RESUMO
The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester. Mild beta+ thalassaemia variants (-88 C>T, -29 A>G, -90 C>T, polyA T>C) accounted for 75% of Kingston newborns, 76% of newborns in southwest Jamaica, and 89% of Manchester students. Severe beta+ thalassaemia variants were uncommon. Betao thalassaemia variants occurred in 43 patients and resulted from 11 different variants of which the IVSII-849 A>G accounted for 25 (58%) subjects. Red cell indices in IVSII-781 C>G did not differ significantly from HbAA, and this is probably a harmless polymorphism rather than a form of beta+ thalassaemia; the removal of 6 cases in school screening had a minimal effect on the frequency of the beta thalassaemia trait. Red cell indices in the beta+ and betao thalassaemia traits followed established patterns, although both were associated with increased HbF levels. The benign nature of beta+ thalassaemia genes in Jamaica means that cases of sickle cell-beta+ thalassaemia are likely to be overlooked, and important clinical questions such as the role of pneumococcal prophylaxis remain to be answered.
RESUMO
Based in the parish of Manchester in central Jamaica, the Manchester Project offered free detection of haemoglobin genotype to senior classes in 15 secondary schools between 2008 and 2013. Restricting the database to 15,103 students aged 15.0-19.9 years provided an opportunity to examine the red cell characteristics of the different haemoglobin genotypes, including normal (HbAA) in 85.0%, the sickle cell trait (HbAS) in 9.7%, HbC trait (HbAC) in 3.5% and hereditary persistence of foetal haemoglobin (HbA-HPFH) in 0.4%. Compared to the normal HbAA phenotype, HbAS had significantly increased mean cell haemoglobin concentration (MCHC), red cell count (RBC), and red cell distribution width (RDW) and decreased mean cell volume (MCV) and mean cell haemoglobin (MCH), these differences being even more marked in HbAC. Compared to HbAA, the HbA-HPFH had significantly increased RDW, but there were no consistent differences in other red cell indices, and there were no significant differences in haematological indices between the two common deletion HPFH variants, HPFH-1 and HPFH-2. Although these changes are unlikely to be clinically significant, they contribute to an understanding of the haematological spectrum of the common haemoglobin genotypes in peoples of African origin.
RESUMO
OBJECTIVES: To review the history of newborn screening for sickle cell disease with especial reference to Jamaica. METHODS: A summary was done of the history, the development of associated laboratory technology and the implementation of newborn screening for sickle cell disease in Jamaica. RESULTS: Screening was initiated at Victoria Jubilee Hospital, Kingston from 1973-1981, reactivated in 1995 and extended to the University Hospital of the West Indies in 1997 and to Spanish Town Hospital in 1998. From August 2008, there was a progressive recruitment of 12 hospitals in the south and west of Jamaica which has raised the frequency of islandwide newborn coverage from 25% in 1973 to 81%. The results of this extended programme in southwest Jamaica are presented. Dried blood spots collected from the umbilical cord proved stable, cheap and efficient; mean sample collection rates were 98%, maternal contamination occurred in < 1% and caused diagnostic confusion in < 0.1%. By March 31, 2015, a total of 54 566 births have been screened, detecting 161 with homozygous sickle cell (SS) disease, 125 with sickle cell-haemoglobin C (SC) disease and 36 with sickle cell-beta thalassaemia. Of the 327 babies with clinically significant sickle cell syndromes, all except five who died within seven days of birth were confirmed by four to six weeks and recruited to local sickle cell clinics. CONCLUSION: Early detection of sickle cell disease and recruitment to clinics is known to reduce its morbidity and mortality. The methods currently detailed provide an effective and economic model of newborn screening which may be of value elsewhere.
Assuntos
Globinas/genética , Hemoglobina Falciforme/análise , Hemoglobinas Anormais/análise , Traço Falciforme/genética , Talassemia beta/genética , Adolescente , Adulto , População Negra/genética , Eletroforese das Proteínas Sanguíneas , Criança , Cromatografia Líquida de Alta Pressão , Códon/genética , Feminino , Hemoglobina Falciforme/genética , Hemoglobinas Anormais/genética , Heterozigoto , Humanos , Focalização Isoelétrica , Jamaica/epidemiologia , Masculino , Traço Falciforme/complicações , Talassemia beta/complicaçõesRESUMO
The activated protein C resistance (APC-R) ratios in 50 patients with steady state homozygous sickle cell (SS) disease and 59 healthy AA controls was measured. There was a significant reduction in median APC-R ratio in sickle cell disease compared to controls. This reduction in APC-R ratio was not explained by (1) the presence of the factor V Leiden, found in only one of 165 patients with SS disease including those tested for APC-R, or (2) the presence of lupus anticoagulants. However, the raised levels of factor VIIIC in SS patients in this study may be contributing to increased resistance to APC, which in turn may contribute to the vaso-occlusive complications of SS disease.
