Αlpha-thalassemia: A practical overview.

α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and ß globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.

Thalassemia Intermedia: Chelator or Not?

Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes ß-TI hemoglobin, E/ß-thalassemia and hemoglobin H (HbH) disease. Due to the availability of iron chelation therapy, the life expectancy of thalassemia major (TM) patients is now close to that of TI patients. Iron overload is noted in TI due to the increasing iron absorption from the intestine. Questions are raised regarding the relationship between iron chelation therapy and decreased patient morbidity/mortality, as well as the starting threshold for chelation therapy. Searching all the available articles up to 12 August 2022, iron-chelation-related TI was reviewed. In addition to splenectomized patients, osteoporosis was the most common morbidity among TI cases. Most study designs related to ferritin level and morbidities were cross-sectional and most were from the same Italian study groups. Intervention studies of iron chelation therapy included a subgroup of TI that required regular transfusion. Liver iron concentration (LIC) ≥ 5 mg/g/dw measured by MRI and ferritin level > 300 ng/mL were suggested as indicators to start iron chelation therapy, and iron chelation therapy was suggested to be stopped at a ferritin level ≤ 300 ng/mL. No studies showed improved overall survival rates by iron chelation therapy. TI morbidities and mortalities cannot be explained by iron overload alone. Hypoxemia and hemolysis may play a role. Head-to-head studies comparing different treatment methods, including hydroxyurea, fetal hemoglobin-inducing agents, hypertransfusion as well as iron chelation therapy are needed for TI, hopefully separating ß-TI and HbH disease. In addition, the target hemoglobin level should be determined for ß-TI and HbH disease.

Thalassemia in Indonesia.

Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry ß-thalassemia (ß-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with ß-thal major (ß-TM) each year. At present, the cornerstone of treatment for ß-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia.

Newborn Screening and Clinical Profile of Children With Sickle Cell Disease in a Tribal Area of Gujarat.

OBJECTIVE: To present the result of newborn sickle cell disease (SCD) screening and clinical profile of SCD newborns in a tribal area of Gujarat. METHODS: We screened all newborns of sickle cell trait (SCT) and SCD mothers for SCD using high-performance liquid chromatography (HPLC) within two days of birth at a secondary care hospital in a tribal area in Gujarat from 2014 to 2019. Newborns with SCD were registered under an information technology based platform for hospital-based comprehensive care. Neonates were followed prospectively every 3 months. If they missed the clinic visit, a medical counsellor visited them at home to collect the required information. RESULTS: Out of 2492 newborns screened, 87 (3.5%) were diagnosed with SCD. Among the 67 newborns screened for alpha-thalassemia deletion, 64 (95.4%) of babies had alpha-thalassemia deletion. We recorded total 554 clinic visits over the period of 221.5 person-years. The rates of acute febrile illness, painful crisis, hospitalization and severe anemia were 42.9, 14.9, 14.9 and 4.5 per 100 person-year, respectively. Two deaths were recorded, and 5 babies (5.7%) had severe SCD. CONCLUSION: We found a high prevalence of alpha thalassemia deletion among newborn SCD cohort in tribal area of Gujarat, and 70% babies had atleast one clinical complication on follow-up.

The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

INTRODUCTION: Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. METHODS: This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. RESULTS: One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. CONCLUSIONS: The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

Utilization of Discriminant Formulas in the Differentiation of Alpha Thalassemia, Beta Thalassemia, and Iron Deficiency in Premarital Setting.

