RESUMEN

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.

RESUMEN

OBJECTIVE: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study. METHODS: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status. RESULTS: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented. CONCLUSION: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.

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OBJETIVO: Comparar los rasgos clínicos de la anemia de células falciformes homocigóticas (SS) en los haplotipos Bantú y Benin en un estudio transversal de 115 pacientes ugandeses que asisten a la Clínica de la anemia de células falciformes en el Hospital de Mulago, Kampala, Uganda, con 311 pacientes en un estudio de cohorte jamaicano. MÉTODOS: El estudio conllevó la comparación de los rasgos clínicos y hematológicos con referencia especial a los determinantes genéticos de la severidad, incluyendo los niveles de la hemoglobina fetal, haplotipos del gen de la globina beta, y el estado de la alfa talasemia. RESULTADOS: El haplotipo Bantú dio cuenta del 94% de los cromosomas HbS en los pacientes ugandeses, en tanto que los haplotipos Benin dieron cuenta del 76% de los cromosomas de HbS en Jamaica. Los pacientes de Uganda presentaron una probabilidad marginalmente mayor de alfa talasemia, tenían niveles similares de hemoglobina total y hemoglobina fetal, pero en cambio presentaban conteos más altos de reticulocitos así como niveles mayores de bilirrubina total, en correspondencia con una mayor hemólisis. Los pacientes ugandeses presentaban menor ulceración de las piernas y priapismo, pero el modo de presentación clínica, la prevalencia de dactilitis, los rasgos de dolor óseo, y el grado de retraso en el desarrollo sexual, evaluado por la menarquia, fueron similares en todos los grupos. Los pacientes de Uganda se caracterizaron comúnmente por una historia de episodios de anemia, pobremente documentados. CONCLUSIÓN: Los rasgos clínicos y hematológicos del haplotipo Bantú en Uganda fueron considerablemente similares al haplotipo Benin en Jamaica, salvo por una menor presencia de ulceración de las piernas y priapismo, así como posiblemente mayor hemólisis entre los sujetos de Uganda. Los episodios de anemia en Uganda fueron tratados empíricamente mediante transfusión, a menudo sin un diagnóstico claro. Se necesita una mejor documentación - incluyendo conteos de reticulocitos - así como observaciones del tamaño del bazo, a fin de desarrollar modelos de cuidado apropiados.

Asunto(s)

Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven , Anemia de Células Falciformes/genética , Hemoglobina Falciforme/genética , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Bilirrubina/sangre , Estudios de Cohortes , Estudios Transversales , Hemoglobina Fetal/análisis , Haplotipos , Hemoglobina Falciforme/clasificación , Homocigoto , Jamaica , Dolor Musculoesquelético/etiología , Priapismo/etiología , Pubertad Tardía/etiología , Reticulocitos/citología , Úlcera Cutánea/etiología , Esplenomegalia/diagnóstico , Esplenomegalia/epidemiología , Uganda , Talasemia alfa/complicaciones , Globinas beta/clasificación , Globinas beta/genética

RESUMEN

OBJECTIVE: To compare the haematological and clinical features of homozygous sickle cell (SS) disease in Bantu and Benin haplotypes in a cross-sectional study of 115 Ugandan patients attending the Sickle Cell Clinic at Mulago Hospital, Kampala, Uganda, with 311 patients in the Jamaican Cohort Study METHODS: This involved comparison of clinical features and haematology with special reference to genetic determinants of severity including fetal haemoglobin levels, beta-globin haplotype and alpha thalassaemia status. RESULTS: The Bantu haplotype accounted for 94% of HbS chromosomes in Ugandan patients and the Benin haplotype for 76% of HbS chromosomes in Jamaica. Ugandan patients were marginally more likely to have alpha thalassaemia, had similar total haemoglobin and fetal haemoglobin levels but had higher reticulocyte counts and total bilirubin levels consistent with greater haemolysis. Ugandan patients had less leg ulceration and priapism, but the mode of clinical presentation, prevalence of dactylitis, features of bone pain and degree of delay in sexual development, assessed by menarche, were similar in the groups. In Ugandan patients, a history of anaemic episodes was common but these were poorly documented. CONCLUSION: The haematological and clinical features of the Bantu haplotype in Uganda were broadly similar to the Benin haplotype in Jamaica except for less leg ulceration and priapism and possibly greater haemolysis among Ugandan subjects. Anaemic episodes in Uganda were treated empirically by transfusion often without a clear diagnosis; better documentation including reticulocyte counts and observations on spleen size is necessary to evolve appropriate models of care.

