Newborn screening for sickle cell disease: effect on mortality.
ABSTRACT Newborn screening for sickle cell disease has been recommended as a method of decreasing patient mortality. However, its effectiveness in accomplishing this has not been reliably measured. To help determine the effectiveness, 10 years of experience in newborn screening have been summarized. The effects of early patient enrollment in a comprehensive treatment program on long-term morbidity and mortality are reported. From 1975 to 1985, 84,663 newborns were screened regardless of race or ethnic background. Bart's hemoglobin was present in 5%, hemoglobin AS in 2.6%, and hemoglobin AC in 0.75%. Excluding Bart's, approximately 3.6% of all newborns were carriers for hemoglobinopathy. Sickle cell disease occurred in 1:951 births (58 hemoglobin SS, 25 hemoglobin FSC, three hemoglobin S-beta +-thalassemia, and three hemoglobin S-beta O-thalassemia). In addition, one in every 4,233 newborns had a clinically significant thalassemia syndrome (eight hemoglobin FE, ten hemoglobin F only, two hemoglobin H). Compared with other newborn screening programs in California, (congenital hypothyroidism, 1:3,849; phenylketonuria 1:22,474, galactosemia 1:74,103), hemoglobinopathies are the most prevalent congenital disease. Eighty-one newborns with sickle cell disease were followed for 7.2 years. Patients experienced 513 hospitalizations, including 13 episodes of sepsis with or without meningitis and ten acute sequestration crises. The overall mortality rate for patients with sickle cell anemia diagnosed in the newborn period was 1.8%. In comparison, the clinical course of 64 patients with sickle cell anemia diagnosed after 3 months of age and followed for an average of 9.4 years was analyzed. Five of these patients died. In two of these, sickle cell anemia was diagnosed at the time of the death.(ABSTRACT TRUNCATED AT 250 WORDS)
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ABSTRACT: Hemoglobinopathies are mutations resulting in abnormal globin chain structure; some have clinically significant outcomes such as anemia or reduced lifespan. Five β-globinmutations are (c.20A>T, p.E6V), (c.19G>A, p. E6K),(c.79G>A, p.E26K),(c.364G>C, p.E121Q), and(c.364G>A, p.E121K), resulting in HbS (sickle-cell hemoglobin), HbC, HbE,HbD-Los Angeles, and HbO-Arab, respectively. One α-globin mutation is (c.[207C>G or 207C>A], p.N68K), resulting in HbG-Philadelphia. HPLC-ESI-MS/MS analysis of dried-blood spot (DBS) punches from newborns extracted with a trypsin-containing solution provides greater than 90% coverage of α-, β-, and γ-globinamino acid sequences. Because the(c.20A>T, p.E6V), (c.19G>A, p. E6K), (c.79G>A, p.E26K), (c.364G>C, p.E121Q), (c.364G>A, p.E121K), and (c.[207C>G or 207C>A], p.N68K)mutations generate globinpeptides with novel amino acid sequences, detecting one of these peptides in DBS extracts is indicative of the presence of ahemoglobinopathy in the newborn. The method described here can distinguish normal β-globin peptides from the mutant HbS,HbC, HbE,HbD-Los AngelesandHbO-Arab peptides, as well as normal α-globin peptide from the mutant HbG-Philadelphia peptide, allowing the identification of unaffected heterozygotes such as HbAS, and of compound heterozygotes such as HbASG-Philadelphia. This HPLC-ESI-MS/MS analytical approach provides informationthat is not available from traditional hemoglobin analyses such as isoelectric focusing and HPLC-UV. It is also capable of determining the amino acid sequence of hemoglobinpeptides, potentially allowing the detection of numerous hemoglobinopathiesresulting from point mutations.Clinica chimica acta; international journal of clinical chemistry 06/2013; 424. DOI:10.1016/j.cca.2013.06.007 · 2.76 Impact Factor
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ABSTRACT: In 2007, the neonatal screening program in the Netherlands was expanded to include hemoglobinopathies. Newborns with sickle cell disease (SCD), as well as SCD carriers are identified. The benefit of reporting SCD carriers includes detection of more couples at risk (both parents are carriers) who can be informed about future reproductive choices, a responsibility of their general practitioner (GP). We evaluated knowledge, ideas, and actions of GPs after reporting SCD carriers and explored and analyzed potential barriers. A questionnaire study. A total of 139 GPs responded to our questionnaire (49%). Ninety GPs (90%) stated they informed parents of the test result. In only 23 cases (23%) both parents had themselves tested for hemoglobinopathies. Eighty-one GPs (64%) stated that they did not have enough clinical experience with SCD. Almost half of the GPs indicated that they did not experience any barriers in counseling patients (n=60, 48%). At the moment, the goal of the neonatal screening for SCD carriers has not been achieved as the majority of parents were not tested for hemoglobinopathies after disclosure of carrier status in their newborn. With GPs reporting few barriers in counseling parents and only indicating a lack of knowledge and clinical experience, more effort is required to provide better information to GPs to help facilitate their work.Genetic Testing and Molecular Biomarkers 05/2011; 15(10):671-5. DOI:10.1089/gtmb.2010.0232 · 1.15 Impact Factor
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ABSTRACT: Neonatal identification of sickle cell disease can significantly reduce mortality and morbidity during the first 5 years of life. During a 10-year period, 414,801 neonates were screened by isoelectric focusing. The most common variants detected were haemoglobins S, C, D and E. Two hundred and fifty of the samples tested were homozygotes or compound heterozygotes, and 6554 samples were heterozygotes for the common variants. The gene frequencies in the population tested were calculated from this data for the most common variants. They were: S, 0.0057; C, 0.0014; D(Punjab(Los Angeles)), 0.0007; E, 0.0005. Additionally, 16 babies had beta thalassaemia major and 405 had rarer variants, of which six had never previously been described. Knowledge of the distribution of these inherited diseases is useful in healthcare planning and appropriate allocation of resources, while counselling targeted at appropriate couples enables informed parental choice and may prevent disease.British Journal of Haematology 02/2001; 112(1):32-5. DOI:10.1046/j.1365-2141.2001.02512.x · 4.96 Impact Factor