BACKGROUND: Iron deficiency and thalassemia are two commonly encountered microcytic and hypochromic anemias. The primary objective was to find the best discriminant formula between alpha thalassemia and iron deficiency to be used in premarital screening centers. The secondary objective, was to find cutoff values that might differentiate alpha thalassemia, beta thalassemia, and iron deficiency collectively. METHODS: A total of 224 females divided into four groups (normal, alpha thalassemia, beta thalassemia, and iron deficiency) were recruited in this study after carrying out complete blood count, hemoglobin electrophoresis, serum ferritin, and molecular analysis. Based upon the laboratory data, 26 discriminant formulas (DF) were applied to differentiate alpha thalassemia, beta thalassemia, and iron deficiency anemia. Receiver Operating Characteristic (ROC) curve was constructed and sensitivity, specificity, and Youden's index were determined. RESULTS: In this study, Shine and Lal, Ehsani, Telissani, Sirachainan, Hisham, Kandhro 2, and Mantos indexes showed 100% sensitivity, specificity, Youden's index, and 1.00 AUC for differentiating alpha thalassemia from iron deficient group. Formulas that showed best sensitivity and specificity (100%) in the discrimination of beta thalassemia and iron deficiency were Mentzer, Shine & Lal, Sarivastava & Bevington, and Sirachainan index (AUC 1.00). AUC of Mentzer index was lower (0.988 vs. 1.00) in differentiating alpha thalassemia and iron deficiency than beta thalassemia and iron deficiency. CONCLUSIONS: Almost all discriminant formulas can be utilized for the prediction of microcytic anemia in a premarital setup after excluding beta thalassemia; however, further confirmation is mandatory for genetic counselling and iron supplementation. Furthermore, Bordbar, Kerman index I, and Huber-Herklotz index showed the lowest performance in the discrimination of alpha thalassemia and iron deficiency.

Haemoglobin Constant Spring (HbA2: c.427T>C) and Haemoglobin Adana (HbA2: c.179G>A) in jaundiced Malaysian term neonates with clinically significant hyperbilirubinemia.

INTRODUCTION: Haemoglobin Constant Spring (Hb CoSp) and Haemoglobin Adana (Hb Adana), are two non-deletion type of α-thalassemia reported in Malaysia. Owing to their structural instability, they cause hemolysis and hyperbilirubinemia. This observational study was part of a large study investigating multiple factors associated with severe neonatal jaundice. In this part we aimed to determine the prevalence of Hb CoSp and Hb Adana and their association with clinically significant neonatal hyperbilirubinemia (SigNH, total serum bilirubin (TSB>290µmol/L)) among jaundiced Malaysian term neonates. MATERIALS AND METHODS: The inclusion criteria were normal term-gestation neonates admitted consecutively for phototherapy. PCR-restriction fragment length polymorphism method was applied on DNA extracted from dry blood spot specimens of each neonate to detect for Hb CoSp and Hb Adana gene. Positive samples were verified by gene sequencing. RESULTS: Of the 1121 neonates recruited (719 SigNH and 402 no-SigNH), heterozygous Hb CoSp gene was detected in only two (0.27%) neonates. Both were SigNH neonates (0.3% or 2/719). No neonate had Hb Adana variant. CONCLUSION: Hb CoSp was not common but could be a risk factor associated with SigNH. No Hb Adana was detected.

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers.

BACKGROUND: The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV-exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. METHODS: A 3-year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high-burden districts, (2) document the prevalence among HIV-exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co-inheritance of known genetic modifiers of sickle cell disease. RESULTS: A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid-Northern districts, in both HIV-exposed and nonexposed children. Based on crude birth-rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40-0.64, P < .0001). Alpha-thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution. CONCLUSIONS: High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district-level comprehensive care programs.

Presentation of Compound Heterozygous Hemoglobin Constant Spring and Hemoglobin Pakse in Neonates.

