[Neonatal screening for sickle cell disease at the Nice University Hospital: the last 8 years]. / Dépistage néonatal de la drépanocytose au CHU de Nice : bilan des 8 dernières années.

INTRODUCTION: Screening for sickle cell disease, the most common of recessive autosomic hemoglobin disorders, allows detection of sickle cell disease SCD (homozygous sickle cell disease, compound heterozygote SC, and S ß-thalassemia) in a target population. Our objective was to evaluate its effectiveness at the Nice University Hospital. POPULATION AND METHODS: This prospective study was conducted between 1 January 2000 and 31 December 2008. The national targeted newborn screening, run together with the Guthrie test on the 3rd day of life, offered at-risk newborns (based on ethnicity and family history), allow the detection of qualitative hemoglobin abnormalities. A confirmatory test is performed when positive. Gender, ethnicity, type of hemoglobin found, zygosity, age at diagnosis, the presence at a 2nd consultation of the families identified, and acceptance of the confirmatory test were collected and analyzed. RESULTS: A total of 19,775 children were born in Nice University Hospital during this period, among whom screening detected 151 hemoglobinopathies: 139 heterozygotes and 12 major sickle cell syndrome (9 SS and 3 S ß-thalassemia). The prevalence of SCD on the targeted and the total population was, respectively, 1 out of 659 and 1 out of 1648 and the prevalence of heterozygotes was 1 out of 57 and 1 out of 142. The sex ratio was close to 1. Hemoglobin S predominated (74% of pathogens Hb). The Maghreb and sub-Saharan Africa were the 2 main areas of origin. One hundred and four of 151 families, including 12 cases of SCD, returned to consultation after they received a letter requesting attendance at a 2nd consultation. For 80 children, the confirmatory test was accepted. Feedback was possible for 72 of the 80 families. DISCUSSION: The number of children screened is increasing, thanks to better awareness among medical staff. The prevalence of SCD and heterozygotes found in Nice University Hospital is similar to what is described in the literature. With screening, early diagnosis allows early treatment at the age of 2 months before the occurrence of complications, reducing morbidity and mortality. CONCLUSION: Screening for sickle cell disease appears effective in Nice. It seems necessary to continue focusing on the importance of screening among maternity healthcare actors.

[Good practices for the study of hemoglobin]. / Bonnes pratiques de l'étude de l'hémoglobine.

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.

Hb Cemenelum [alpha 92 (FG4) Arg-->Trp]: a hemoglobin variant of the alpha 1/beta 2 interface that displays a moderate increase in oxygen affinity.

Hb Cemenelum [alpha 92 (FG4) Arg-->Trp] carries a structural modification at the same position as Hb Chesapeake, a very high oxygen affinity variant. Hb Cemenelum was found in a French diabetic patient with no abnormal hematological features. The purified abnormal hemoglobin, like Hb J Cape Town, another variant of position alpha 92(FG4), displayed only a 1.5- to 2-fold increased oxygen affinity and a reduced cooperativity. This hemoglobin demonstrates that, even for some key residues of the alpha 1/beta 2 interface, the degree at which the functional properties are altered depends upon the specific residue occupying this position.

[Application of derivative spectrophotometry for determining plasma hemoglobin and semi-quantitative evaluation of urinary porphyrins]. / Application de la spectrophotométrie dérivée au dosage de l'hémoglobine plasmatique et a l'évaluation semi-quantitative des porphyrines urinaires.

We described a method using second-derivative spectrophotometry with a spectrophotometer Uvikon (Kontron) for the assay of plasma hemoglobin and urinary porphyrins. We evaluated the procedure for sensitivity, linearity, analytical recovery. Non specific interference is not significant and reproductibility is excellent. This simple, rapid, sensitive, not expansive method can be adapted for use in a clinical laboratory.

Genetic regulation of gamma gene expression: study of the interaction of beta-thalassemia with heterocellular HPFH.

A family has been observed which a gene for heterocellular hereditary persistence of fetal hemoglobin (HPFH), probably identical to that previously described as Swiss type HPFH, has been inherited together with beta-thalassemia. The interaction of these two genes resulted in beta-thalassemia heterozygotes with unusually high levels of fetal hemoglobin (3.6-6.15), heterogeneously distributed. Globin synthesis studies showed a similar degree of chain imbalance in the heterocellular HPFH-beta thalassemia compound heterozygotes and in the heterozygous beta-thalassemia member of the family. On the basis of the pattern of genetic transmission of these two characters it can be concluded that the HPFH determinant does not behave as an allele of the gamma beta delta complex.

