Heterozygous Hemoglobinopathies Research Articles

Compound Heterozygous Hemoglobinopathy Complicated by Inaccurate Capillary Electrophoresis Zoning.

Compound Heterozygous Hemoglobinopathy Complicated by Inaccurate Capillary Electrophoresis Zoning.

Commentary on Compound Heterozygous Hemoglobinopathy Complicated by Inaccurate Capillary Electrophoresis Zoning.

Commentary on Compound Heterozygous Hemoglobinopathy Complicated by Inaccurate Capillary Electrophoresis Zoning.

Metalloprotein status in Indian patients with beta thalassemia trait

Introduction and Aim: Beta Thalassemia trait (BTT) is the most prevalent heterozygous hemoglobinopathy in Asian population. The current study aims to evaluate plasma antioxidant metalloproteins like SOD, ceruloplasmin, ferritin and correlate them with the trace elements in patients with BTT. Materials and Methods: The subjects included in the study were divided into two groups comprising of 40 BTT patients in group I and 40 age and sex matched normal individuals in group II. Cation exchange HPLC was used for hemoglobin variant analysis. Plasma iron, copper, ceruloplasmin and SOD were assayed using the spectrophotometric method while zinc was determined by atomic absorption spectrometry and ferritin by ECLIA. Results: There was a marked reduction in plasma trace elements in BTT compared to healthy controls. The decrease in zinc (p<0.001) and copper (p<0.04) was statistically significant. Both SOD and ferritin levels were significantly lower in BTT patients (p<0.001). However, an apparent decrease was observed in ceruloplasmin levels. Iron and ferritin showed a significant positive correlation (r=0.84 p=0.01), similarly copper and ceruloplasmin correlated positively (r=0.92 p=0.001) in BTT patients. Interestingly HbF correlated negatively with all the three trace elements. Conclusion: It can be concluded that decreased antioxidant metalloproteins may lead to free radical toxicity in BTT. The study highlights the indirect role of trace elements in oxidative stress and draws attention on the requirement for regular and timely assessment of metalloenzymes and periodic administration of trace elements in reduction of free radical damage and associated complications in BTT patients.

A Child With Jaundice

Question: An 11-year-old Haitian boy with a history of hemoglobin S/β thalassemia heterozygous hemoglobinopathy (HbS/β-Thal) presented with 3 days of fatigue, pruritis, jaundice, and hematochezia. He had no abdominal pain, fever, nausea, or vomiting and no appreciable tenderness or organomegaly on physical examination. He had no prior clinical manifestations or complications related to his HbS/β-Thal disease. Peripheral blood indices revealed a red blood cell count of 5.73 M/μL, a mean corpuscular volume of 62.7 fL, and a hematocrit of 35.9%.

Health services use by children identified as heterozygous hemoglobinopathy mutation carriers via newborn screening

BackgroundNewborn screening (NBS) for sickle cell disease incidentally identifies heterozygous carriers of hemoglobinopathy mutations. In Ontario, Canada, these carrier results are not routinely disclosed, presenting an opportunity to investigate the potential health implications of carrier status. We aimed to compare rates of health services use among children identified as carriers of hemoglobinopathy mutations and those who received negative NBS results.MethodsEligible children underwent NBS in Ontario from October 2006 to March 2010 and were identified as carriers or as screen-negative controls, matched to carriers 5:1 based on neighbourhood and timing of birth. We used health care administrative data to determine frequencies of inpatient hospitalizations, emergency department (ED) visits, and physician encounters through March 2012, using multivariable negative binomial regression to compare rates of service use in the two cohorts. We analyzed data from 4987 carriers and 24,935 controls.ResultsAdjusted incidence rate ratios (95% CI) for service use in carriers versus controls among children < 1 year of age were: 1.11 (1.06–1.17) for ED visits; 0.97 (0.89–1.06) for inpatient hospitalization; and 1.02 (1.00–1.04) for physician encounters. Among children ≥1 year of age, adjusted rate ratios were: 1.03 (0.98–1.07) for ED visits; 1.14 (1.03–1.25) for inpatient hospitalization and 0.92 (0.90–0.94) for physician encounters.ConclusionsWhile we identified statistically significant differences in health services use among carriers of hemoglobinopathy mutations relative to controls, effect sizes were small and directions of association inconsistent across age groups and health service types. Our findings are consistent with the assumption that carrier status is likely benign in early childhood.