Asunto(s)

Anemia de Células Falciformes/genética , Hemoglobina Falciforme/genética , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Bilirrubina/sangre , Niño , Preescolar , Estudios de Cohortes , Estudios Transversales , Femenino , Hemoglobina Fetal/análisis , Haplotipos , Hemoglobina Falciforme/clasificación , Homocigoto , Humanos , Lactante , Jamaica , Masculino , Persona de Mediana Edad , Dolor Musculoesquelético/etiología , Priapismo/etiología , Pubertad Tardía/etiología , Reticulocitos/citología , Úlcera Cutánea/etiología , Esplenomegalia/diagnóstico , Esplenomegalia/epidemiología , Uganda , Adulto Joven , Talasemia alfa/complicaciones , Globinas beta/clasificación , Globinas beta/genética

RESUMEN

Earlier reports on homozygous sickle cell (SS) disease have been biased by severely affected cases. The Jamaican clinic which seeks to avoid such bias has 102 patients surviving beyond 60 years. The objective of this study was to examine the features of elderly cases and assess factors determining survival and the behaviour of this disease with advancing age. A retrospective review of all cases and prospective assessment in survivors was conducted at The Sickle Cell Clinic at the University of the West Indies, Kingston, Jamaica previously operated by the MRC Laboratories. All patients with SS disease born prior to December 31, 1943 who would, by January 2004, have passed their 60th birthday were traced and their current status ascertained. The molecular and clinical features were assessed and observations on the clinical behaviour of the disease and of haematology and biochemistry are presented. Of the 102 patients, 58 had died, four had emigrated and 40 were alive, resident in Jamaica and aged 60-87 years. Survival was associated with female gender and higher foetal haemoglobin but not with alpha-thalassaemia or beta-globin haplotype. A tendency to familial clustering among elderly survivors did not reach statistical significance. Painful crises ameliorated with age and there was a benign course in pregnancy. Mean haemoglobin levels fell with age and were generally associated with rising creatinine levels indicating the importance of renal failure. Elderly survivors present some features of intrinsic mildness but also manifest age-related amelioration of painful crises and falling haemoglobin levels from progressive renal damage.

Asunto(s)

Anemia de Células Falciformes , Anciano , Anciano de 80 o más Años , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/mortalidad , Femenino , Hemoglobina Fetal , Homocigoto , Humanos , Jamaica/epidemiología , Estudios Longitudinales , Masculino , Embarazo , Complicaciones Hematológicas del Embarazo , Estudios Retrospectivos , Globinas beta/genética

RESUMEN

The roles of genetic and non-genetic factors in the haematology, growth and clinical features of sickle cell disease have been studied in nine identical twin pairs (six homozygous sickle cell disease, three sickle cell-haemoglobin C disease). A comparison group of 350 age-gender matched sibling pairs, selected to have an age difference of <5 years, was used for assessing the concordance of numerical data. Attained height, weight at attained height, fetal haemoglobin, total haemoglobin, mean cell volume, mean cell haemoglobin and total bilirubin levels showed significantly greater correlation in identical twins than in siblings. Twins showed similarities in the prevalence and degree of splenomegaly, susceptibility to priapism, and in onset of menarche, but other clinical complications were discordant in prevalence and severity. These findings suggest that physical growth and many haematological characteristics are subject to genetic influences, but that non-genetic factors contribute to the variance in disease manifestations.

