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Unlabelled: Sickle cell disease raises some important ethical questions regarding neonatal screening in Western European countries such as France, England or Belgium, which have already introduced either universal or selective screening. Such screening is aimed at benefiting children affected with major sickle cell syndrome. It also detects heterozygous babies and, in doing so, heterozygous parents. The latter information, which is ignored most of the time, risks making parents feel guilty and can raise fears of stigmatization. Whether it would change their future reproductive decisions requires further studies, for cultural and religious reasons may have a strong negative influence on the request for prenatal diagnosis. Disclosure of the child's illness may oblige the family to remain in the country they have emigrated to because it offers the best chance of treatment. As a result, links between the family and its original community are modified. Parents must more or less sever links with their family in Africa and try to trust and adapt to the public health services in Europe., Conclusion: Neonatal screening of sickle cell disease is highly ethical in facilitating the prevention of the early death of affected children. It also detects heterozygous parents and offers at-risk couples the possibility to perform a prenatal diagnosis during the next pregnancy. Adequate counselling must consider the risk of stigmatization that carrier status represents, especially for women in many cultural beliefs, and the numerous cultural and religious reasons which limit parental uptake for prenatal diagnosis. Disclosure of their child's illness may oblige immigrant families to stay in Europe, where free and adapted healthcare is available.

Hemoglobinopathies have become a significant national health problem in France. The biologists have a pivotal role in the genetic diagnoses. Although sickle cell disease (SCD) is the most frequent abnormality found: not less than 200 new cases are observed each year at birth, many other globin gene variations are found in the various ethnic groups. Since 1995 a neonatal sickle cell screening program has been established for at risk newborns. This programme is supported by the "Association française de dépistage et prévention des handicaps de l'enfant" (AFDPHE). The characterization of hemoglobin genetic variations requires a comprehensive set of laboratory techniques for which we specify here main clinical and technical recommendations.

Objectives: Update the data collected in 1990 in order to assess the distribution and management of thalassemic patients presently living in Metropolitan France., Methods: A survey conducted in France in the clinical and biological departments of haematology permitted collection of epidemiological, clinical and biological data in a population of thalassemic patients followed-up in metropolitan France., Results: Analysis of the replies revealed a total of 362 thalassemia with 249 beta-thalassemia major, 81 beta-thalassemia intermedia and 32 E-beta thalassemia. These patients predominated in the East of France and in the large cities. The total number of patients has remained stable over the last decade and new cases are decreasing. Among the 249 patients presenting with a ss-thalassemia major, 42 had received a bone marrow graft, whereas 207 were systematically transfused and 189 regularly underwent iron chelating., Comments: Management is standardised and efficient but could be improved on with regard to iron chelating therapy.

Objective: Since 1986, quantification of G6PD activity has been a routine test for all babies born at the public maternity hospitals of Marseilles. The objective of our study was to determine the prevalence of G6PD deficiency in the population tested and to evaluate the relative risk of neonatal jaundice in newborns with G6PD deficiency., Methods: Neonatal screening is performed on cord blood by spectrophotometric measurements of G6PD activity. A group of 7779 newborns was studied retrospectively. The occurrence of neonatal jaundice was evaluated in 85 children with G6PD deficiency and compared to 85 children with normal G6PD activity., Results: The incidence of G6PD deficiency in male newborns was found to be 2.1%. The relative risk for neonatal jaundice in the G6PD deficient population compared to the non-deficient population is estimated to be 2.6., Conclusion: Neonatal jaundice with pathological hyperbilirubinemia develops more frequently in cases of G6PD deficiency. The early characterization of G6PD activity provides an etiological diagnosis for neonatal jaundice, as well as the opportunity to give the newborn's family information concerning hemolytic crisis prevention.

Introduction: The Comoro archipelago is characterised by a high prevalence of red cell genetic disorders such as G6PD deficiency and haemoglobinopathies, being a region endemic for malaria. Over the last 15 years, the city of Marseilles in France has become the main destination for Comorian immigrants. This Comorian community includes patients with sickle cell disease, sickle cell/beta-thalassaemia trait, thalassaemias and G6PD deficiency., Materials and Methods: Allele frequencies for haemoglobin S, beta-thalassaemia and G6PD deficiency were determined from neonatal and prenatal screenings of the Comorian community. Haemoglobin fractions were detected by isoelectrofocalisation, and the quantitation of HbS, HbA, HbA(2) and HbF was performed by cation exchange high performance liquid chromatography. The molecular study involved 31 alleles carrying the betaS mutation (Cd 6 [A-->T]), six beta-thalassaemic alleles and 17 G6PD-deficient alleles, selected from a group of carriers or affected subjects., Results: Allele frequencies were 3% for haemoglobin S, 1% for beta-thalassaemia trait and 9.5% for G6PD deficiency. Molecular analysis had revealed that the African alleles are predominant, being present in almost all the subjects studied. Mediterranean alleles were found for all the beta-thalassaemia mutations and for three G6PD chromosomes out of 17., Conclusion: These data are consistent with the mixed Arab and African origin of the population of the Comoro Islands, and are of clinical interest in prenatal and newborn screening plans.

