Homozygous Α-thalassemia Research Articles

Diagnosis of α-thalassaemia by colorimetric gap loop mediated isothermal amplification

α-Thalassaemia is an inherited haemoglobin disorder that results from the defective synthesis of α-globin protein. Couples whom both carry the α-thalassaemia 1 gene are at risk of having a foetus with the most severe thalassaemia, Hb Bart’s hydrops fetalis, with a risk of maternal mortality. However, haematological parameters alone cannot distinguish between a α-thalassaemia 1 carrier and a homozygous α-thalassaemia 2, in which one α-globin gene has been deleted on each chromosome. A rapid and accurate molecular detection assay is essential for prevention of the disease in populations where α-thalassaemia 1 is common. Multiplex Gap-PCR analysis is widely used for diagnosis of α-thalassaemia. However, the technique requires a thermocycler and post-amplification processing, which limits its application in primary care or in rural areas in developing countries. Loop mediated isothermal amplification (LAMP) amplifies target DNA at a constant temperature and does not require a thermocycler. This study developed a colorimetric Gap-LAMP using malachite green to allow naked eye visualization of two deletional α-thalassaemia 1 commonly found in Asian populations, the Southeast Asian type (--SEA) and the Thai type (--THAI) deletions. The Gap-LAMP was performed on DNA samples from 410 individuals carrying various α-thalassaemia gene defects with 100% concordance with conventional Gap-PCR analysis. This method eliminates post-amplification processing or the use of expensive sophisticated equipment and allows screening large populations for the prevention and control of α-thalassaemia.

Impact of haemoglobinopathies on asymptomatic Plasmodium falciparum infection and naturally acquired immunity among children in Northern Ghana

BackgroundThe protective effect of certain haemoglobinopathies, such as HbS, HbC, and α-thalassaemia, against severe malaria has long been established; however, there is only limited and equivocal evidence regarding their impact on asymptomatic parasitaemia. Here, we investigated the effect of HbS, HbC, and α-thalassaemia on asymptomatic P. falciparum parasitaemia and acquired immunity among children in Northern Ghana.Materials and methodsA cross-sectional study was conducted among 1,017 healthy children (1-17 years) in 13 malaria-endemic communities in Northern Ghana. The children were screened for structural Hb phenotypes using SickleSCAN, for P. falciparum infection using anti-HRP2 malaria RDT and subsequently confirmed by capillary electrophoresis and PCR, respectively. α-thalassaemia genotyping was done using PCR. Levels of IgG specific for six recombinant malaria antigens (PfCSP, GLURP, MSP3, Pfs230, HB3VAR06, and IT4VAR60) and crude asexual blood-stage antigens were evaluated by ELISA.Results266 out of the 1,017 participants had either HbAC (18%) or HbAS (8.4%), whereas 35% had α‐thalassaemia. Twenty-five percent and 6% HbAC individuals co-inherited heterozygous and homozygous α-thalassaemia respectively. Similarly, 25% and 10.5% of HbAS co-inherited heterozygous and homozygous α-thalassaemia. Asymptomatic parasitaemia rates were 23%, 24%, and 19% in those with HbAA, HbAC and HbAS, respectively. The overall parasite carriage rates in heterozygous (21%) and homozygous α-thalassaemia (25%) individuals were similar to that of individuals without α-thalassaemia (23%). P. falciparum parasite carriage risk was about three times higher among homozygous α-thalassaemia individuals with HbAC (OR = 2.97; 95% CI 0.83-10.62) and heterozygous carriers with HbAS variants (OR = 2.86; 95% CI 0.85-9.60) compared to the wildtype. In HbAS individuals, IgG levels to IT4VAR60 and HB3VAR06 were significantly lower, whereas anti-CSP levels were higher than in HbAA and HbAC.ConclusionsCo-inheritance of HbAS and HbAC with α-thalassaemia increased the risk of asymptomatic parasitaemia, an indication of a negative epistatic effect between these Hb variants. Antibody levels against non-PfEMP1 antigens were slightly higher among HbAS children, but quite similar in all study groups, indicating differences in parasite exposure.