Asunto(s)

Anemia de Células Falciformes/genética , Anemia de Células Falciformes/patología , Adolescente , Adulto , Anemia de Células Falciformes/complicaciones , Niño , Preescolar , Femenino , Genotipo , Crecimiento y Desarrollo , Pruebas Hematológicas , Humanos , Masculino , Fenotipo , Proyectos Piloto , Hermanos

RESUMEN

Oxygen saturation was determined by pulse oximetry in a representative sample of Jamaican patients with steady-state sickle cell disease in a cohort study from birth. There were 220 with homozygous sickle cell (SS) disease and 142 with sickle cell-haemoglobin C (SC) disease aged 9-18 years, and 122 with a normal haemoglobin (AA) genotype aged 15-18 years. Pulse oximetry (SpO2) values were lower in SS disease (mean [95% confidence interval], 92.5 [92.0-93.0]) than in SC disease (96.7[96.5-96.9]) or AA controls (97.1 [96.8-97.3]). Inhalation of 100% oxygen in SS patients with O2 saturations below 90% consistently increased saturation to 99-100%. In SS disease, SpO2 correlated positively with haemoglobin and fetal haemoglobin and negatively with reticulocyte counts but not with MCHC, MCV or bilirubin level. Mean SpO2 in SS subjects with a normal alpha globin gene complement (mean [SD], 91.7 [3.9]%) was lower than in heterozygotes (93.4 [4.0]%) or homozygotes (96.1 [3.0]%) for alpha+ thalassaemia, the effects of alpha-thalassaemia not being explained by differences in haemoglobin or MCHC. In SS disease, SpO2 levels were not associated with age (within this age range), sex, number of sick clinic visits or number of hospital admissions. Higher SpO2 levels were associated with greater height and weight, more frequent painful crises and less frequent acute chest syndrome, but these associations were not significant after adjustment for haemoglobin level. Desaturation is common in steady-state SS disease and knowledge of the individual's steady-state value may be important in the interpreting low values during acute complications.

Asunto(s)

Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/metabolismo , Oximetría , Adolescente , Factores de Edad , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/metabolismo , Dolor en el Pecho/sangre , Dolor en el Pecho/metabolismo , Niño , Estudios de Cohortes , Femenino , Genotipo , Crecimiento/fisiología , Humanos , Pruebas de Inteligencia , Masculino , Oximetría/normas , Oximetría/estadística & datos numéricos , Oxígeno/administración & dosificación , Oxígeno/sangre , Valores de Referencia , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Factores Sexuales

RESUMEN

AIMS: (1) To estimate the proportion of subjects with homozygous sickle cell disease who have a benign clinical course, and (2) to assess factors that may be predictive of benign disease. MATERIAL: Subjects (n = 280) were participants in a longitudinal cohort study of sickle cell disease. They were classified as benign or control based on clinical history from birth to age 13 years old. Associations with growth, hematology, and an index of social status were investigated. RESULTS: Benign disease occurred in 43 (15%) patients. Neither growth nor social status were related to benign disease. There were only two statistically independent associations: alpha thalassemia status and average steady state fetal hemoglobin (HbF). Patients with a normal complement of alpha globin genes were 2.2 (1.0, 4.9) times more likely to have benign disease than those with gene deletion, and were less likely to have frequent painful crises, dactylitis, and bone necrosis. The odds of having benign disease were 1.09 (1.02, 1.17) times higher for each unit increase in HbF, and 44% of subjects with HbF in the top decile (HbF > 13.8%) of the distribution had benign disease. There was no evidence for a threshold effect of high HbF on benign disease. CONCLUSION: A benign clinical course of sickle cell disease may occur in Jamaica and is associated with a normal alpha globin gene complement, and high levels of HhF. Ability to predict benign disease at birth is limited.