BACKGROUND: Mutations causing α thalassemia are divided into deletion and nondeletion groups. In the nondeletion group, hemoglobin constant spring (Hb CS) and hemoglobin Pakse (Hb Pakse) are both caused by a termination codon mutation leading to elongation of the α2 globin gene. In the case of Hb CS, the mutation is TAA→CAA, whereas the mutation causing Hb Pakse is TAA→TAT. Clinical hematologic phenotypes are not significantly different. It is important to identify compound heterozygotes for purposes of genetic counseling. METHODS: We report 5 neonates with compound heterozygous Hb CS/Hb Pakse mutations with respect to clinical courses, hematologic profiles, and management. RESULTS: Among 5 cases (3 male babies and 2 female babies) with mean birth weight 2982 g (range, 2660 to 3440 g), 3 were diagnosed as compound heterozygous Hb CS/Hb Pakse, 1 as homozygous Hb E with compound heterozygous Hb CS/Hb Pakse, and 1 as heterozygous Hb E with compound heterozygous Hb CS/Hb Pakse. Clinical manifestations included fetal anemia (1 case), neonatal hyperbilirubinemia (5), neonatal anemia (2), hepatosplenomegaly (1), and cholestatic jaundice (1). Three cases required a single phototherapy; 2 cases needed double phototherapy for treatment of severe hyperbilirubinemia. During the first few months of life, all cases had mild anemia, slightly low mean corpuscular volume, wide red cell distribution width, and low red cell counts. At 1 to 3 years of age, all patients still had mild microcytic hypochromic anemia with Hb levels around 10 g/dL, increased reticulocyte count, and wide red cell distribution width. CONCLUSIONS: Misdiagnosis of Hb Pakse could occur via Hb typing using Hb electrophoresis, because the band comigrates with that of Hb CS. DNA study is the definitive method for diagnosis.

Clinical Features and Genotypes of Patients with Hemoglobin H Disease in Taiwan.

BACKGROUND: The genetic background of patients with hemoglobin (Hb) H disease in Taiwan has been investigated; however, the clinical features and treatment outcomes were not reported. OBJECTIVE: To analyze the clinical features and genotypes of patients with HbH who reside in Taiwan. METHODS: We conducted a retrospective analysis of the clinical and molecular characteristics of 38 patients with HbH disease who were undergoing treatment at Kaohsiung Medical University Hospital, Taiwan. RESULTS: Initial Hb levels were lower and the numbers of patients requiring iron-chelation therapy were higher in the nondeletional HbH group than in the deletional HbH group (P <.05). Compared with the healthy population, the patients with HbH disease exhibited short body length, low body weight, and low body mass index (BMI). CONCLUSIONS: Patients with nondeletional HbH disease had lower Hb levels and a higher requirement for splenectomy and iron-chelation therapy than did those with deletional HbH disease. Also, growth status was compromised in patients with HbH disease.

Anaemia among females in child-bearing age: Relative contributions, effects and interactions of α- and ß-thalassaemia.

INTRODUCTION: Anaemia in women during pregnancy and child bearing age is one of the most common global health problems. Reasons are numerous, but in many cases only minimal attempts are made to elucidate the underlying causes. In this study we aim to identify aetiology of anaemia in women of child bearing age and to determine the relative contributions, effects and interactions of α- and ß-thalassaemia in a region of the world where thalassaemia is endemic. METHODS: A cross sectional study was conducted at the Colombo North Teaching Hospital of Sri Lanka. The patient database of deliveries between January 2015 and September 2016 at University Obstetrics Unit was screened to identify women with anaemia during pregnancy and 253 anaemic females were randomly re-called for the study. Data were collected using an interviewer-administered questionnaire and haematological investigations were done to identify aetiologies. RESULTS: Out of the 253 females who were anaemic during pregnancy and were re-called, 8 were excluded due to being currently pregnant. Of the remaining 245 females, 117(47.8%) remained anaemic and another 22(9.0%) had non-anaemic microcytosis. Of anaemic females, 28(24.8%) were iron deficient, 40(35.4%) had low-normal serum ferritin without fulfilling the criteria for iron deficiency,18(15.3%) had ß-haemoglobinopathy trait and 20(17.0%) had α-thalassaemia trait. Of females who had non-anaemic microcytosis, 14(66.0%) had α-thalassaemia trait. In 4 females, both α- and ß-thalassaemia trait coexist. These females had higher levels of haemoglobin (p = 0.06), MCV (p<0.05) and MCH (p<0.01) compared to individuals with only ß-thalassaemia trait. A significantly higher proportion of premature births (p<0.01) and lower mean birth weights (p<0.05) were observed in patients with α-thalassaemia trait. CONCLUSIONS: Nearly one third of anaemic females in child bearing age had thalassaemia trait of which α-thalassemia contributes to a majority. Both α- and ß-thalassaemia trait can co-exist and have ameliorating effects on red cell indices in heterozygous states. α-Thalassaemia trait was significantly associated with premature births and low birth weight. It is of paramount importance to investigate the causes of anaemia in women of child bearing age and during pregnancy in addition to providing universal iron supplementation.