Comparisons of oxygen gradient ektacytometry parameters between sickle cell patients with or without α‐thalassaemia

The present study tested the impact of α-thalassaemia on oxygen gradient ektacytometry in sickle cell anaemia (SCA). Three SCA groups were compared: (i) no α-thalassaemia (four α-genes, n = 62), (ii) silent α-thalassaemia (three α-genes, n = 35) and (iii) homozygous α-thalassaemia (two α-genes, n = 12). Red blood cell (RBC) deformability measured in normoxia was not different between the three groups. The lowest RBC deformability reached at low oxygen partial pressure (pO2 ) was greater and the pO2 at which RBC started to sickle was lower in the two α-genes group compared to the other groups. Our present study showed an effect of α-thalassaemia on oxygen gradient ektacytometry in SCA.

Epidemiology of thalassemia among the hill tribe population in Thailand.

Thalassemia is a severe disease that occurs due to abnormalities in hemoglobin genes. Various genetic factors in different populations lead to different clinical manifestations of thalassemia disease, particularly among people who have a long history of migration and who have married among tribes, such as the hill tribe people in Thailand. This genetic epidemiological study aimed to estimate the prevalence of various forms of thalassemia among the six main hill tribe populations in Thailand. A cross-sectional study was conducted to obtain information and blood specimens from school children belonging to one of the six main hill tribes in Thailand: Akha, Lau, Hmong, Yao, Karen, and Lisu. Hill tribe children who were attending grades 4-6 in 13 selected schools in Chiang Rai Province, Thailand, were invited to participate in the study. A validated questionnaire and 3 mL blood specimens were collected after obtaining information consent forms from both the children and their parents on a voluntary basis. A complete blood count (CBC) was performed, followed by osmotic fragility (OF) and dichlorophenol indophenol precipitation (DCIP) tests to screen for thalassemia. High-performance liquid chromatography (HPLC) and real-time quantitative polymerase chain reaction (qPCR) were used to identify hemoglobin type and α-thalassemia, respectively. A t-test, chi-square and logistic regression were used to detect the associations between variables at the significance level of α = 0.05. A total of 1,200 participants from 6 different tribes were recruited for the study; 50.0% were males, and 67.3% were aged 11-12 years. The overall prevalence of thalassemia carriers according to the screening tests was 9.8% (117 of 1,200). Among the cases, 83 were A2A (59 cases were α-thalassemia 1 carrier or α-thalassemia 2 carrier or homozygous α-thalassemia 2, and 24 cases were β-thalassemia trait with or without α-thalassemia); 1 case was EE (homozygous Hb E with or without α-thalassemia); 31 cases were EA (30 cases were the Hb E trait, and 1 case was Hb E trait with or without α-thalassemia); 1 case was A2A Bart's H (Hb H disease α-thalassemia 1/α-thalassemia 2); and 1 case was A2A with abnormal Hb. The prevalence of the α-thalassemia 1 trait among the hill tribe population was 2.5%. The greatest prevalence of the α-thalassemia 1 trait was found in the Karen (3.0%) and Hmong (3.0%) tribes. The prevalence of some forms of thalassemia in the hill tribe population is higher than that in the Thai and other populations. Effective and available thalassemia screening tests, including essential information to protect the next generation through the specific counseling clinic, are crucial, particularly due to increasing marriages within these populations.

Influence of hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency on diagnosis of diabetes by HbA1c among Tanzanian adults with and without HIV: A cross-sectional study.

IntroductionHemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders.MethodsBlood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT).ResultsThe mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM.ConclusionsHbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.

Perinatal Management of Bart's Hemoglobinopathy: Paradoxical Effects of Intrauterine, Transplacental, and Partial Exchange Transfusions

We describe a fetus at 24 3/7 weeks' gestation that showed ultrasound evidence of anemia, hydrops, and severe growth restriction. Both parents were known to be cis heterozygous carriers for SEA α-thalassemia deletion (αα/–). Cordocentesis confirmed fetal anemia and homozygous α-thalassemia (−/−) in the fetus. Fetal intrauterine transfusions corrected the anemia, treated the hydrops, and improved fetal growth. The postnatal course was complicated by hypoxic respiratory failure and persistent pulmonary hypertension of the newborn, which resolved only after partial volume exchange transfusion. This case report is presented to point out the potential unintended outcomes with transplacental transfusion via delayed cord clamping and cord milking at delivery in the setting of congenital Bart's hemoglobinopathy, and demonstrates that partial exchange transfusion of the newborn may optimize oxygen delivery due to the more favorable oxygen affinity of transfused adult hemoglobin compared with the Bart's hemoglobin.

Re-Assessing the Red Blood Cell Lifespan in Sickle Cell Anemia: Does Size Matter?