Hemoglobinopathy in pediatric population: A cross sectional study at tertiary care center in Assam

Objectives: The objectives of the study were to find out the prevalence, epidemiology, and clinicohematological profile of hemoglobinopathies. Material and Methods: During the period of September 2010–August 2011, an observational study was done in the Department of Pediatrics, Assam Medical College and Hospital, Dibrugarh. Children (&lt;12 years) suffering from chronic anemia were the study population. Results: Hemoglobinopathies were noted in 72 (35.0%) out of 206 chronic anemia cases, of which sickle cell disease (SCD) was found in 23 cases (11.2%), beta-thalassemia major (BTM) in 21 cases (10.2%), hemoglobin E (HbE)-β thalassemia in 12 cases (5.8%), HbE disease was seen in 10 cases (4.8%), and HbE trait and sickle cell trait (SCT) in 3 cases each. Overall hemoglobinopathy was most commonly seen among teagarden community in Assam. Clinical presentation ranged from completely asymptomatic to congestive heart failure. In majority cases, decreased mean Hb (%) and mean corpuscular volume were found. Anisopoikilocytosis, reticulocytosis, and target cells were frequently noted in peripheral blood smear. Conclusion: Chronic anemia cases should be screened for hemoglobinopathies as these genetic disorders are commonly seen in Assam. SCD and BTM are the major types of hemoglobinopathies. Heterozygous hemoglobinopathies (HbE trait and SCT) had lesser clinical manifestations. As the definitive treatment of hemoglobinopathies is still difficult to avail in this region, genetic counseling should be considered for hemoglobinopathy patients and their families as well, to prevent new cases.

A1C Underperforms as a Diagnostic Test in Africans Even in the Absence of Nutritional Deficiencies, Anemia and Hemoglobinopathies: Insight From the Africans in America Study.

Introduction: To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living in America [male: 65% (281/441), age: 38 ± 10 y (mean ± SD), BMI: 27.5 ± 4.4 kg/m2] (1) nutritional and hematologic profiles and (2) glucose tolerance categorization by OGTT and A1C.Methods: Hematologic and nutritional status were assessed. Hemoglobin <11 g/dL occurred in 3% (11/441) of patients and led to exclusion. A1C and OGTT were performed in the remaining 430 participants. ADA thresholds for A1C and OGTT were used. Diagnosis by A1C required meeting either A1C-alone or A1C&OGTT criteria. Diagnosis by OGTT-alone required detection by OGTT and not A1C.Results: Hemoglobin, mean corpuscular volume and red blood cell distribution width were 14.0 ± 1.3 g/dL, 85.5 ± 5.3 fL, and 13.2 ± 1.2% respectively. B12, folate, and iron deficiency occurred in 1% (5/430), 0% (0/430), and 4% (12/310), respectively. Heterozygous hemoglobinopathy prevalence was 18% (78/430). Overall, diabetes prevalence was 7% (32/430). A1C detected diabetes in 32% (10/32) but OGTT-alone detected 68% (22/32). Overall prediabetes prevalence was 41% (178/430). A1C detected 57% (102/178) but OGTT-alone identified 43% (76/178). After excluding individuals with heterozygous hemoglobinopathies, the rate of missed diagnosis by A1C of abnormal glucose tolerance did not change (OR: 0.99, 95% CI: 0.61, 1.62).Conclusions: In nutritionally replete Africans without anemia or heterozygous hemoglobinopathy, if only A1C is used, ~60% with diabetes and ~40% with prediabetes would be undiagnosed.Clinical Trial Registration:: www.ClinicalTrials.gov, Identifier: NCT00001853

1494-P: Glycated Albumin May Be an Effective Alternative to A1C in the Presence of Hemoglobin C Trait