Haemoglobin variants, iron status and anaemia in Sri Lankan adolescents with low red cell indices: A cross sectional survey.

Iron deficiency complicates the use of red cell indices to screen for carriers of haemoglobin variants in many populations. In a cross sectional survey of 7526 secondary school students from 25 districts of Sri Lanka, 1963 (26.0%) students had low red cell indices. Iron deficiency, identified by low serum ferritin, was the major identifiable cause occurring in 550/1806 (30.5%) students. Low red cell indices occurred in iron-replete students with alpha-thalassaemia including those with single alpha-globin gene deletions. Anaemia and low red cell indices were also common in beta-thalassaemia trait. An unexpected finding was that low red cell indices occurred in 713 iron-replete students with a normal haemoglobin genotype. It is common practice to prescribe iron supplements to individuals with low red cell indices. Since low red cell indices were a feature of all forms of α thalassaemia and also of iron deficiency, in areas where both conditions are common, such as Sri Lanka, it is imperative to differentiate between the two, to allow targeted administration of iron supplements and avoid the possible deleterious effects of increased iron availability in iron replete individuals with low red cell indices due to other causes such as α thalassaemia.

Malaria and Age Variably but Critically Control Hepcidin Throughout Childhood in Kenya.

Both iron deficiency (ID) and malaria are common among African children. Studies show that the iron-regulatory hormone hepcidin is induced by malaria, but few studies have investigated this relationship longitudinally. We measured hepcidin concentrations, markers of iron status, and antibodies to malaria antigens during two cross-sectional surveys within a cohort of 324 Kenyan children ≤ 8 years old who were under intensive surveillance for malaria and other febrile illnesses. Hepcidin concentrations were the highest in the youngest, and female infants, declined rapidly in infancy and more gradually thereafter. Asymptomatic malaria and malaria antibody titres were positively associated with hepcidin concentrations. Recent episodes of febrile malaria were associated with high hepcidin concentrations that fell over time. Hepcidin concentrations were not associated with the subsequent risk of either malaria or other febrile illnesses. Given that iron absorption is impaired by hepcidin, our data suggest that asymptomatic and febrile malaria contribute to the high burden of ID seen in African children. Further, the effectiveness of iron supplementation may be sub-optimal in the presence of asymptomatic malaria. Thus, strategies to prevent and eliminate malaria may have the added benefit of addressing an important cause of ID for African children.

[Application of multiplex ligation-dependent probe amplification technique in prenatal diagnosis of α-thalassemia].

OBJECTIVE To assess the application value of multiplex ligation-dependent probe amplification (MLPA) for the detection of gene deletion and prenatal diagnosis of α-thalassemia. METHODS MLPA was applied for 2 cases with α-thalassemia phenotype by whole blood cell counting and hemoglobin component detection but were ruled out by regular molecular diagnosis. Potential gene deletions and point mutations of α-thalassemia gene were detected with regular Gap-polymerase chain reaction (Gap-PCR) and reverse dot blotting (RDB) in 89 cases where one or both partners were carriers of α-thalassemia mutations. Meanwhile, MLPA was used for detecting α-globin gene deletion among the 89 samples. RESULTS For the 2 cases with α-thalassemia phenotype, no α globin gene deletion was detected by MLPA, but were subsequently confirmed as iron-deficiency anemia. The results of MLPA and Gap-PCR detection for the 88 cases were consistent, except for 1 fetal sample (chorionic villi) which could not be diagnosed by Gap-PCR and was confirmed to be - SEA/αα by MLPA. CONCLUSION MLPA can be applied to prenatal diagnosis of α-thalassemia as an effective supplement to Gap-PCR to reduce both misdiagnosis and missed diagnosis and improve the accuracy of prenatal diagnosis.