Background: Does the size of RBCs in sickle cell anemia (SCA) influence their lifespan? According to Ballas and Marcolina's study of 26 SCA patients (Hemoglobin 2000), the half-life of 51Cr labelled RBCs (T1/2) had a statistically significant negative correlation with MCV (p = 0.009), that was described by the regression equation: T1/2 (days) = 9.3 - 0.22 x [MCV (fL) - 87]. We have used this equation to derive a quantitative relationship between the RBC lifespan (LSRBC) and RBC size (MCV) and have tested this relationship with the data of Higgs et al. (N Engl J Med 1982) in SCA patients with and without concomitant α-thalassemia. We also reassessed the RBC survival kinetics of non-F-cells in 12 SCA patients (Franco et al. Blood 2006) to explore a size effect. A mechanistic hypothesis for a causal relationship between RBC size and LSRBC is proposed.Methods: The numerical relationship between LSRBC and T1/2 was derived using Engstedt's theoretical model (Acta Med Scand. Suppl. 1957) for the case of auto-transfusion in patients with hemolytic anemia. Combining this relationship with the experimental regression equation of T1/2 vs. MCV yielded a prediction of the dependence of LSRBC vs. MCV, which was accurately represented by a 2nd degree polynomial. This dependence was used to estimate the LSRBC values corresponding to the 3 groups of SCA patients studied by Higgs et al. (N Engl J Med 1982), whose mean MCV values were 90.1 fL (4 α-globin genes), 84.4 fL (3 α-globin genes) and 71.2 fL (2 α-globin genes). For comparison, we estimated LSRBC values for patients with 4 and 2 α-globin genes directly from the T1/2 values reported by De Ceulaer et al. (N Engl J Med 1983). An indirect estimate of LSRBC was derived from the ratio of the reticulocyte lifespan to the % reticulocytes reported in the 3 groups, with the former parameter set to 1.82 days in order to match the LSRBC prediction of the 4 α-globin gene group. A further estimate was derived from the levels of total bilirubin, Hb and MCHC using a theoretical expression that was also adjusted to match the 4 α-globin gene prediction. From the data on RBC survival kinetics in SCA patients reported by Franco et al. (Blood 2006), we estimated the T50% survival times of non-F-cells and explored their relationship to MCV.Results: The dependence of LSRBC vs. MCV derived from Ballas and Marcolina's data (Hemoglobin 2000) shows a marked decrease from 25 days to 10 days as MCV increases from 73 to 101 fL (Figure 1). Using this relationship, a corresponding increase in the predicted LSRBC values is shown for the SCA patients of Higgs et al. (N Engl J Med 1982) with α-gene numbers corresponding to 4 (no α-thalassemia), 3 (heterozygous α-thalassemia) and 2 (homozygous α-thalassemia), respectively (Figure 2). The estimated LSRBC values derived from the data of De Ceulaer et al. (N Engl J Med 1983) in patients with 4 and 2 α-globin genes are in good agreement with our predictions (Figure 2). Indirect estimates of LSRBC, based on the % reticulocytes and total bilirubin levels reported by of Higgs et al. and adjusted to match the 4 α-globin gene group, are also in good agreement with the predicted LSRBC values for the 3 and 2 α-globin gene groups (Figure 2). Lastly the T50% survival times for non-F-cells derived from Franco et al. (Blood 2006) are seen to be inversely related to the MCV with a variation of about 3-fold (Figure 3).Discussion: Our reassessment of literature data in SCA patients illustrates a strong inverse relationship between the RBC lifespan and RBC size (MCV). The confounding of this finding by the presence of hetero- and homozygous α-thalassemia in the lower MCV groups cannot be excluded, nor can the influence of the MCHC, which varies weakly with MCV. Nonetheless, we suggest that this relationship could result from the following causal mechanism. Smaller RBCs (initially in the oxygenated state) should have a shorter capillary transit time than larger RBCs, as seen in theoretical simulations (Secomb and Hsu, Biophysical journal. 1996) and experimental studies (Du et al. PNAS 2015). A shorter transit time should limit the time for deoxygenation and HbS polymerization; leading to less sickling, less cell damage and less hemolysis. The reduced rate of hemolysis should result in a longer RBC lifespan. Our quantitative analysis and causal hypothesis suggest that size matters in the lifespan of sickle cells. The clinical and therapeutic implications of this hypothesis require further consideration. DisclosuresMazer:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Tomka:Roche: Employment. Winter:Roche: Employment. Koerner:F. Hoffmann-La Roche Ltd: Employment.