Hemoglobin C (HbC) trait is a heterozygous hemoglobinopathy common in West Africa. Due to interference with the HPLC assay, heterozygous hemoglobinopathies such as HbC trait may lead to readings for A1C which are artefactually low. Therefore, the value of A1C as a diagnostic test may be compromised. Glycated albumin (GA) may be an effective alternate to A1C because it is a nonfasting measure of glycemia which is not impacted by Hb variants. No study has focused on HbC trait and evaluated the ability of A1C and GA to detect glucose tolerance status. Our goals were to evaluate the diagnostic efficacy of A1C and GA in the detection of dysglycemia in the 4% (13/366) of African-born blacks enrolled in the Africans in America Study who had HbC trait documented by hemoglobin electrophoresis. OGTT was performed in the 13 participants (age 37±7y (mean±SD), BMI 26.9±3.4 kg/m2). Glucose tolerance status was defined by the OGTT. The ability of A1C≥5.7% and GA≥14.2% to diagnose dysglycemia was evaluated. Both A1C≥5.7% and GA≥14.2% represent the upper quartile cut-off for their distribution in the Africans in America cohort. Mean A1C was 4.8±0.7%, range 3.1- 5.6%. Mean GA was 13.9±1.3%, range 11.9 - 15.4%. Thirty-nine % (5/13) of the participants had prediabetes and 8% (1/13) had diabetes. However, A1C was &amp;lt;5.7% in all participants. Therefore, for A1C sensitivity and specificity were 0% and 100% resp. In contrast, for GA the sensitivity and specificity were 83% and 71%, resp. Although the number of individuals with HbC trait in our cohort was small, our findings suggest that GA may be an important screening test to be used in populations with a high prevalence of HbC trait. Disclosure S.M. Briker: None. M.F. Horlyck-Romanovsky: None. R. Mugeni: None. J.Y. Aduwo: None. C. DuBose: None. A.E. Sumner: None.

Abstract P115: Prevalence of Undiagnosed Diabetes Decreases by Eighty Percent When A1C Replaces the OGTT: The Africans in America Study

Introduction: Africa has the highest prevalence of undiagnosed diabetes (DM) in the world. It is unknown whether programs designed to screen for DM in Africa should rely on hemoglobin A 1C (A1C) or the 2h oral glucose tolerance test (OGTT). In general, the prevalence of undiagnosed DM is lower when detection is based on A1C rather than the OGTT. However, the degree to which the prevalence of undiagnosed DM would be lower in Africans if A1C rather than the OGTT was used is unknown. Heterozygous hemoglobinopathies such as sickle cell trait (SCT) and hemoglobin C (HbC) trait may lower A1C independent of the degree of glycemia, potentially compromising the ability of A1C to detect DM. Objective: Our goals were to determine in Africans the rate of detection and reproducibility of the diagnosis of DM by both A1C and OGTT. Methods: Ninety African-born blacks (66% (59/90) male, age 40±11y (mean±SD), BMI 27.6±4.6 kg/m 2 ) who self-identified as healthy, currently live in the Washington DC area and enrolled in the Africans in America study had two OGTT performed 10±8 days apart. At both visits A1C was assayed by HPLC from whole blood and glucose from plasma samples taken at -15, 0, 30, 60, 90 and 120 minutes. For A1C, DM was diagnosed by levels ≥6.5%. For the OGTT, fasting glucose ≥126 mg/dL or 2h glucose≥200 mg/dL was required to diagnose DM. The κ-statistic was used to evaluate reproducibility. Hemoglobin electrophoresis was performed. Results: At Visit 1: DM was diagnosed by A1C in 4% (4/90) and by OGTT in 26% (23/90). At Visit 2: DM was diagnosed by A1C in 3% (3/89) and by OGTT in 21% (19/90). Diagnosis by A1C and OGTT displayed substantial (κ=0.74) and almost perfect (κ=0.88) reproducibility, respectively. All persons with DM diagnosed by A1C criteria at either visit were also diagnosed by OGTT. However, 83% (19/23) of people with DM diagnosed by OGTT were not detected by A1C. In the entire cohort the combined prevalence of HbS and HbC trait was 14% (13/90). However, the prevalence of SCT and HbC trait in people with DM diagnosed by OGTT was 42% (8/19), but no one with SCT or HbC trait had an A1C level≥6.5%. Conclusion: Diagnosis of DM by both A1C and OGTT are highly reproducible in African immigrants. However, A1C detects 80% fewer people with DM than does the glucose criteria for the OGTT. The clinical consequences of this lower rate of detection of DM by A1C remains to be determined in prospective studies.