We report two new substitutions, IVS-I-108 (T-->C) and -27 (A-->T), identified in a couple at risk for beta-thalassemia. One is of Iranian origin and presents with two mutations: a new substitution of T-->C at nucleotide IVS-I-108, which is a silent polymorphism, and a previously described beta-thalassemia mutation at nucleotide -28 (A-->C). The other is from the island of Corsica, the only place in France where beta-thalassemia is endemic. He presents a new substitution of A-->T at nucleotide -27 in the TATA box, which was also found in several members of his family with the beta-thalassemia trait. The fetus was found to have inherited both these novel mutations.

Objectives: Diseases due to inherited hemoglobin disorders represent serious medical, social, and economic problems in the region of Marseille. The only effective treatment for such diseases is allogenic bone marrow transplantation. About 200 patients with either thalassemia, sickle cell or sickle cell-beta thalassemic diseases are regularly seen in local hospitals. All of these patients come from parts of the world where genetic hemoglobin disorders are endemic., Methods: At this time, the only approach for reducing the number of affected children born is preventive. This depends upon education, the detection of carriers, genetic counselling and sometimes, prenatal diagnosis. We have organised a program of prevention supported by a grant from the DISS (Direction des Interventions Sociales et Sanitaires) in the context of visits made to the PMI (Prevention Maternelle et Infantile). This initiative concerns women presenting for consultations for three reasons: for a prenuptial check-up, for a pregnancy, and for prescription of contraceptives., Results: In each of these three situations a check-up is obligatory and, for natives of countries where hemoglobin disorders are common, a hemoglobin test is recommended. If this test reveals an abnormality, the partner or husband is also tested, if he is willing. Couples who are both carriers are given genetic counselling., Conclusion: This preventive initiative has yielded valuable results so we hope to follow-up on the approach and extend it to other centers. Such screening, based upon the geographic origins of patients, can be implemented in the course of a consultation by any doctor.

We report a case of severe priapism occurring in a patient with an unstable hemoglobin, Hb Olmsted (beta 141 Leu-->Arg) This is a rare hemoglobin variant, which until now has been reported only once. The clinical course of the 12-year-old boy was characterized by severe hemolytic anemia leading to splenectomy and cholecystectomy at the of 3.5 years. The priapism occurred 8 years after splenectomy, during a hemolytic febrile episode and required aspiration of the corpora cavernosa. This report raises the question of the benefit of splenectomy in patients suffering from a chronic hemolytic anemia such as that due to an unstable hemoglobin. This treatment lowers the frequency and the severity of acute hemolytic attacks, but several cases of vascular complications have been reported after splenectomy.

The number of subjects with heterozygous beta-thalassaemia and sickle-cell anaemia in metropolitan France can be evaluated by the distribution of populations originating from countries with a high prevalence of genetic haemoglobinopathies. Taking into account the movements of these populations observed since the 1982 census, the current prevalences of beta-thalassaemic and drepanocytic traits are higher than the figures of 180,000 and 130,000 respectively found at that date. On the other hand, it appears from episodic screenings performed during the last few years that the percentage of subjects with heterozygous beta-thalassaemia is 3.09% in Corsica, 0.77% in school-age population in the Marseille area, and 0.72% in the general population of Marseille, Toulon and Nice. In 1992, the number of patients with heterozygous beta-thalassaemia and with major sickle-cell syndrome is estimated at 250-350 and 1000-3000 respectively. Patients with sickle-cell anemia predominate in the Paris area, whereas those with heterozygous beta-thalassemia predominate in the provinces, notably in the Provence-Côte d'Azur and Corsica regions.

Hematological and clinical features of 36 mainly Algerian patients with S-beta thalassemia are reported. These data, compared with those reported in the literature, showed a higher prevalence of aseptic necrosis and gall stones, probably related to the large predominance of S-beta zero-thalassemia (30 cases) and a long (14 years) median follow-up period.

Hb Bruxelles is a new beta-globin variant producing severe congenital Heinz body anemia. It results from the deletion of one of the two adjacent phenylalanines, beta 41 or beta 42, presumably by frameshift mutagenesis. Its whole blood oxygen affinity is significantly lowered.

A systematic screening for thalassemias and hemoglobinopathies was performed in 35,289 children with a double test associating blood cell counts and hemoglobin electrophoresis. Four hundred thirty-seven (1.23%) hemoglobin abnormalities were found, consisting of 274 cases with thalassemia (0.77%) and 159 hemoglobinopathies (0.45%) among which there were 80 cases with sickle-cell trait (0.22%), 30 with hemoglobin C (Hb C) (0.08%), 19 with Hb D (0.05%), 12 with HbJ (0.03%), 12 with Hb E (0.03%). There was an obvious ethnic influence as, among 17,180 autochtonal French children, only 15 abnormalities were found (0.08%) while 392 were found in 16,850 non autochtonal children (2.32%) and 30 in 1,259 French children from Corsica (2.38%). The highest incidence was found in Italians (173 of 6,455-2.68%) and Maugrabins (105 of 3,014-3.48%).