Assuntos
Anemia Falciforme/sangue , Transtornos das Proteínas Sanguíneas/sangue , Proteína C , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/genética , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/complicações , Transtornos das Proteínas Sanguíneas/complicações , Feminino , Homozigoto , Humanos , Masculino , Tempo de ProtrombinaRESUMO
AIM: This study was set up to determine whether or not retinal changes occur in sickle cell disease in Saudi Arabian subjects with either the Benin, which exists in the south western part of the kingdom, or Asian haplotypes in the east, and to compare the findings with those in sickle cell disease in Jamaica. METHODS: Retinal examination and fluorescein angiography were performed in 61 patients with SS disease (40 eastern, 20 south western, 1 central region) and 10 with sickle cell beta(0) thalassaemia. RESULTS: Peripheral retinal vascular changes were common, and a qualitatively abnormal vascular border believed to imply risk of proliferative sickle retinography (PSR) was significantly more common in south western SS patients and PSR was shown in one of these. There were no differences in visual acuity, the presence of peripheral retinal patches, or the circumferential or posterior extent of peripheral retinal vessel closure between SS disease and sickle cell beta(0) thalassaemia or between SS disease in the two regions. Compared with the Jamaican Cohort Study, > 180 degrees of the peripheral retinal vasculature was seen significantly less frequent, suggesting factors inhibiting vascular remodeling in Saudi patients in early life. CONCLUSION: Sickle cell disease in Saudi Arabia affects the retina and represents a potential threat to vision. Changes occur whatever the haplotype, and is similar to that observed in Jamaica.
Assuntos
Doenças Retinianas/patologia , Traço Falciforme/patologia , Adolescente , Adulto , Feminino , Angiofluoresceinografia , Haplótipos , Humanos , Jamaica , Masculino , Arábia Saudita , Traço Falciforme/genética , Talassemia beta/patologiaRESUMO
Avascular necrosis of the femoral head (ANFH) in Saudi patients with homozygous sickle cell (SS) disease attending King Faisal Specialist Hospital and Research Centre (KFSH&RC) occurred in 29/118 (24.6%) patients or 32% of patients aged 10 years and above. This high prevalence was heavily influenced by symptomatic selection. Contrary to observations in patients of African origin, ANFH in Saudi subjects was not associated with high hemoglobin, low fetal hemoglobin levels or with alpha thalassemia. Bone densitometry failed to detect differences in bone mineral density or content between patients with and without ANFH. Levels of 25-OH vitamin D did not differ between patients with and without ANFH. Several patients showed very rapid and complete destruction of the femoral head suggestive of osteomyelitis of the femoral head or a pyogenic arthritis. ANFH appears common in Saudi patients with SS disease although an accurate prevalence is unknown. The lack of relationship with risk factors for ANFH identified in African SS disease highlights the need for further study in the Saudi SS population.
Assuntos
Anemia Falciforme/etnologia , Etnicidade , África Ocidental/etnologia , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Anemia Falciforme/genética , Anemia Falciforme/patologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Globinas/genética , Hemoglobina Falciforme/genética , Humanos , Lactente , Jamaica , Masculino , Sicília , Talassemia/complicações , Talassemia/etnologia , Talassemia/genéticaRESUMO
To further explore the cause for variation in hemoglobin F (Hb F) levels in sickle cell disease, the beta globin restriction-fragment length polymorphism haplotypes were determined in a total of 303 (126 SS, 141 AS, 17 S beta(0), 7 A beta, (0) and 12 AA) Indians from the state of Orissa. The beta(s) globin gene was found to be linked almost exclusively to a beta(S) haplotype ( -++-), which is also common in Saudi Arabian patients from the Eastern Province (referred to as the Asian beta(s) haplotype). By contrast, the majority of beta A and beta(0) thalassemia globin genes are linked to haplotypes common in all European and Asian populations (+-----[+/-]; --++-++). Family studies showed that there is a genetic factor elevating Hb F levels dominantly in homozygotes (SS). This factor appears to be related to the Asian beta(s) globin haplotype, and a mechanism for its action is discussed. There is also a high prevalence of an independent Swiss type hereditary persistence of fetal hemoglobin (HPFH) determinant active in both the sickle cell trait and in sickle cell disease.
Assuntos
Anemia Falciforme/metabolismo , Hemoglobina Fetal/análise , Globinas/genética , Adolescente , Adulto , Anemia Falciforme/genética , Criança , Pré-Escolar , Haplótipos , Heterozigoto , Homozigoto , Humanos , Índia , Jamaica , Talassemia/metabolismoRESUMO
A study of 131 patients with homozygous sickle cell (SS) disease in Orissa State, India, indicated that, compared with Jamaican patients, Indian patients have higher frequencies of alpha thalassaemia, higher fetal haemoglobin, total haemoglobin, and red cell counts, and lower mean cell volume, mean cell haemoglobin concentration, and reticulocyte counts. Indian patients have a greater frequency and later peak incidence of splenomegaly, and hypersplenism is common. Painful crises and dactylitis are not uncommon in Indian patients but chronic leg ulceration is rare. Homozygous sickle cell disease in Orissa is similar to that in the Eastern Province of Saudi Arabia and is very different from that in populations of West African origin.