Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005.

OBJECTIVES: This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England. SETTING: England. Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity. METHODS: The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/beta-thalassaemia, Hb S/D(Punjab), Hb S/O(Arab), Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satisfactory performance. RESULTS: Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500. CONCLUSION: The results from the national newborn sickle cell screening programme in England-show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.

A combination of two novel alpha globin variants Hb Bridlington (HBA1) and Hb Taybe (HBA2) resulting in severe hemolysis, pulmonary hypertension, and death.

OBJECTIVE AND IMPORTANCE: To describe two novel hemoglobin mutations that resulted in an unstable hemoglobin with a severe hemolytic phenotype. CLINICAL PRESENTATION: A patient with an unstable hemoglobin and chronic hemolysis underwent splenectomy at age 15, subsequently developing chronic thrombo-embolic pulmonary hypertension at age 27 that was ultimately fatal. INTERVENTION: DNA sequencing of the alpha globin gene revealed heterozygous inheritance of Hb Taybe, arising from a novel mutation in the HBA2 gene and Hb Bridlington, a novel HBA1 mutation. Greater disease severity is predicted by the position of the Hb Taybe mutation on the HBA2 gene (which transcribes more globin than the HBA1 gene). CONCLUSION: Splenectomy was not clearly beneficial and may have contributed to the development of pulmonary hypertension. The case favors a cautious approach when considering splenectomy for patients with Hb Taybe.

Newborn bloodspot results: predictive value of screen positive test for thalassaemia major.

AIM: There are limited published data on the performance of the percentage of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. This paper aims to analyse data derived from a national newborn bloodspot screening programme for sickle cell disease on the performance of haemoglobin A (Hb A) as a screening test for beta thalassaemia major in the newborn period. METHODS: Newborn bloodspot sickle cell screening data from 2,288,008 babies were analysed. Data reported to the NHS Sickle Cell and Thalassaemia Screening Programme in England for the period 2005 to 2012 were also reviewed to identify any missed cases (4,599,849 babies). RESULTS: Within the cohort of 2,288,008 births, 170 babies were identified as screen positive for beta thalassaemia major using a cut-point of 1.5% HbA. There were 51 identified through look-back methods and 119 prospectively identified from 4 screening laboratories. Among 119 babies with prospective data, 7 were lost to follow up and 15 were false positive results. Using a cut-off value of 1.5% Hb A as a percentage of the total haemoglobin as a screening test for beta thalassaemia major in the newborn provides an estimated sensitivity of 99% (from the look back arm of the study) with a positive predictive value of 87% (from the prospective arm of the study). Excluding infants born before 32 weeks gestation, the positive predictive value rose to 95%. CONCLUSION: A haemoglobin A value of less than 1.5% is a reliable screening test for beta thalassaemia major in the newborn period.

Advances in clinical education: a model for infectious disease training for mid-level practitioners in Uganda.

Advances in health professional education have been slow to materialize in many developing countries over the past half-century, contributing to a widening gap in quality of care compared to developed countries. Recent calls for reform in global health professional education have stressed, among other priorities, the need for approaches that strengthen clinical reasoning skills. While the development of these skills is critical to enhance health systems, little research has been carried out on the effectiveness of applying these strategies in the context of severe human resource shortages and complex disease presentations. Integrated Infectious Disease Capacity Building Evaluation (IDCAP) based at the Infectious Diseases Institute at Makerere University created a training program using current best practices in clinical education to support the development of complex reasoning skills among clinicians in rural Uganda. Over a period of 9 months, the program integrated classroom and clinic-based training approaches and measured indicators of success with particular reference to common infectious diseases. This article describes in detail the IDCAP approach to integrating advances in health professional education theory in the context of an overburdened, inadequately resourced primary health care system; results from the evaluation are expected in 2012.

Hb Leeds [beta56(D7)Gly-->Cys]: a new hemoglobin that aggravates anemia in a child with beta(0)-thalassemia trait.

A novel beta chain variant found in combination with beta(0)-thalassemia (thal) was identified in a male infant by electrospray ionization mass spectrometry (ESI-MS). Analysis of the infant's denatured blood and a 30 min. tryptic digest of his blood identified the mutation as beta56(D7)Gly-->Cys, which was confirmed by tandem mass spectrometry (MS/MS). We have named this new variant Hb Leeds. The infant's parents, resident in Yorkshire, UK, but originally from Pakistan, were found to have beta(0)-thalassemia (thal) trait (mother) and Hb Leeds trait (father). Hematological data on the infant's parents and siblings are given. Hb Leeds trait was also found in three unrelated Pakistani adults living in the same area of Yorkshire. Hb Leeds trait in adults appears to have few clinical manifestations, but when combined with beta(0)-thal it led to a more severe anemia in the infant than in the corresponding thalassemic trait in his mother.