Universal newborn screening for haemoglobinopathies in Guadeloupe (French West Indies): a 27-year experience.

OBJECTIVES: In Guadeloupe, an island in the French West Indies, a universal newborn screening programme for sickle cell disease and other abnormal haemoglobins was initiated in 1984. In 1990, a comprehensive sickle cell centre was established to carry on the management programme. We here report the main results from the newborn screening programme from 1984 to 2010, and consider how the establishment of the sickle cell centre affected the programme. METHODS: All blood samples were screened for the haemoglobinopathies using two reference methods in a single reference diagnosis laboratory. DNA analyses were also performed for confirmatory tests and analysis of the globin gene status. RESULTS: Between 1 January 1984 and 31 December 2010, 178,428 newborns were screened at birth, and 585 children were diagnosed with major sickle cell syndromes (ie. an overall incidence of 1 in 304 births). Sickle cell anaemia (haemoglobin SS disease) was the most frequently observed (1 in 575 births), followed by haemoglobin SC disease (1 in 771 births) and haemoglobin Sß-thalassemia disease (1 in 4,243 births). Some other rare haemoglobin variants were also detected, the most common being HbD(Punjab). The establishment of a comprehensive sickle cell centre resulted in a significant improvement in the screening coverage (p < 0.001) and a significant reduction of the delay between diagnosis and the first medical visit (p < 0.001). CONCLUSION: The universal screening programme has made it possible to establish the incidence of the major sickle cell syndromes in Guadeloupe, and the management centre has improved its efficiency.

Phenotypic expression and origin of the rare beta-thalassemia splice site mutation HBB:c.315 + 1G>T.

We present the hematological characteristics of five patients from Surinam and the bordering French Guyana, who are carriers of the rare beta-thalassemia (beta-thal) mutation HBB:c.315+1G>T. Analysis of the phenotype/genotype relationship shows that this allele is a beta(0)-thal variant and illustrates the modulating effect of the alpha-globin gene status on the beta-thal phenotype. The ethnic origin of the five probands, belonging to the so-called Bush Negroes Maroons of Surinam and French Guyana, strongly suggests that this beta-thal mutation has a West African origin and spread in this ethnic group because of a founder effect and/or genetic drift.

Beta-globin gene cluster haplotypes and alpha-thalassemia in sickle cell disease patients from Trinidad.

In this study, we have determined the frequency of beta(S) haplotypes in 163 sickle cell disease patients from Trinidad. The alpha(3.7) globin gene deletion status was also studied with an observed gene frequency of 0.17. Among the 283 beta(S) chromosomes analyzed, the Benin haplotype was the most prevalent (61.8%) followed by Bantu (17.3%), Senegal (8.5%), Cameroon (3.5%), and Arab-Indian (3.2%), while 5.7% of them were atypical. This beta(S) haplotypes distribution differed from those previously described in other Caribbean islands (Jamaica, Guadeloupe, and Cuba), in agreement with the known involvement of the major colonial powers (Spain, France, and Great Britain) in the slave trade in Trinidad and documented an Indian origin of the beta(S) gene.

Does repeated and heavy exercise impair blood rheology in carriers of sickle cell trait?

OBJECTIVE: To determine if the time courses of hemorheologic parameters are different between carriers of sickle cell trait (SCT) and subjects with normal hemoglobin in response to exercise. DESIGN: Observational and comparative study. SETTING: Testing was conducted in a laboratory of exercise physiology. PARTICIPANTS: Nine carriers of sickle cell trait (SCT group) and 7 subjects with normal hemoglobin (CONT group) performed an exercise protocol of the repetition of 3 successive maximal ramp exercise tests. INTERVENTIONS: Blood was sampled at rest (TR), at the end of each of the 3 tests (T1, T2, T3), and during the immediate (T2h) and late (T24h, T48h) recovery periods. MAIN OUTCOME MEASUREMENTS: Blood and plasma viscosity (etab and etap, respectively), hematocrit (Hct), and red blood cell (RBC) rigidity (Tk and k indexes) were determined. RESULTS: In both groups, etab significantly increased in response to exercise but the SCT group had significantly higher etab at T3 and T2h. etab then returned to baseline value at T2h in the CONT group and at T24h in the SCT group. Tk and k were not changed by exercise but significantly increased above baseline value in both groups at T24h and T48h. The increase in Tk and k during late recovery was higher in the SCT group than in the CONT group, indicating that SCT carriers had significantly higher RBC rigidity than the CONT group at that time. CONCLUSIONS: The hemorheologic changes induced by exercise in the SCT carriers could trigger microcirculatory disorders during the recovery.

Effects of short supramaximal exercise on hemorheology in sickle cell trait carriers.

This study compared the hemorheological profile at rest and in response to a short supramaximal exercise test between sickle cell trait (SCT) carriers and a control group. Eight SCT carriers and eight control subjects performed a ramp exercise test on a cycle ergometer conducted to maximal oxygen uptake (VO2max). One week later, they performed a supramaximal exercise test consisting of pedaling for 1 min at 110% VO2max. Blood viscosity (eta(b)), plasma viscosity (eta(p)), hematocrit (Hct) and red blood cell (RBC) rigidity were assessed at rest, at the end of exercise and at the 15th, 30th and 60th min of recovery. Exercise increased eta(b), eta(p) and Hct above resting values in both groups and these parameters remained higher until the 15th or 30th min of recovery as compared to resting values. RBC rigidity was unchanged from baseline values in both groups during exercise and recovery. No difference was observed between the two groups for eta(p) and Hct but eta(b) and RBC rigidity were higher in the SCT carriers at every time point compared with the control group. The higher RBC rigidity and eta(b) found in SCT carriers at rest and in response to a brief supramaximal exercise might constitute a risk factor for microcirculatory complications. Indeed, a short supramaximal exercise test may not be completely inoffensive for SCT carriers.