31-year-old man and a 16-year-old woman, had chronic dorsolumbalgia, the study of which suggested the diagnosis of minor beta-thalassemia. As opposed to thalassemic osteoarthropathy, frequently observed in the forms of "major" and "minor" beta-thalassemia, rheumatic manifestations have almost never been described in the "minor" forms. We highlight the possibility of symptomatic osteoporosis as the first manifestation and we review the locomotive disorders associated to this hemoglobinopathy.

A patient with thalassemia minor (TM) is reported who ingested 80 g of alcohol/day and presented an important overload of iron with deposits and a hepatic iron ratio compatible with primary hemochromatosis. The results obtained from the study of histocompatibility antigens, clinical manifestations and family analysis discarded the possibility of two genetic diseases, beta-thalassemia and primary hemochromatosis, being concomitantly present in the same progeny. Thalassemia minor and alcoholic hepatopathy are considered as having acted together and being responsible for the iron overload. The relation between alcohol ingested, TM and iron deposits is discussed.

Thalassemia has been considered a recessive, autosomic, hereditary disease, characterized by microcytic, hypochromic, hemolytic anemia, which occurs as the consequence of a defect in the synthesis of the globin chains, the two most frequent types are thalassemias a and b, which in their most severe forms are known as Hydrops Fetalis and Major Thalassemia. The patients who bear thalassemia are concentrated to those places on earth where malaria is endemic, including the Mediterranean region, Northern Africa, The Middle East, India, China and Southern Asia. The simple Heterozygotic states in both types of thalassemia are more benign and may go unnoticed or confused with iron deficiency.

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual hematologic values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha 0-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha (+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (--MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (--SEA) and (--SPAN) and the "no-deletion" thalassaemias.

The prevalence of beta thalassemia (B-thal) in Mexico is largely unknown, and it is thought that the disease is confined to populations with Mediterranean ancestors. Various reports suggest that in certain parts of the coast in the Gulf of Mexico the prevalence of both B-thal and hemoglobin S disease/trait is high. We studied prospectively a town with 11,000 inhabitants named Tamiahua, located along the Gulf Coast, in the State of Veracruz, and very close to the State of Tamaulipas. A group of 200 inhabitants was initially studied: the prevalence of B-thal was 15% and 6% of them had sickle cell trait. The prevalence of B-thal is the highest reported in the country. In a second part of the study, two family trees with members heterozygous for B-thal and/or Hb S trait were constructed. The ethnic characteristics of the studied population makes unlikely that the gene was derived from white Europeans but not from black Africans. Inasmuch as the indians living in that part of the country belong to the macro-maya glotochronological group, where a relatively high prevalence of B-thal has also been identified, we feel that it is possible that B-thal was present in our country before the Spaniards arrived to Mexico.

The results of a programme for the study of atypical familial microcytosis are analysed in this paper. The techniques used were "in vitro" synthesis of globin chains in tritiated leucine-labelled reticulocytes and genetic mapping with different restriction enzymes, plus the usual haematimetric values. Of the 134 syntheses performed, 73 showed alpha/beta ratio lower than 1 (alpha-thalassaemia). The lowest values, alpha/beta ratio of 0.54 +/- 0.14, corresponded to 3 patients with Hb H disease. In general terms, our findings are similar to those reported in the literature. The genetic mapping was performed in 98 patients with alpha-thalassaemia (73 cases with decreased alpha/beta ratio, 2 cases with normal ratio, and 23 relatives). Of the 98 patients, 3 had Hb H disease, 70 corresponded to heterozygous alpha zero-thalassaemia, 11 to homozygous alpha(+)-thalassaemia, and 14 to heterozygous alpha(+)-thalassaemia. The analysis of DNA revealed the heterogeneity of the molecular alterations, the prevalent haplotypes being (- -MED), in 74% of the patients, and (-3.7 alpha), in 100% of the cases. The other alpha zero-thalassaemia mutations found were the deletions (- -SEA) and (- -SPAN) and the "no-deletion" thalassaemias.

The high prevalence of beta-thalassemia minor and the occurrence of thalassemia major in Minorca prompted us to develop a prevention campaign. The selected population consisted of primary school students. The campaign was operative during the terms 1986-87 and 1987-88 and had three stages: 1.) informative; 2.) analytical study and diagnosis of carriers; 3.) report of the results and genetic counselling. We studied overall 1862 schoolchildren. The prevalence of beta-thalassemia minor was 3.38%. We discuss the methodology, the results and the effectiveness of the campaign.

Red-cell deformability was assessed with the Hanss' haemorheometer in 63 carriers of the thalassaemic trait (20 beta and 43 delta beta). Impaired deformability (rigidity index 10.5 +/- 1.4) was present in 80% of the carriers of both beta- and delta beta-traits, as compared with a control group (rigidity index 8.7 +/- 0.6). No correlation was found between such indices and several parameters capable of influencing upon red-cell deformability, namely, MCV, MCH, RDW and MDA. The possibility of any impairment of lipid compounds in red cell membrane is suggested as a cause of decreased deformability in thalassaemia carriers.

A review of hemoglobinopathies in the Caribbean basin, shows a clear association with race: In Costa Rica, evidence suggests two geographic origins for populations of African origin.

Two new cases of hemoglobin S-beta thalassemia are being reported. Twenty-six relatives are studied. The two cases were classified as Mediterranean variety. The diagnostic problem and the therapeutical possibilities are considered.

Five cases of thalassaemia intermedia are reported, they being considered from clinical and biologic standpoints. All patients had long-lasting anaemia, variable enlargement of spleen and low transfusion requirements. The ferro-erythrokinetic pattern was that of chronic haemolysis with effective erythropoiesis, and some comments are included on the different patterns found in each genetic variety. None of the patients is subjected to a defined transfusion protocol.