Co-inheritance of triplicated α-genes can alter the clinical and hematological phenotypes of β-thalassemias. We evaluated the phenotypic diversity and transfusion requirements in β-thalassemia heterozygotes, homozygotes, and normal individuals with associated α-gene triplication. Clinical and hematological evaluation was done and the β-thalassemia mutations characterized by a covalent reverse dot blot hybridization/amplification refractory mutation system. Alpha-globin gene triplication was assessed by multiplex PCR. During the last 2.5 years, 181 β-thalassemia patients and β-thalassemia carriers with an unusual clinical presentation were referred to us for screening for the presence of associated α-globin gene triplication. Twenty-nine of them had associated α-gene triplication (3 β-thalassemia homozygotes or compound heterozygotes and 26 β-thalassemia heterozygotes). One β-thalassemia compound heterozygote [IVS 1-5 (G → C) + CD 41/42 (-CTTT)] was anemic at birth and required blood transfusions unusually early by 6 weeks of age. The second patient (4.5 years) was also clinically severe and became transfusion dependent in spite of having one mild β-thalassemia mutation [Capsite +1 (A → C)]. The third case (3.5 years) who was homozygous for a mild β-gene mutation [-88 (C → T)] with α gene triplication was untransfused. The 26 β-thalassemia heterozygotes with associated triplicated α-genes presented variably, with a β-thalassemia intermedia-like presentation. While screening the family members of all these cases, we found another 10 β-thalassemia heterozygotes and 9 normal individuals with α-globin gene triplication; however, all of them were asymptomatic. Beta-thalassemia carriers, homozygotes, and compound heterozygotes with an unusual presentation should be screened for the possible presence of associated α-globin gene triplication which could influence the clinical and hematological presentation.

There is limited data on the incidence of sickle cell anemia in Central India; we therefore conducted a study to estimate the incidence of this disease in Central India. Mothers who delivered a live baby at the Government Medical College, Nagpur, India were screened for the presence of the sickle cell hemoglobin {Hb S: [β6 (A3) Glu→Val, GAG>GTG]} using the solubility test within 48 hours of delivery. Infants of mothers who showed the presence of Hb S then underwent Hb analysis by high performance liquid chromatography (HPLC). A total of 8243 mothers was screened, 1178 of whom were positive. One thousand, one hundred and sixty-two infants of mothers with a positive solubility test underwent Hb analysis by HPLC; 530 infants were normal, while 536 were heterozygous for Hb S (sickle cell trait), 88 babies were homozygous for Hb S (sickle cell anemia), while another eight babies had other Hb abnormalities. The incidence of sickle cell anemia was highest in the Scheduled caste group (1:50). We concluded that the incidence of sickle cell anemia is high in central India.

BackgroundSickle 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 FindingsPregnant 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 β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS -δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-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.ConclusionA 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.

Newborn screening for sickle cell disorders also enabled us to identify three α globin chain variants. Two babies who inherited Hb Fontainebleau and Hb O Indonesia along with Hb S had reduced Hb levels at birth and need to be followed up.