Generation of iPSC line MU011.A-hiPS from homozygous α-thalassemia fetal skin fibroblasts

Human iPSC line MU011.A-hiPS was generated from homozygous α-thalassemia (−SEA/−SEA) fetal skin fibroblasts using a non-integrative reprogramming method. Reprogramming factors OCT3/4, SOX2, KLF4, L-MYC, LIN28, and shRNA of TP53 contained in three episomal vectors were delivered using electroporation.

First-trimester combined screening for trisomy 21 in women at risk for α-thalassemia

Objective: To report the strategy of first-trimester aneuploidy screening in pregnancies at risk for homozygous α0-thalassemian.Methods: Women at risk of homozygous α0-thalassemia were given an ultrasound examination at 11–14 weeks’ gestation to exclude an affected pregnancy. Fetal cardiothoracic ratio (CTR) and nuchal translucence (NT) were measured. If cardiomegaly was found, chorionic villus sampling (CVS) was offered for α-thalassemia; otherwise the first-trimester combined screening test was performed on the pregnancy. The invasive testing for karyotyping was only followed in those cases with a positive aneuploidy screening test.Results: In total, 69 of 288 pregnancies were found to be affected by homozygous α0-thalassemia using ultrasound, and the findings were confirmed by invasive testing. In the remaining 219 pregnancies, invasive testing was not performed for α-thalassemia because of a normal fetal CTR, and the women received the first-trimester combined screening. Nine CVS procedures were performed for karyotyping because of a positive aneuploidy screening. Totally three pregnancies with aneuploidy were diagnosed and terminated.Conclusions: Our strategy can selectively detect aneuploidy pregnancies not affected by homozygous α-thalassemia, and, meanwhile, save on the cost of unnecessary aneuploidy screening or karyotyping in pregnancies with an affected fetus of homozygous α0-thalassemia.

Transfusion Dependent Homozygous α-Thalassemia in Patients Associated with Hypospadias in Three Survivors

Alpha-thalassemia results from a dysfunction of the α-globin gene. Types of mutations include large deletions and point mutations. The most severe form of α-thalassemia is hydrops fetalis, which is caused by homozygosity of certain types of either deletion or point mutations, and some cases were the results of a combination of both. Here, we describe three cases of homozygous α-thalassemia who continue to survive, all with hypospadias. The first two cases were 5-year-old twins that were diagnosed with homozygous SEA deletion and the first description of a 20- month-old child with the genotype of the homozygous Cd 59 (GGC>GAC) mutation of the HBA2 gene. Prognoses for any α-thalassemia mutation types that are known to lead to hydrops fetalis in male fetuses should be informed about the potential survival associated with hypospadias.

Chorionic villus sampling for early prenatal diagnosis: Experience at a mainland Chinese hospital

The aim of this study was to describe the experience of transabdominal chorionic villus sampling (CVS) at a mainland Chinese hospital. During a 7-year period, 1,172 pregnant women chose to have CVS for prenatal diagnosis. Details and outcome of all of these cases were reviewed. The median maternal age was 29 years (range 19–45). The median gestational age was 12 weeks (range 10–14). Fetal karyotyping and thalassaemia couples were the main indications (97.2%). Overall, 112 (9.7%) chromosomal abnormalities were identified. There were 91 (7.8%) major chromosomal abnormalities, including autosomal trisomy in 70 patients, sex chromosomal abnormalities in 17, triploidy in two and unbalanced chromosomal rearrangement abnormality in two. Additionally, 137 fetuses with severe thalassaemia syndrome were found, including 86 homozygous β-thalassaemia, and 51 homozygous α-thalassaemia or non-deletional haemoglobin H disease. The procedure failed to obtain an adequate sample in four (0.3%) patients. There were 229 pregnancies terminated for medical indications after CVS. There were three (0.3%) potentially procedure-related fetal losses. CVS is a safe and reliable prenatal diagnostic technique. It should be one of the options available to pregnant women who require prenatal diagnosis.

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.

A Case of Nonimmune Hydrops Fetalis Caused by Homozygous α-Thalassemia

Hydrops fetalis is a serious condition which indicates poor prognosis for the affected fetus. Although the incidence of isoimmune hydrops fetalis has decreased markedly, nonimmune hydrops fetalis cases have been more frequently reported. Nonimmune-mediated hydrops can be caused by hemoglobinopathies. In this report we present a case of nonimmune hydrops fetalis caused by homozygous α-thalassemia. Because of the high incidence of the disease in our country, α-thalassemia should be investigated in all cases with nonimmune hydrops fetalis. Conflict of interest:None declared.