Asunto(s)

Rasgo Drepanocítico/epidemiología , Rasgo Drepanocítico/genética , Adolescente , Niño , Preescolar , Estudios de Cohortes , Hemoglobina Fetal/análisis , Eliminación de Gen , Globinas/análisis , Homocigoto , Humanos , Lactante , Recién Nacido , Jamaica/epidemiología , Pronóstico , Clase Social

RESUMEN

OBJECTIVE: To investigate the role of haematological indices, socioeconomic status, and morbidity in prepubertal growth in homozygous sickle cell (SS) disease. METHOD: Height, weight, and haematology were serially recorded in a cohort study of 315 children with SS disease from birth to 9 years at the sickle cell clinic of the University Hospital of the West Indies, Kingston, Jamaica. RESULTS: Height increment between 3 and 9 years correlated positively with total haemoglobin at age 7 years in boys but not girls. Attained height and weight at age 7 years correlated positively with haemoglobin and fetal haemoglobin in boys but not girls. Only the correlation between haemoglobin and weight showed a significant gender difference. Partial correlation analysis suggested that the effect of haemoglobin was accounted for by the effect of fetal haemolglobin and further analysis indicated that height correlated with F reticulocyte count (a measure of fetal haemoglobin production) in both sexes but not with the ratio of F cells to F reticulocytes (a measure of F cell enrichment). Growth was not significantly related to mean red cell volume, proportional reticulocyte count, alpha thalassaemia, socioeconomic status, or morbidity. CONCLUSION: A high concentration of fetal haemoglobin in boys with SS disease is associated with greater linear growth. It is postulated that in boys, low concentrations of fetal haemoglobin increase haemolysis and hence metabolic requirements for erythropoiesis, putting them at greater risk of poor growth. Differences in the relationship of haematology and growth between boys and girls with SS disease dictate that future analyses of growth take gender into account.

Asunto(s)

Anemia de Células Falciformes/fisiopatología , Crecimiento/fisiología , Hemoglobinas/análisis , Anemia de Células Falciformes/sangre , Estatura/fisiología , Peso Corporal/fisiología , Estudios de Cohortes , Femenino , Hemoglobina Fetal/análisis , Homocigoto , Humanos , Recién Nacido , Masculino , Factores Sexuales , Clase Social

RESUMEN

High total haemoglobin levels in homozygous sickle cell (SS) disease are a risk factor for painful crises, avascular necrosis of the femoral head, proliferative sickle retinopathy, and the acute chest syndrome. Since lowering the haemoglobin level may ameliorate these features, understanding the determinants of total haemoglobin may be of practical importance. A range of possible determinants including red cell characteristics, reticulocytes, serum iron, transferrin saturation, serum ferritin, alpha thalassaemia status, red cell mass and plasma volume, oxygen affinity, red cell survival, transferrin receptor and erythropoietin levels have been measured in 62 patients selected to provide a range of total haemoglobin and fetal haemoglobin levels. There were weak negative associations of haemoglobin with mean cell volume and mean cell haemoglobin concentration, strong negative associations with proportional reticulocyte counts, oxygen affinity, plasma volume, serum transferrin receptors, and erythropoietin levels and strong positive associations with red cell mass. Weighted analysis suggested that the statistically independent determinants of haemoglobin level were alpha thalassaemia, sex, red cell mass/body weight, plasma volume/body weight, fetal haemoglobin, and red cell count. The apparent contributions of red cell survival, P50, reticulocyte count, serum transferrin receptor and erythropoietin levels were explained by the effects of these other variables. The independent determinants as a group explained 91% of the variation in haemoglobin level.

