Subject(s)
Anemia, Sickle Cell/genetics , Carrier Proteins/genetics , Fetal Hemoglobin/genetics , GTP-Binding Proteins/genetics , Genes, myb/genetics , HSP70 Heat-Shock Proteins/genetics , Nuclear Proteins/genetics , Peptide Elongation Factors/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Anemia, Sickle Cell/diagnosis , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Repressor Proteins , Severity of Illness IndexABSTRACT
BACKGROUND: Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India. METHODS AND FINDINGS: Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle ß-thalassemia (S-ß thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS-뫧 thalassemia-1, HbSD disease-2, HbE traits-5, ß-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies. CONCLUSION: A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations.
Subject(s)
Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/drug therapy , Hydroxyurea/therapeutic use , Neonatal Screening , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/mortality , Antisickling Agents/therapeutic use , Child, Preschool , Female , Heterozygote , Homozygote , Humans , India/epidemiology , Infant , Infant, Newborn , Male , Phenotype , Pregnancy , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Sickle cell disease is a major health burden in India. The aim of the study was to compare the diagnostic utility of two different approaches on automated high performance liquid chromatography (HPLC) for newborn screening for sickle cell disorders and other haemoglobinopathies in India. METHODS: Newborn babies of sickle heterozygous mothers were tested by HPLC using two different kits, the ß-thal short kit, which is routinely used for screening for haemoglobinopathies in most laboratories, and the sickle cell short kit which is specific only for neonatal samples. Confirmation of the sickle and α genotypes was done by molecular analysis. RESULTS: Of the 601 babies tested, 276 were normal, 284 were sickle heterozygous and 41 were sickle homozygous using the ß-thal short kit. Using the sickle cell short kit, a discrepancy was seen in one newborn sample where a normal baby was identified as a sickle heterozygous baby. α-Genotyping was done in 42 babies and 16 of them had α gene deletions. The presence of α thalassaemia could be suspected in 15 of these 16 babies based on a spike at the start of the chromatogram using the ß-thal short kit. In comparison, using the sickle cell short kit the diagnosis of α thalassaemia was difficult based on the percentage of the FAST peak. Further, other rare α chain Hb variants were also missed. CONCLUSIONS: The ß-thal short kit was more versatile than the sickle cell short kit for screening for haemoglobinopathies in newborns in our population.