Kelainan pada Sintesis Hemoglobin: Thalassemia dan Epidemiologi Thalassemia

Hemoglobinopathy includes structural abnormalities and haemoglobin synthesis disorders (thalassemia), is a single gene disorder that was originally found in malaria endemic areas but nowadays can be found all over the world. The birth rate of homozygous or compound heterozygous hemoglobinopathies, including alpha and beta thalassemia is less than 2.4 per 1000 births. Sickle cell anemia is the most prevalent compared to beta major and HbE-beta thalassemia. In Southeast Asia with more than 600 million people, abnormalities in hemoglobin including thalassaemia, HbE and HbCS are the most common and highly prevalent genetic disorders. Indonesia, has several areas that are endemic to malaria, there are many cases of abnormalities in Hb including thalassemia. If the percentage of carriers is associated with the birth rate and the number of Indonesian population and based on the study, it is estimated that the number of thalassemia patients born each year around 2500 children. As the case of thalassemia is increasing from year to year, it is necessary that prevention starts with screening in individuals who have relatives known as a carrier or thalassemia patient.

A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy.

A comprehensive laboratory diagnosis of hemoglobinopathies forms an integral part in workup of disorders of globin chain synthesis. Clinical findings, complete blood counts, peripheral smear examination along with hemoglobin (Hb) electrophoresis and/or cation exchange high performance liquid chromatography findings and parental study helps to clinch a final diagnosis. Compound heterozygous hemoglobinopathy presents with variable clinical findings and some of them are picked up on screening tests done as part of routine antenatal workup. Here we report a rare double heterozygous hemoglobinopathy of Hb D-Punjab and Hb J-Meerut in a 35year antenatal female.

A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy

ObjectivesTo report the finding of a novel double heterozygous hemoglobinopathy, the coinheritance of Hb Fontainebleau (α-chain variant) with HbD-Punjab (β-chain variant) discovered upon investigation of unexplained microcytosis in an infant. Design and methodsHemoglobinopathy investigation was performed by high performance liquid chromatography (HPLC) using the β-thalassemia Short Program on the Bio-Rad Variant IITM followed by gel electrophoresis at alkaline and acid pH (Sebia Hydrasys 2 Electrophoresis System) and molecular diagnostic testing. This study complied with our institutional board ethics requirements. ResultsHPLC and electrophoresis suggested a complex α- and β-chain hemoglobinopathy with presumptive identification of the beta Hb variant as Hb D-Punjab. DNA sequencing analysis revealed the presence of a double heterozygous status for Hb Fontainebleau/Hb D-Punjab. ConclusionsIn this paper we report the coinheritance of Hb Fontainebleau with Hb D-Punjab.

Incidence of hemoglobinopathies and thalassemias in Northern Alberta. Establishment of reference intervals for HbF and HbA2

ObjectivesThe aims of this study were to identify the incidence of hemoglobinopathies and thalassemias in Northern Alberta and calculate the reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. MethodsA retrospective ad-hoc analysis of the structural Hb variants and thalassemias identified on patients who had a hemoglobinopathy/thalassemia investigation performed between February 1 to December 31, 2013. Results were extracted from the Laboratory Information System. Statistical analysis was performed using MedCalc® version 11.4.2.0 for Windows software. Results6616 hemoglobinopathy/thalassemia investigations and HbS screens were physician requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438 were interpreted as “normal” and 532 were classified as iron deficient. 3306 individuals, with age ranging from 3 to 92years were included in the RI calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 α and β thalassemia traits respectively were identified. Additionally ten δβ thalassemia traits and twelve cases of HbH disease were identified. Regarding hemoglobinopathies, 7% were classified as α-chain variants and 93% as β-chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits being the most prevalent. We also documented 20 homozygous hemoglobinopathies and 36 compound/double heterozygous hemoglobinopathies. ConclusionA wide diversity of hemoglobinopathies is found in the Northern Alberta population, 80% of the hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals for HbF and HbA2 were established.