Asunto(s)

Anemia de Células Falciformes/sangre , Hemoglobinas/análisis , Adulto , Volumen Sanguíneo , Envejecimiento Eritrocítico , Índices de Eritrocitos , Femenino , Hemoglobina Fetal/análisis , Humanos , Hierro/sangre , Masculino , Recuento de Reticulocitos , Transferrina/análisis , Talasemia alfa/sangre

RESUMEN

Homozygous alpha+ thalassaemia (alpha-/alpha-) ameliorates some of the clinical manifestations of homozygous sickle cell (SS) disease but its effect on retinal complications remains unknown. This has been assessed by visual examination and fluorescein angiography in 39 subjects with SS disease and homozygous alpha+ thalassaemia and in 39 age/sex matched controls with SS disease but with a normal alpha globin genotype (alpha alpha/alpha alpha). The results indicate that homozygous alpha+ thalassaemia reduces the extent of peripheral retinal vessel closure but has no apparent effect on the frequency of proliferative sickle retinopathy.

Asunto(s)

Anemia de Células Falciformes/complicaciones , Enfermedades de la Retina/etiología , Talasemia alfa/complicaciones , Adolescente , Adulto , Factores de Edad , Anciano , Anemia de Células Falciformes/genética , Femenino , Angiografía con Fluoresceína , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales

RESUMEN

Haematological indices have been studied in 181 patients with homozygous sickle cell (SS) disease aged 40-73 years. Cross-sectional analyses in 5-year age bands indicated age-related decreases in HbF (males only), total haemoglobin and platelet counts. Longitudinal studies within individuals confirmed the downward age-related trend in haemoglobin and platelets and also revealed a falling reticulocyte count, most significant when expressed as absolute values. Total nucleated cells also fell although the decline was significant only in females. These observations are consistent with a progressive bone marrow failure which is not explained by the commonly occurring renal impairment in older SS patients since the changes persisted in analyses confined to patients with normal creatinine levels. The mechanism of this bone marrow failure is currently unknown.

Asunto(s)

Anemia de Células Falciformes/sangre , Adulto , Anciano , Envejecimiento/sangre , Anemia de Células Falciformes/complicaciones , Estudios Transversales , Femenino , Hemoglobina Fetal/análisis , Hemoglobinas/análisis , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Factores Sexuales , Talasemia/complicaciones

RESUMEN

The effects of alpha thalassaemia on sickle cell-beta zero thalassaemia have been studied by comparing haematological and clinical features in four subjects homozygous for alpha thalassaemia 2 (2-gene group), 27 heterozygotes (3-gene group), and 55 with a normal alpha globin gene complement (4-gene group). Alpha thalassaemia was associated with significantly higher haemoglobin levels and lower reticulocyte counts independent of the presence of splenomegaly. Contrary to expectation, alpha thalassaemia was associated with small but significant increases in mean cell volume and mean corpuscular haemoglobin concentration. Splenomegaly at age 5 years and episodes of acute splenic sequestration were significantly more frequent in the 4-gene group. There were no significant differences in painful crises, acute chest syndrome, or other clinical features.

Asunto(s)

Anemia de Células Falciformes/sangre , Talasemia/sangre , Adolescente , Adulto , Anemia de Células Falciformes/genética , Niño , Preescolar , Recuento de Eritrocitos , Índices de Eritrocitos , Femenino , Genes , Globinas/genética , Humanos , Masculino , Persona de Mediana Edad , Reticulocitos , Esplenomegalia , Talasemia/genética

RESUMEN

The gene frequencies of abnormal haemoglobins have been determined in a group of 100,000 Jamaican newborns screened over a period of 8 1/2 years. The population is predominantly of West African origin and the survey represents approximately one quarter of all island deliveries within the period of the study. The common beta globin chain abnormalities beta s and beta c occurred with gene frequencies of 0.055 and 0.019 respectively; beta thalassaemia was relatively rare. In contrast, alpha thalassaemia was quite common, occurring with a gene frequency of 0.183. In addition to these common abnormalities, the frequencies of 256 rare abnormal haemoglobins are described. This survey thus represents a complete and accurate documentation of the alpha and beta globin variants that occur in the Jamaican population.