[Bidimensional electrophoresis in the study of cerebrospinal fluid protein (author's transl)]. / Apports de l'immuno-électrophorèse bidimensionnelle dans l'étude des protéines du liquide céphalo-rachidien

The authors report 650 bidimensional electrophoreses of the cerebrospinal fluid (CSF). All examinations were carried out after prior concentration of CSF protein. The technic used is that described by Rebeyrotte in 1970. Four types of tracing were noted: -- Two tracings were unusual by the presence of a large peak in the alpha-2 region. -- One tracing was of the hypergamma type. -- One tracing was comparable to serum by the richness of the precipitations. A change in the first migration permitted us to obtain electrophoretic separations from 100 microlitres of pure CSF. The bidimensional immunoelectrophoresis tracings are comparable to those described previously.

Miniature chromatography of haemoglobin A2 and heterozygous beta thalassemia.

172 beta thalassemias are detected by applying a new method of haemoglobin A2 determination: Miniature chromotography on DEAE cellulose. This procedure is simple, fast, accurate and there is no significant difference with macro-chromatography. It is proposed as standard method for determination of hemolgobin A2. This study was made on 400 patients suspected of beta thalassemia, the majority of which presented with a considerable microcythemia.

[Frequency of thalassemia in the South-East of France]. / Fréquence de la Thalassémie dans le sud-est de la France

The ethnic and demographic characteristics of the Nice region are predisposing factors in the locally increased frequency of Thalassemia. The use of electronic blood-cell counters has enabled us to pick out easily all those patients presenting with microcytosis. In these patients, foetal hemoglobin, electrophoresis on cellulose acetate and level of hemaglobin A2 by the technique of miniature chromatography on DEAE-cellulose have been analyzed. 270 heterozygotes thalassemics were found in 900 examinations. The statistical study shows an incidence 2% of beta-thalassemia in the Nice region.

[The utilization of EB 51 in parenteral feeding. Clinical, biological and anatomopathological control. Statistical study on 30 patients]. / L'utilisation de l'eb 51 en alimentation parentérale. Contrôle clinique, biologique et anatomopathologique. Etude statistique sur 30 malades

Two groups of patients (comas of central origin and serious digestive undernourished) were submitted to an exclusive or a supplementary parenteral feeding for a short or a long period of time totaling over 500 days. The catheter was placed (in 80 p. cent of the cases) in a deep vein and was tunnellized. EB 51 (Trivemil) used in those 30 patients gives amino-acids, lipids and glucides. The caloric intake was completed by 30 p. cent glucose solutes. If the average caloric intake was 3.000 calories per day, it was often above that figure since the feeding was combined with a nutri-pump enteral feeding for 60 p. cent of the days. The clinical tolerance was quite good. On a biological level, in addition to classic investigations, 40 analytic graphic records of lipid levels were made, as well as a quantitative analysis of serous triglycerides and lipurias, a study of sorbitol and 500 nitrogen balances combined with 150 chromatographies on the acidaminuria column. An hepatic biological control was also made (amnoniemia, transaminases) as well as a quantitative analysis of lactates, pyruvates and minerals: iron-phosphorus-magnesium. Some of the results were checked by statistical studies. No serious anomaly was detected. Lung and hepatic biopsies carried out upon 9 patients did not apparently reveal any lipidic overloading. The clinical and the biological investigation show that this complete nutriment is perfectly tolerated and assimilated.

[Transformation of sorbitol to mannitol when used in parenteral administration]. / Transformation du sorbitol en mannitol lors de son utilisation par voie parentérale

This was shown by the unexpected discovery of the urinary excretion of mannitol when urinary sorbitol levels were being measured in connection with the surveillance of patients suffering from malnutrition and head injury and receiving total parenteral nutrition: glucose, sorbitol, amino-acids, soya oil. The presence of mannitol in the urine would appear to result from a secondary catabolic through physiological pathway for the fructose produced by the metabolism of sortibol not metabolised during glycolysis.