Neonatal screening for sickle cell disease in France: evaluation of the selective process.

Aims: The French national programme for neonatal screening of sickle cell disease is applied to newborns 'at risk', defined as those born to parents originating from sub-Saharan Africa, the Mediterranean area, the Arabic peninsula, the French overseas islands and the Indian subcontinent. The selection is performed by the nurse in charge of blood sampling by interviewing the mother about the family's geographical origins. The mean rate of testing in France is 25%, ranging from 2% to 50% depending on the region.

Epidemiology of haemoglobin disorders in Europe: an overview.

Objective: As a result of global population movements, haemoglobin disorders (thalassaemias and sickle cell disorders) are increasingly common in the formerly non-indigenous countries of Northern and Western Europe and in the indigenous countries of Southern Europe. This article presents an overview of the changing picture and a method for assessing service needs.

Method: Data on country of birth or ethnic origin of residents are adjusted to obtain the estimated proportions of residents and births in non-indigenous groups at risk for haemoglobin disorders in European countries.

Ethical aspects of neonatal screening for sickle cell disease in Western European countries.

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.

[Good practices for the study of hemoglobin].

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.

[Beta-thalassemia in metropolitan France].

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.

Outcome of a school screening programme for carriers of haemoglobin disease.

Objectives: To assess the impact of a screening programme for haemoglobinopathies which was organised from 1978 to 1985 in high secondary schools of the Marseille region.

Methods: Several variables that reflected the influence of this preventive programme on the uptake of prenatal diagnosis were investigated. To evaluate the partner's uptake for the testing, a letter was sent, together with an anonymous questionnaire, to all the haemoglobin carriers detected in this programme.

Molecular basis of haemoglobinopathies and G6PD deficiency in the Comorian population.

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.

A novel mechanism for thalassaemia intermedia.

Thalassaemia intermedia is a moderate form of thalassaemia resulting from various genetic defects. We report an undescribed mechanism leading to this condition: a somatic deletion of the beta-globin gene in the haemopoietic lineage of a heterozygous beta-thalassaemic patient. We did molecular studies and haemoglobin analysis of the patient and his parents.

[Glucose-6-phosphate dehydrogenase et neonatal jaundice].

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.

Two new Ggamma chain variants: Hb F-clamart [gamma17(A14)Lys-->Asn] and Hb F-Ouled Rabah [gamma19(B1)Asn-->Lys].

Two new fetal hemoglobin variants affecting the Ggamma chain are reported. Hb F-Clamart was found during investigation of a French newborn who presented with a mild microcytemia. The second variant was found during neonatal screening for hemoglobinopathies of 30,000 babies from a population-at-risk living in the Paris region.

Characterization of a new polymorphism, IVS-I-108 (T-->C), and a new beta-thalassemia mutation, -27 (A-->T), discovered in the course of a prenatal diagnosis.

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.

Serum ferritin, desferrioxamine, and evolution of HIV-1 infection in thalassemic patients.

To study the respective roles of mean serum ferritin level and the mean desferrioxamine (DFX) dose on progression of HIV-1 infection, data from 49 HIV-seropositive thalassemic patients were analyzed using a Cox proportional hazards model including known confounding variables. Nine years after seroconversion, 10% of those who had been prescribed >40 mg/kg of DFX daily had entered stage IV versus 39% of those who had been prescribed a lower dose. Patients with ferritin level >1935 g/L entered stage IV more rapidly than those with a lower level (31% versus 16%).

Hb Bruxelles, deletion of Phebeta42, shows a low oxygen affinity and low cooperativity of ligand binding.

Functional studies of partially purified hemoglobin (Hb) Bruxelles, Phebeta42 (CD1) --> 0 indicate a major shift in the allosteric equilibrium toward the deoxy (T state) conformation. While Hb A shows a roughly symmetrical oxygenation curve with maximum cooperativity near half-saturation, Hb Bruxelles shows mainly properties of the low affinity (T state) form. The oxygen equilibrium curves for purified (>80%) Hb Bruxelles show little cooperativity and a P50 (without 2,3-diphosphoglycerate) about twice that of Hb A.

[Genetic hemoglobin diseases. Prevention at centers for family planning and education of maternal-child protection in Marseille].

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.

Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta 141 (H19) Leu-->Arg.

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.

[Epidemiology of genetic hemoglobin diseases in metropolitan France].

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.

[Clinical development of beta-thalassemia-sickle cell anemia apropos of 36 cases].

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.