Determinants of anemia among preschool children in rural, western Kenya.

Although anemia in preschool children is most often attributed to iron deficiency, other nutritional, infectious, and genetic contributors are rarely concurrently measured. In a population-based, cross-sectional survey of 858 children 6–35 months of age in western Kenya, we measured hemoglobin, malaria, inflammation, sickle cell, α-thalassemia, iron deficiency, vitamin A deficiency, anthropometry, and socio-demographic characteristics. Anemia (Hb < 11 g/dL) and severe anemia (Hb < 7 g/dL) prevalence ratios (PRs) for each exposure were determined using multivariable modeling. Anemia (71.8%) and severe anemia (8.4%) were common. Characteristics most strongly associated with anemia were malaria (PR: 1.7; 95% confidence interval [CI] = 1.5–1.9), iron deficiency (1.3; 1.2–1.4), and homozygous α-thalassemia (1.3; 1.1–1.4). Characteristics associated with severe anemia were malaria (10.2; 3.5–29.3), inflammation (6.7; 2.3–19.4), and stunting (1.6; 1.0–2.4). Overall 16.8% of anemia cases were associated with malaria, 8.3% with iron deficiency, and 6.1% with inflammation. Interventions should address malaria, iron deficiency, and non-malarial infections to decrease the burden of anemia in this population.

Haemoglobinopathies and the clinical epidemiology of malaria: a systematic review and meta-analysis

Haemoglobinopathies can reduce the risk of malaria syndromes. We aimed to quantify the relation between different haemoglobin mutations and malaria protection to strengthen the foundation for translational studies of malaria pathogenesis and immunity. We systematically searched the Medline and Embase databases for studies that estimated the risk of malaria in patients with and without haemoglobinopathies up to Sept 9, 2011, and identified additional studies from reference lists. We included studies that enrolled mainly children or pregnant women and had the following outcomes: Plasmodium falciparum severe malaria, uncomplicated malaria, asymptomatic parasitaemia, or pregnancy-associated malaria, and Plasmodium vivax malaria. Two reviewers identified studies independently, assessed quality of the studies, and extracted data. We produced odds ratios (ORs; 95% CIs) for case-control studies and incidence rate ratios (IRRs; 95% CIs) for prospective studies. We did the meta-analysis with a random-effects model when equivalent outcomes were reported in more than one study. Of 62 identified studies, 44 reported data for haemoglobin AS, 19 for haemoglobin AC and CC, and 18 for α-thalassaemia. Meta-analysis of case-control studies showed a decreased risk of severe P. falciparum malaria in individuals with haemoglobin AS (OR 0·09, 95% CI 0·06-0·12), haemoglobin CC (0·27, 0·11-0·63), haemoglobin AC (0·83, 0·67-0·96), homozygous α-thalassaemia (0·63, 0·48-0·83), and heterozygous α-thalassaemia (0·83, 0·74-0·92). In meta-analysis of prospective trials only haemoglobin AS was consistently associated with protection from uncomplicated malaria (IRR 0·69, 95% CI 0·61-0·79); no haemoglobinopathies led to consistent protection from asymptomatic parasitaemia. Few clinical studies have investigated β-thalassaemia, haemoglobin E, P. vivax malaria, or pregnancy-associated malaria. Haemoglobin AS, CC, and AC genotypes and homozygous and heterozygous α-thalassaemia provide significant protection from severe malaria syndromes, but these haemoglobinopathies differ substantially in the degree of protection provided and confer mild or no protection against uncomplicated malaria and asymptomatic parasitaemia. Through attenuation of severity of malaria, haemoglobinopathies could serve as a model for investigation of the mechanisms of malaria pathogenesis and immunity. US National Institute of Allergy and Infectious Diseases.

In Utero Diagnosis and Management of a Fetus With Homozygous α-Thalassemia in the Second Trimester

Alpha thalassemia with the absence of 4 α-globin genes leads to fetal hydrops and fetal death from anemia. Historically considered a lethal condition, optimal in utero management of homozygous α-thalassemia is unclear. A fetus of Filipino descent at 26 weeks gestation presented with ultrasound evidence of anemia. Cordocentesis confirmed anemia and homozygous α-thalassemia (--/--). Intrauterine transfusion corrected anemia but fetal growth restriction and oligohydramnios persisted. Intrauterine exchange transfusion improved hemoglobin parameters, fetal growth, and oligohydramnios. The late preterm infant was delivered with classic limb reduction defects. Hemoglobin Bart's is nonfunctional for oxygen transport, and intrauterine exchange transfusion may be effective first-line therapy and further investigation is warranted.