Double heterozygous HbQ India/HbD Punjab hemoglobinopathy: A rare case report

Hemoglobinopathies constitute the most common genetic diseases in the world. In India, both beta-thalassemia and structural hemoglobin variants, such as hemoglobin S (HbS), hemoglobin D (HbD), and hemoglobin E (HbE), are common and pose significant health problem, these variants show heterozygous state along with beta-thalassemia. Compound heterozygosity among hemoglobin variants is very rare. Cation-exchange high-performance liquid chromatography (CE HPLC) provides accurate and reliable diagnosis of various hemoglobin variants. Here, we report an index case of double heterozygous hemoglobinopathy, hemoglobin Q (HbQ) India/HbD Punjab (ααQ India-ββD Punjab) using CE HPLC. This is the fifth report of double heterozygosity for HbQ India/HbD Punjab globally and fourth case report from India to the best of our knowledge.

1000 Renal Tubular Function in Minor Thalassemia

β - Thalassemia minor is a common heterozygous hemoglobinopathy that is characterized by both microcytosis and hypochromia. It has been postulated that low grade hemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with β - thalassemia minor. The aim of this study is to investigate the renal tulbar function in children with β - thalassemia minor and to determine its possible harmful effects. Methods: The study was conducted on 50 children (22 male and 28 female) at the age of years (range 4-19 years) with β - Thalassemia minor. A control group was formed with 50 healthy children whose ages and sexes match those in the first group. Blood and 24-hour urine samples were obtained for hematologic and biochemical analysis. Results: There was statistically significant difference among the two groups in terms of the results of FEUA (%), TPR (%), FEk(%), GFR, Urine uric Acid, serum Mg (P < 0/05). But other significant signs of renal tubulopathy such as hypercalciuria, and tubular proteinuria (β2 - microglobolinuria) were not seen. Conclusion: On the contrary of children with β - Thalassemia major, renal tubular dysfunction is not common in children with β - Thalassemia minor. . Alsow it suggested that in future studies to confirm renal tubular disfanction should be considered specific test such as NAG measurement and specific parameter of oxidative stress such as urin zinc level (indirect evidence of oxidative stress).

Cytomorphologic signs of severe pernicious anemia obscured in a patient with heterozygous hemoglobin Stanleyville II

Here, we report a rare coincidence of heterozygous hemoglobinopathy (Hb) Stanleyville II and severe pernicious anemia due to autoimmune gastritis. Hb Stanleyville II is characterized by a single base exchange (AAC-->AAA) resulting in a substitution Asn --> Lys at position 78 of hemoglobin alpha2-chain. Under normal conditions this hemoglobinopathy does not cause any symptoms even if present as homozygous variant. However, in our case diagnosis of pernicious anemia was hampered by the absence of typical erythrocytic macrocytosis and hyperchromasia. In addition, interpretation of bone marrow smears was difficult as characteristic findings for pernicious anemia were little pronounced. All known reasons for the absence of typical cytomorphologic signs in pernicious anemia as underlying iron deficiency and thalassemia could be excluded.

Variable Efficacy of Recombinant Human Erythropoietin in Anemic Pregnant Women with Different Forms of Heterozygous Hemoglobinopathy

Objective: The aim of this study was to determine the response to recombinant human erythropoietin (rhEPO) in anemic pregnant women with heterozygous hemoglobinopathies. Methods: A prospective study including 19 consecutive pregnant women with anemia and heterozygous hemoglobinopathy was performed. Treatment wasdivided into two phases: the initial low-dose phase and the subsequent high-rhEPO phase. In the initial phase, 3 × 10,000 U of rhEPO was administered with intravenous iron sucrose. In patients showing a poor response (Hb increase <1 g/dl) to low-dose rhEPO, the rhEPO dose was increased to 20,000 U per treatment in the subsequent phase. Results: All patients showed stimulation of erythropoiesis as evidenced by an increase in hemoglobin. In 13 patients, a good response to therapy was observed (mean Hb increase 1.6 ± 0.5 g/dl). In 6 patients, resistance to rhEPO was noted (mean Hb increase 0.5 ± 0.5 g/dl). The mean gestational age at the start of therapy was 28 weeks of gestation and at the end 32 weeks. The mean duration of a complete therapy was 3.5 weeks (range 2–4.5 weeks). If calculated for body weight, the initial low- rhEPO dose of 160.4 ± 30.6 U/kg body weight/treatment was increased to 320.9 ± 61.2 U/kg body weight/treatment in the subsequent phase. Conclusion: Response to rhEPO treatment differs widely in anemic pregnant patients with heterozygous hemoglobinopathy. Resistance was observed in anemic pregnant patients with the β-thalassemia trait originally from the Mediterranean region.