Asunto(s)

Frecuencia de los Genes , Hemoglobinas Anormales/genética , Humanos , Recién Nacido , Jamaica , Fenotipo , Rasgo Drepanocítico/epidemiología , Rasgo Drepanocítico/genética , Talasemia/epidemiología , Talasemia/genética

RESUMEN

alpha Thalassemia modifies the hematologic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and bilirubin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of children with SS disease has afforded an opportunity to study the hematologic indices in nine children homozygous for alpha thalassemia 2 (two-gene group), 90 children heterozygous for alpha thalassemia 2 (three-gene group), and 167 children with a normal alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for alpha thalassemia status at birth.

Asunto(s)

Anemia de Células Falciformes/complicaciones , Talasemia/complicaciones , Factores de Edad , Anemia de Células Falciformes/sangre , Niño , Preescolar , Recuento de Eritrocitos , Volumen de Eritrocitos , Hemoglobina Fetal/análisis , Genotipo , Humanos , Lactante , Jamaica , Reticulocitos/análisis , Talasemia/sangre

RESUMEN

Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period. The age at first attack ranged from 3 months to 6 years. Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.225 by 2 years, and 0.265 by 3 years, and 0.297 by 5 years of age. Thirteen events were fatal, 11 during the first attack, and all before transfusion could be instituted. Recurrences occurred in 49% of survivors of the first attacks, and there were diminishing intervals between subsequent events. Respiratory symptoms were associated with 52 of 132 events, but bacterial isolates on blood culture were less frequent, and ASS was not prevented by pneumococcal vaccine or penicillin prophylaxis. A high fetal hemoglobin level protected against attacks of ASS. A parental education program aimed at early diagnosis of ASS was followed by an increase in the incidence rate for ASS from a mean of 4.6 per 100 patient-years to 11.3 per 100 patient-years, probably reflecting increased awareness of the complication. During the same periods, the fatality rate fell from 29.4 per 100 events to 3.1 per 100 events. The improvement in outcome is likely to have resulted from improvement in medical management and earlier detection of ASS.

Asunto(s)

Anemia de Células Falciformes/complicaciones , Enfermedades del Bazo/complicaciones , Enfermedad Aguda , Niño , Preescolar , Femenino , Humanos , Masculino , Enfermedades del Bazo/diagnóstico , Enfermedades del Bazo/mortalidad

RESUMEN

The pattern of initial clinical symptoms and signs developing in a representative sample of 305 children with homozygous sickle cell (SS) disease diagnosed at birth was analyzed. Specific symptoms were present by age 6 months in 6% of the group, and had developed by the first to eighth birthdays in 32%, 61%, 78%, 86%, 90%, 92%, 94%, and 96%, respectively. Inclusion of nonspecific symptoms in the analysis led to earlier recognition by a mean of 3 months in the first year and by a mean of approximately 1 year between the ages of 2 and 4 years. Dactylitis was the most common initial symptom, noted in 40% of the group overall and in 50% in the first 2 years. Painful crisis was the first symptom in more than one fourth of the patients and was the most frequent symptom after the age of 2 years. Acute splenic sequestration led to presentation in one-fifth of the group overall and in one third of patients younger than 2 years. The most common nonspecific symptom was pneumonia. There was a significant trend of earlier presentation in children with low fetal hemoglobin levels. The age at presentation did not appear to be affected by alpha-thalassemia status.

Asunto(s)

Anemia de Células Falciformes/fisiopatología , Homocigoto , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/mortalidad , Niño , Preescolar , Hemoglobina Fetal/análisis , Humanos , Lactante , Dolor/fisiopatología , Talasemia/fisiopatología

RESUMEN

Ten patients with sickle cell (SS) disease from a Jamaican family were found to have unusually high levels of haemoglobin F for this population. Each of them has inherited one sickle cell gene on a chromosome characterized by an arrangement of restriction fragment length polymorphisms (haplotype) which is very rare in the Jamaican population. Genetic analysis of the family suggests that there is a determinant linked to the beta-globin gene cluster, characterized by this haplotype, which is responsible for increased haemoglobin F production in response to anaemia. Interestingly this particular haplotype appears to be common in patients with SS disease in eastern Saudi Arabia in whom a high level of haemoglobin F is the rule rather than the exception. Hence it is possible that this haplotype (++-++) acts as a genetic marker for elevated levels of haemoglobin F in sickle cell disease.