Discrimination of various thalassemia syndromes and iron deficiency and utilization of reticulocyte measurements in monitoring response to iron therapy.

Decreased hemoglobinization of red cells resulting in hypochromia and microcytosis are the main features of thalassemia syndromes, and also of iron deficiency anemia (IDA). A simple and reliable method is required to distinguish the two conditions in the routine laboratories. In this study we analyzed the red cell and reticulocyte parameters from 414 samples of various types of thalassemias and IDA and discovered a variety of discriminating criteria including a discrimination index (DI) which should be useful for differential diagnosis. Slightly decreased MCV and CH are suggestive of α-thalassemia 2, Hb CS, and Hb E heterozygotes whereas the increased Rbc counts are obvious in α-thalassemia 1 and ß-thalassemia. In Hb E, the number of microcytic red cells was greater than the number of hypochromic red cells resulting in an increased M/H ratio. Hb H diseases are characterized by a higher number of hypochromic red cells and decreased CHCM, while broadening of hemoglobin concentration histogram results in increased HDW in ß-thalassemia diseases. Iron deficiency anemia results in hypochromic-microcytic red cells and increased RDW. The number of reticulocyte with %High Retic and CHr value were increased in the first month of iron supplementation indicating the response to iron therapy.

Sickle cell disease in children: chronic complications and search of predictive factors for adverse outcomes.

BACKGROUND: Sickle cell disease (SCD) has extremely variable phenotypes, and several factors have been associated with the severity of the disease. OBJECTIVES: To analyze the chronic complications of SCD and look for predictive risk factors for increased severity and number of complications. METHODS: Retrospective study including all children followed for SCD in the Paediatric Haematology Unit of a tertiary hospital in Portugal, who completed 17 yr old between the years 2004 and 2013. RESULTS: We identified 44 patients, 55% female and 98% black. Chronic complications occurred in 80% of cases. Slight dilatation of the left ventricle was the most frequent complication (47.7%), followed by respiratory function disturbs (43.2%), microlithiasis or cholelithiasis (40.9%), increased flow velocity of cerebral arteries (31.8%), enuresis, delayed puberty and bone abnormalities (6.8% each), sickle cell retinopathy and leg ulcer (4.6% each) and recurrent priapism (2.3%). We identified a statistically significant association between leukocytes >15 000/µL and a higher number of hospitalizations (P < 0.001) and chronic complications of the disease (P = 0.035). The occurrence of dactylitis in first year of life was also significantly associated with a higher number of hospitalizations (P = 0.004) and chronic complications (P = 0.018). The presence of α-thalassemia was associated with a lower number of chronic complications (P = 0.036). CONCLUSIONS: Leucocytosis and dactylitis in the first year of life can be predictors of SCD severity, while the presence of α-thalassemia can be protective. The determination of early predictors of chronic complications of SCD may improve the comprehensive care of these patients.

Application of multiplex ligation-dependent probe amplification technique in prenatal diagnosis of α-thalassemia / 中华医学遗传学杂志

