Newborn screening for abnormal haemoglobins in Jamaica: Practical issues in an island programme.

Objective: To report the diagnostic challenges of newborn screening for abnormal haemoglobins.

Setting: Cord blood samples from 13 hospitals in southwest Jamaica taken in 2008-2019.

Methods: Blood spots, collected from the umbilical cord, were analysed by high pressure liquid chromatography (HPLC) to reveal phenotypes for HbSS and HbCC, but genotype confirmation may require parental studies or gene sequencing.

Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassemia, and fetal hemoglobin in HbSS.

Introduction: The hematological and clinical features vary markedly between the different genotypes of sickle cell disease. Even within the single genotype of homozygous sickle cell disease (HbSS), there is marked variability that is presumed to result from interacting genetic and environmental factors.

Areas Covered: The classification of the different genotypes of sickle cell disease with approximate prevalence at birth in different communities and some of the major clinical and hematological differences.

Sickle Cell Disease: Thoughts for India From the Jamaican Cohort Study.

The sickle cell gene in India represents a separate occurrence of the HbS mutation (the Asian haplotype), which has occurred against a genetic background characterised by high levels of fetal haemoglobin and widely varying frequencies of alpha thalassaemia. These features, which tend to inhibit sickling, change the expression of the disease, which, in India, may be further modified by poor nutrition, malaria and other infections, and limited public health resources. Sickle cell disease in Jamaica is predominantly of African origin (the Benin haplotype) and faces some similar challenges.

Odisha Revisited: A Personal Account.

In 1986, a paper in the Lancet was the first to collate hematology, molecular findings, and clinical features of homozygous sickle cell (SS) disease in India. The paper came from the group organized by Professor Bimal Kar in Burla Medical College, Sambalpur University, in western Odisha. Although widely quoted, few readers will be aware of the history of this work that is now attached in an informal summary.

Homozygous sickle cell disease in Central India & Jamaica: A comparison of newborn cohorts.

Background & Objectives: Homozygous sickle cell (SS) disease in Central India runs a more severe clinical course than reports from other areas of India. The current study was undertaken to compare the disease in Central India (Nagpur) with that in Jamaica, both populations defined by newborn screening.

Methods: The Nagpur cohort included infants born to sickling-positive mothers from May 2008 to 2012, examined by high-pressure liquid chromatography and DNA analysis.

β-Thalassemia Mutations in Jamaica: Geographic Variation in Small Communities.

Over the last 43 years, surveys of over 200,000 subjects in Jamaica have identified β-thalassemia (β-thal) mutations. In most, these genes were detected at birth in patients with sickle cell-β-thal and so the prevalence and distribution would not be influenced by subsequent clinical course. There were two newborn populations, 100,000 deliveries in the corporate area between 1973-1981 and 84,940 in south and western Jamaica between 2008-2016.

Causes of death and early life determinants of survival in homozygous sickle cell disease: The Jamaican cohort study from birth.

Globally, the majority of persons born with sickle cell disease do not have access to hydroxyurea or more expensive interventions. The objectives were to estimate the survival in homozygous sickle cell disease, unbiased by symptomatic selection and to ascertain the causes of death in a pre-hydroxyurea population. The utility of early life biomarkers and genetically determined phenotypes to predict survival was assessed.

A Plea for the Newborn Diagnosis of Hb S-Hereditary Persistence of Fetal Hemoglobin.

The gene for hereditary persistence of fetal hemoglobin (HPFH) in the Caribbean is much more common than previously estimated. To avoid labeling persons with the benign syndrome Hb S (HBB: c.20A>T)/HPFH as a disease and wasting scarce resources, parental studies are recommended when newborn screening reveals a pattern consistent with an SS phenotype.

The Bone Pain Crisis of Sickle Cell Disease and Malaria: Observations from Gujarat, India.

Background: Sickle cell disease is a common problem across central India, but its clinical features may differ from that in African populations. There is a need to define the features of sickle cell disease in India, and the current study addresses some features of the bone pain crisis.

Objectives: The objective of the study was to describe the epidemiology of the bone pain crisis of sickle cell disease in Gujarat and explore the relationship with infection by .

Variability of homozygous sickle cell disease: The role of alpha and beta globin chain variation and other factors.

The single base molecular substitution characterizing sickle cell haemoglobin, βglu→val, might be expected to result in predictable haematological and clinical features. However, the disease manifests remarkable diversity believed to reflect the interaction with other genetic and environmental factors. Some of the genetic modifiers include the beta globin haplotypes, alpha thalassaemia, factors influencing the persistence of fetal haemoglobin and the effects of the environment are addressed in this review.

Evolving locally appropriate models of care for indian sickle cell disease.

The sickle cell gene in India represents a separate occurrence of the HbS mutations from those in Africa. Sickle cell disease in India occurs against different genetic and environmental backgrounds from those seen in African patients and there is evidence of clinical differences between the populations. Knowledge of the clinical features of African disease was drawn from the Jamaican Cohort Study, based on prospective follow up of all cases of sickle cell disease detected by the screening of 100,000 consecutive newborns in Kingston, Jamaica, and supplemented by observations from the Cooperative Study of Sickle Cell Disease in the US.

Pregnancy in sickle cell-haemoglobin C (SC) disease. A retrospective study of birth size and maternal weight gain.

Objective: To assess pregnancy and fetal outcomes in Jamaican subjects with sickle cell-haemoglobin C (SC) disease.

Study Design: A retrospective chart review over 21 years (1992-2012) of all pregnancies in SC disease and a comparison group matched by gender and date of delivery in mothers with a normal haemoglobin (AA) phenotype at the University Hospital of the West Indies, Jamaica. There were 118 pregnancies in 81 patients with SC disease and 110 pregnancies in 110 in the normal comparison group.