Asunto(s)

Anemia de Células Falciformes/genética , Hemoglobina Fetal/genética , Marcadores Genéticos , Rasgo Drepanocítico/genética , Femenino , Haploidia , Humanos , Jamaica , Masculino , Linaje , Arabia Saudita

RESUMEN

Haematological indices were studied from birth to 9 years in a representative sample of 195 children with a normal haemoglobin (AA) genotype subdivided according to the number of alpha globin genes. These were 5 homozygotes for alpha-thalassaemia 2 (two-gene group), 60 heterozygotes for alpha-thalassaemia 2 (three-gene group), and 130 with a normal alpha globin gene complement (four-gene group). HbF and HbA2 showed no differences between the groups. Compared to the four-gene group, the three-gene group tended to have significantly lower levels of total haemoglobin, MCHC, MCV, and MCH, and higher levels of red cell count. These differences became apparent with increasing age in the order of MCV, RBC, MCHC, and total haemoglobin. The data suggested that haematological differences were more marked in the two-gene group but with the small numbers available, the differences were not significant.

Asunto(s)

Talasemia/sangre , Niño , Preescolar , Femenino , Hemoglobina Fetal/metabolismo , Genotipo , Globinas/genética , Hemoglobina A2/metabolismo , Heterocigoto , Homocigoto , Humanos , Lactante , Jamaica , Masculino , Talasemia/genética

RESUMEN

Restriction site polymorphisms of the beta globin gene cluster of 244 Jamaican beta S chromosomes have been studied. Various patterns of restriction site polymorphisms (haplotypes) both 5' and 3' to the beta gene have been found. These two groups of haplotypes were found to be non-randomized with respect to each other. This is in contrast to normal beta A chromosomes where the 5' and 3' haplotypes are randomized. These findings together with the large number (18) of different beta S haplotypes found indicate that the beta S mutation probably has multiple origins.

Asunto(s)

Anemia de Células Falciformes/genética , Globinas/genética , Polimorfismo Genético , Rasgo Drepanocítico/genética , Enzimas de Restricción del ADN , Genes , Humanos , Jamaica , Mutación

RESUMEN

We have studied seven Jamaican Negro families in whom the genes for alpha thalassaemia and the sickle cell mutation (betas) were independently segregated. Using a combination of techniques we identified two alpha thalassaemia phenotypes which resemble the severe (alpha thalassaemia 1) and mild (alpha thalassaemia 2) determinants previously described in Orientals. This study has enabled us to clearly correlate the phenotype of alpha thalassaemia with the genotype in this population. Furthermore, since in each family alpha thalassaemia was present in association with the gene for the sickle cell mutation we have determined the proportion of Hb S in the peripheral blood of individuals with the alpha alpha/alpha alpha, -alpha/alpha alpha and -alpha/-alpha genotype who are also heterozygous for the betas mutation. Genetic analysis in these families shows that in each case subjects with the alpha thalassaemia 1 phenotype are homozygous for the alpha thalassaemia 2 defect (-alpha/-alpha). We have found no instances of the genotype --/alpha alpha in this population which may explain the rarity of the severe alpha thalassaemia syndromes in Jamaica. Restriction mapping data in the alpha thalassaemia 2 homozygotes from this population shows that the (-alpha/) haplotype results from a deletion of one of the linked pair of alpha globin genes and that this has probably arisen by an unequal crossover between non-homologous alpha genes.

Asunto(s)

Población Negra , Hemoglobina Falciforme/análisis , Talasemia/genética , Mapeo Cromosómico , ADN/sangre , Femenino , Genotipo , Heterocigoto , Homocigoto , Humanos , Jamaica , Masculino , Linaje , Fenotipo , Talasemia/sangre