OBJECTIVE To assess the application value of multiplex ligation-dependent probe amplification (MLPA) for the detection of gene deletion and prenatal diagnosis of α-thalassemia. METHODS MLPA was applied for 2 cases with α-thalassemia phenotype by whole blood cell counting and hemoglobin component detection but were ruled out by regular molecular diagnosis. Potential gene deletions and point mutations of α-thalassemia gene were detected with regular Gap-polymerase chain reaction (Gap-PCR) and reverse dot blotting (RDB) in 89 cases where one or both partners were carriers of α-thalassemia mutations. Meanwhile, MLPA was used for detecting α-globin gene deletion among the 89 samples. RESULTS For the 2 cases with α-thalassemia phenotype, no α globin gene deletion was detected by MLPA, but were subsequently confirmed as iron-deficiency anemia. The results of MLPA and Gap-PCR detection for the 88 cases were consistent, except for 1 fetal sample (chorionic villi) which could not be diagnosed by Gap-PCR and was confirmed to be - SEA/αα by MLPA. CONCLUSION MLPA can be applied to prenatal diagnosis of α-thalassemia as an effective supplement to Gap-PCR to reduce both misdiagnosis and missed diagnosis and improve the accuracy of prenatal diagnosis.

[Current management of thalassemia intermedia]. / Prise en charge actuelle des thalassémies intermédiaires.

Thalassemia intermedia is a clinical entity where anemia is mild or moderate, requiring no or occasional transfusion. Non-transfusion-dependent thalassemia encompasses 3 main clinical forms: beta-thalassemia intermedia, hemoglobin E/beta-thalassemia and alpha-thalassemia intermedia (HbH disease). Clinical severity of thalassemia intermedia increases with age, with more severe anemia and more frequent complications such as extramedullary hematopoiesis and iron overload mainly related to increased intestinal absorption. Numerous adverse events including pulmonary hypertension and hypercoagulability have been associated with splenectomy, often performed in thalassemia intermedia patients. The potential preventive benefit of transfusion and chelation therapies on the occurrence of numerous complications supports the strategy of an earlier therapeutic intervention. Increasing knowledge about pathophysiological mechanisms involved in thalassemia erythropoiesis and related iron overload is currently translating in novel therapeutic approaches.

Alpha thalassaemia in tribal communities of coastal Maharashtra, India.

BACKGROUND & OBJECTIVES: In a routine community health survey conducted in adult Adivasis of the costal Maharashtra, microcytosis and hyprochromia were observed in more than 80 per cent of both males and females having normal haemoglobin levels suggesting the possibility of α-thalassaemia in these communities. We conducted a study in Adivasi students in the same region to find out the magnitude of α-thalessaemia. METHODS: The participants (28 girls and 23 boys) were 14-17 yr old studying in a tribal school. Fasting venous blood samples (5 ml) were subjected to complete blood count (CBC), Hb-HPLC and DNA analysis using gap-PCR for deletion of -α3.7 and -α4.2, the two most common molecular lesions observed in α-thalassaemia in India. RESULTS: Microcytic hypochromic anaemia was observed 50 and 35 per cent girls and boys, respectively. Iron supplementation improved Hb levels but did not correct microcytois and hypochromia. m0 ore than 80 per cent non-anaemic students of both sexes showed microcytois and hypochromia. DNA analysis confirmed that the haematological alterations were due to α-thalassaemia trait characterized by deletion of -α3.7. Majority (>60%) of the affected students had two deletions (-α3.7/-α3.7 genotype α+ thalassaemia. INTERPRETATION & CONCLUSIONS: This is perhaps the first report on the occurrence of α-thalassaemia in tribal communities of coastal Maharashtra. Very high (78.4%) haplotype frequency of -α3.7 suggests that the condition is almost genetically fixed. These preliminary observations should stimulate well planned large scale epidemiological studies on α-thalassaemia in the region.

Successful unrelated cord blood transplantation for homozygous α-thalassemia.

A now 10-year-old Laotian female was delivered at 30-week gestation by cesarean section because of severe hydrops. Fetal blood sampling revealed homozygous α-thalassemia. After immediate resuscitation, the infant was supported with frequent red cell transfusions. At 44 months of age, she received a 5 of 6 human leukocyte antigen-matched unrelated cord blood transplantation. She was treated with phlebotomy and chelation therapy with Deferasirox for correction of hemosiderosis and has been transfusion-independent since 41 days after transplant. She is currently 6 years after transplantation with stable, 100% donor engraftment, resolved iron overload, and normal growth and development.