Prevention of sickle cell disease: observations on females with the sickle cell trait from the Manchester project, Jamaica.

Screening for haemoglobin genotype was offered to senior school students in Manchester parish in south central Jamaica to test whether this knowledge would influence choice of partner and reduce births with sickle cell disease. Over six academic years, 15,539 students, aged mostly 15-19 years, were screened with voluntary compliance rising from 56 to 92 % over this period. All subjects were given permanent genotype cards and carriers of abnormal genes were offered counselling which explained the reproductive options but avoided recommendations.

The natural history of sickle cell disease.

The term sickle cell disease embraces a group of genetic conditions in which pathology results from the inheritance of the sickle cell gene either homozygously or as a double heterozygote with another interacting gene. The spectrum of resulting conditions is therefore influenced by the geography of individual hemoglobin genes, but in most populations, the commonest genotype at birth is homozygous sickle cell (SS) disease. Because this genotype generally manifests a greater mortality, the relative proportion of sickle cell genotypes is influenced by age as well as the geographical distribution of individual genes.

Fetal growth in women with homozygous sickle cell disease: an observational study.

Objectives: To assess fetal growth and whether lower birthweight to mothers with homozygous sickle cell (SS) disease is related to maternal body composition or to clinical events in pregnancy.

Study Design: A prospective study of 41 pregnant women with SS disease and 41 women with a normal (AA) phenotype attending the antenatal clinic, University Hospital of the West Indies, Kingston, Jamaica. Maternal anthropometry, body composition and fetal sonographic measurements were assessed at 15, 25, and 35 weeks' gestation from December 2005 to April 2008.

Screening for the sickle cell gene in Gujarat, India: a village-based model.

The sickle cell gene in India reaches its highest prevalence among the tribal people, many of whom are marginalized in the Indian society, living in remote rural areas which are often in the hilly regions of the Deccan plateau. Delivery of all services including health care presents special challenges which are addressed in this study by an outreach program and a mobile clinical unit. Another concern among the tribal people, a suspicion of centrally provided services conceived as being imposed from the outside, has been addressed by the concept of the Sickle Cell Swa (self) Suraksha (protection) Abhiyan (movement), which seeks to educate tribal communities in sickle cell (SS) disease so that the request for screening emanates from the community itself.

Elevated IL-1α and CXCL10 serum levels occur in patients with homozygous sickle cell disease and a history of acute splenic sequestration.

Acute splenic sequestration (ASS) and chronic hypersplenism are common features of homozygous sickle cell (SS) disease in the first 5 years of life affecting one-third of subjects in the Jamaican Cohort Study. The risk factors are largely unknown and the current study explores a possible role of genetic factors. We have explored these in subjects who received splenectomy in the management of ASS (n=8) or chronic hypersplenism (n=9) along with age, gender, and genotype matched controls using Luminex Technology to assess 42 human cytokines/chemokines, including IL-1α and CXCL10 (IP-10).

Screening for the sickle cell gene in Chhattisgarh state, India: an approach to a major public health problem.

The aim of this study is to determine the feasibility of large-scale population screening for the sickle cell gene in high risk areas with limited resources. A programme designed to detect the sickle cell trait and sickle cell disease has screened 359,823 subjects among 2,087 (99.7%) of the villages in Raipur District, Chhattisgarh State, India between October 2007 and June 2010.

Hb S-β-thalassemia: molecular, hematological and clinical comparisons.

Clinical and hematological features are presented for 261 patients with identified β-thalassemia (β-thal) mutations. Mutations causing Hb S [β6(A3)Glu→Val]-β(0)-thal were IVS-II-849 (A>G) in 44%, frameshift codon (FSC) 6 (-A) in 14%, Hb Monroe [β30(B12)Arg→Thr] in 14%, and IVS-II-1 (G>A) in 10%. Mutations causing Hb S-β(+)-thal with 14-25% Hb A (type III) were -29 (A>G) mutation in 60%, -88 (C>T) in 22% and the polyadenylation signal site (polyA) (T>C) mutation in 14%, and in Hb S-β(+)-thal with 1-7% Hb A (type I), all had the IVS-I-5 (G>C) mutation.

One hundred years of sickle cell disease.

The first formal report of sickle cell disease occurred 100 years ago. This review traces the early historical reports, the evolution of understanding of the genetics, the molecular and chemical basis of sickle haemoglobin, and the advances made over the last 30-40 years in improving the management. Newborn screening and close follow-up, especially early in life, has significantly improved survival but these advances require resources and sophisticated infrastructure.

Retained placenta in homozygous sickle cell disease.

Objective: To document an increased prevalence of retained placenta in mothers with homozygous sickle cell disease.

Methods: A retrospective review (January 1, 1992, to December 31, 2005) at the University Hospital of the West Indies revealed 174 singleton deliveries in women with sickle cell disease who were matched by delivery date and age 1:1 with 174 mothers with normal hemoglobin phenotype. Cesarean delivery in 62 mothers (36%) with sickle cell and in 41 women with normal hemoglobin (24%) left 112 sickle cell and 133 normal hemoglobin pregnancies with spontaneous deliveries.

Albuminuria and renal function in homozygous sickle cell disease: observations from a cohort study.

Background: The glomerular filtration rate (GFR) in homozygous sickle cell (SS) disease is supranormal in childhood but falls steeply with age, often culminating in renal failure. The risk factors underlying these observations are unclear. We therefore sought to investigate the relationships between blood pressure, renal hemodynamics, and urinary albumin excretion in subjects with SS disease and matched controls with a normal AA genotype (hereinafter, controls) as a prelude to intervention studies.