Prevalencia de hemoglobinopatías en mujeres gestantes en el área sanitaria de Lanzarote

The aim of this study is to analyze the global prevalence of carriers of heterozygous hemoglobinopathies among pregnant women settled in Lanzarote.A epidemiologic cross-sectional observational investigation was undertaken to study the prevalence of hemoglobinopathies in 2,436 pregnant women in Lanzarote. The techniques of primary screening were hemoglobin electrophoresis on cellulose acetate at alkaline pH for the detection of hemoglobin variants, and the quantification of HbA2 and HbF for the diagnosis of b thalassemia trait. The study to confirm the diagnosis of structural hemoglobinopathies was based on hemoglobin electrophoresis on citrate agar at acid pH, isolectric focusing and high-performance liquid chromatography (HPLC). The molecular characterization of b thalassemia trait (HbA2 >3.5%) was carried out by techniques using a real time PCR procedure with specific fluorescently labelled hybridization probes and allele-specific amplification (PCR-ARMS).The global prevalence of hemoglobinopathies was 11.90 corresponding to 9.44 for structural hemoglobinopathies and 2.46 for heterozygous b thalassemias. A variant hemoglobin was detected on 23 women and the distribution was as follows: thirteen carriers of hemoglobin S, seven HbC trait, two HbD trait and one "unstable" hemoglobin. 82.6% of the variant hemoglobins found were from migrant population from Africa and America.The high prevalence of carriers of structural hemoglobinopathies in Lanzarote justifies the initiation of programs for screening for hemoglobinopathies to prevent the emergence of severe states causing disease.

Maternal and Perinatal Pregnancy Outcome in Women With Heterozygous Hemoglobinopathies

Maternal and Perinatal Pregnancy Outcome in Women With Heterozygous Hemoglobinopathies

Hemoglobin S/OARAB: Thirteen new cases and review of the literature

Hemoglobin S/OArab (Hb S/OArab) is a rare compound heterozygous hemoglobinopathy characterized by the presence of two variant β-globin chains: β6Glu → Val (Hb S) and β121Glu → Lys (Hb OArab). The diagnosis of Hb S/OArab requires electrophoresis on both cellulose acetate and citrate agar, since Hb OArab co-migrates with Hb C at alkaline pH and close to Hb S at acidic pH. To date only case reports and small series of patients with Hb S/OArab have been described. To better characterize the clinical and laboratory aspects of this unusual disorder, we reviewed the Duke University Medical Center experience. We identified 13 African-American children and adults with Hb S/OArab ranging in age from 2.7 to 62.5 years. All patients had hemolytic anemia with a median Hb of 8.7 gm/dL (range 6.1–9.9 gm/dL), and a median reticulocyte count of 5.8% (range 1.2–10.3%). The peripheral blood smear typically showed sickled erythrocytes, target cells, polychromasia, and nucleated red blood cells. All 13 patients have had significant clinical sickling events including acute chest syndrome (11), recurrent vasoocclusive painful events (10), dactylitis (7), gallstones (5), nephropathy (4), aplastic crises (2), avascular necrosis (2), leg ulcers (2), cerebrovascular accident (CVA) (1), osteomyelitis (1), and retinopathy (1). Four patients have died, including two from pneumococcal sepsis/meningitis at ages 5 and 10 years, one of acute chest syndrome at age 14 years, and one of multiorgan failure at age 35 years. We conclude that Hb S/OArab disease is a severe sickling hemoglobinopathy with laboratory and clinical manifestations similar to those of homozygous sickle cell anemia. Am. J. Hematol. 60:279–284, 1999. © 1999 Wiley-Liss, Inc.