Homozygous Hb Stanleyville-II [alpha2 78(EF7) Asn&gt;Lys; HBA2:c.237C&gt;A, not C&gt;G] associated with genotype −α3.7/−α3.7 in two Brazilian families

Several hemoglobin variants have electrophoretic behavior similar to hemoglobin S, which may lead to false diagnosis for sickle-cell disorders in newborn screening programs. A homozygous hemoglobin with S mobility was detected in two unrelated babies in Brazil. Isoelectric focusing and high-performance liquid chromatography assays, gene sequencing, and restriction fragment length polymorphism with AfeI were used to characterize the hemoglobin. Hb Stanleyville-II and -α(3.7) /-α(3.7) type I deletion in the α-globin gene was diagnosed. Parents were heterozygous for both Hb Stanleyville-II and α-thalassemia. Hypochromia and microcytosis were probably due to the homozygous α-thalassemia. Stanleyville-II gene mutation is HBA2:c.237C>A, or C>G, and this information on the Globin Gene Server should be updated; AfeI test is a fast and accurate method to detect it; NBS programs should consider the possibility of Hb Stanleyville-II whenever IEF shows one band in the HbS position, and another one between S and C.

Hydrops Fetalis in the Stillborn: A Series from the Central Region of Thailand

The purpose of this study was to analyze the cause of hydrops fetalis (HF) among fetal deaths in the central region of Thailand. Autopsy reports diagnosed as HF from 1999 to 2008 at King Chulalongkorn Memorial Hospital were retrieved, and the pathologic findings, clinical information, fetal ultrasonographic studies, and laboratory investigations were reviewed. There were 78 stillborn autopsies during this 10-year period; the mean gestational age was 28 weeks. The causes of fetal hydrops were identified in 88.5%; no cases of immune hydrops were detected. Anemia was the predominant cause of HF (n = 33; 42.2%): related to homozygous α-thalassemia (n = 17; 21.8%), twin-twin transfusion syndrome (n = 8; 10.2%), hemoglobin H (n = 3; 3.8%), lung hemorrhage (n = 1; 1.3%), adrenal hemorrhage (n = 1; 1.3%), and 3 cases of unspecified etiology (3.8%). Other causes of high-output failure included mass lesions resulting in vascular shunting (n = 2; 2.6%) and 1 case each (1.3% each) of maternal diabetes mellitus, intestinal lymphangiectasia, and Beckwith-Wiedemann syndrome. Causes resulting in low-output cardiac failure were congenital heart disease (n = 16; 20.5%) and thoracic space-occupying lesions (n = 7; 9%). The remaining causes included fetal infection (n = 5; 6.4%), congenital abnormalities suggestive of a chromosomal or genetic basis (n = 2; 2.6%), and 1 case (1.3%) of placental vascular thrombosis. Nine cases (11.5%) had no identifiable cause. Thus, the most common cause of HF in this series was homozygous α-thalassemia, reflecting the geographic location of this series.

HOMOZYGOUS α-THALASSEMIA WITH TRISOMY 7 MOSAICISM IN A LIVE-BORN INFANT

The authors report a male infant born at 35 weeks gestational age with an atypical presentation of homozygous α-thalassemia. The live-born infant displayed abnormalities of the upper limbs and genitalia, which are vascular-type disruptive defects associated with this disease. Cardiomegaly and placentomegaly were the only evidence of fetal hydrops. Postnatal karyotype revealed mosaicism for trisomy 7, yet another rare finding in a live-born. The authors discuss their institutional experience with each of these rare conditions and the potential contribution of each to the overall unusual clinical presentation in this patient. This is the first report of these simultaneous diagnoses.

Homozygous α-Thalassemia Treated with Intrauterine Transfusions and Unrelated Donor Hematopoietic Cell Transplantation

Recently, intrauterine transfusions and hematopoietic cell transplantation (HCT) have changed homozygous alpha-thalassemia from a frequently fatal disease to a potentially survivable condition. We present a patient with Hemoglobin Bart's disease who was cured after failing to engraft with 1 unrelated HCT, but engrafting after a second unrelated donor HCT.