BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor, and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.
alpha-Thalassemia ; Anemia, Hemolytic, Congenital ; beta-Thalassemia ; Diagnostic Tests, Routine ; Erythrocytes ; Flow Cytometry ; Globins ; Hematology ; Hemoglobinopathies ; Hemoglobins ; Humans ; Korea ; Prevalence ; Spherocytosis, Hereditary ; Thalassemia ; Surveys and Questionnaires

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder. There are more than 400 million people worldwide with G6PD deficiency, and its distribution is similar to that of malaria. G6PD deficiency is an X-linked recessive disorder. Most patients with G6PD deficiency may be asymptomatic throughout their lives. They may present as neonatal jaundice, or acute and chronic hemolysis. The most important point in the management of G6PD deficiency is to avoid oxidative stress. The prevalence of G6PD deficiency in Korea is about 0.9%. However, a nationwide survey has revealed that the number of patients with enzymopathy is increasing. Immigration of different ethnicities into Korea, and the rise of interracial marriages will likely lead to an increase in the number of patients with G6PD deficiency.
Anemia, Hemolytic, Congenital ; Anemia, Hemolytic, Congenital Nonspherocytic ; Emigration and Immigration ; Favism ; Glucosephosphate Dehydrogenase ; Glucosephosphate Dehydrogenase Deficiency ; Hemolysis ; Humans ; Infant, Newborn ; Jaundice, Neonatal ; Korea ; Malaria ; Marriage ; Oxidative Stress ; Prevalence ; Splenectomy

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.
Adult ; alpha-Thalassemia ; Anemia, Hemolytic, Congenital* ; beta-Thalassemia ; Bilirubin ; Cell Membrane ; Diagnosis ; Elliptocytosis, Hereditary ; Erythrocyte Indices ; Female ; Hemoglobinopathies ; Humans ; Internal Medicine ; Jaundice ; Korea* ; L-Lactate Dehydrogenase ; Male ; Oxidoreductases ; Pallor ; Pathology, Molecular ; Pediatrics ; Phosphopyruvate Hydratase ; Prevalence ; Pyruvate Kinase ; Reticulocyte Count ; Retrospective Studies* ; Sex Ratio ; Surveys and Questionnaires

No abstract available.
Anemia, Hemolytic, Congenital Nonspherocytic*

To understand the hemolytic anemia (HA) in children, the diagnostic approach and management of hereditary and acquired HA are described. The hereditary hemolytic anemia (HHA) can be classified according to the pathogenesis into three types:RBC membrane defects, hemoglobinopathies, and RBC enzymopathies. Clinical characteristics, laboratory findings and molecular defects of these three types are presented briefly. In Korea, HHA due to the RBC membrane defect, hereditary spherocytosis had been reported often but HHA due to hemoglobinopathies and RBC enzymopathies had been thought to be relatively rare. With recent development in the molecular diagnosis, beta thalassemia, mostly heterozygote, G6PD and pyruvate kinase deficiency have been reported with gene characterization. If the patients with microcytic hypochromic anemia show unproportionally low MCV or MCH or refractory to the iron therapy, hemoglobin electrophoresis and gene analysis for thalassemia or other unstable hemoglobinopathies need to be done accordingly. The global movement of the population especially from the region prevalent of hemoglobinopathies or enzymopathies to Korea warrants considering broad spectrum of etiology for the diagnosis of HHA. Aquired HA resulting from extracellular factors such as autoimmune HA from warm antibody, cold agglutinin and paroxysmal cold hemoglobinuria as well as nonimmune HA are described briefly.
Anemia, Hemolytic* ; Anemia, Hemolytic, Autoimmune ; Anemia, Hemolytic, Congenital ; Anemia, Hypochromic ; beta-Thalassemia ; Child ; Diagnosis ; Electrophoresis ; Hemoglobinopathies ; Hemoglobinuria, Paroxysmal ; Heterozygote ; Humans ; Iron ; Korea ; Membranes ; Pediatrics* ; Pyruvate Kinase ; Thalassemia

The hereditary hemolytic anemia (HHA) can be classified into three types according to the pathogenesis: RBC membrane defects, hemoglobinopathies, and RBC enzymopathies. Clinical characteristics of these three types of HHA are presented briefly in this paper. In Korea, HHA due to RBC membrane defect such as hereditary spherocytosis had been relatively well recognized, while HHA due to hemoglobinopathies and RBC enzymopathies had been considered rare. However, with the recent development of molecular testing, beta thalassemia, G6PD and pyruvate kinase deficiency have been reported with identification of disease-causing mutations. If a patient with microcytic hypochromic anemia shows unproportionally low MCV or MCH or refractory to iron therapy, hemoglobin electrophoresis and gene study for thalassemia or other unstable hemoglobinopathies are needed. It should be noted that the recent population migration to Korea from the regions where hemoglobinopathies or enzymopathies are prevalent warrants considering a broad spectrum of etiologies for the diagnosis of HHA.
Anemia, Hemolytic, Congenital* ; Anemia, Hypochromic ; beta-Thalassemia ; Diagnosis ; Electrophoresis ; Hemoglobinopathies ; Humans ; Iron ; Korea ; Membranes ; Pyruvate Kinase ; Thalassemia

Hemoglobins, Abnormal ; Humans ; alpha-Thalassemia ; complications ; beta-Thalassemia ; complications

OBJECTIVE: To investigate the gene-carrying rate and genetic types of thalassemia among the couples of child-bearing age in Ding'an, Hainan province. METHODS: A total of 1742 couples at child bearing age in the region were screened for thalassemia by detecting the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV). If the sample data of either spouse of couples was tested as MCV＜82 fl and /or MCH＜27 pg, both samples of the couple would be further assayed by hemoglobin electrophoresis. Those samples of HbA2 2.5 % or HbA2＞3.5 % were judged as positive in the preliminary screening, then subjected to genetic diagnosis of thalassemia. RESULTS: 478 cases out of 1 742 couples of child bearing age were diagnosed as thalassemia gene mutation, and the gene-carrying rate was 13.72 %. In those carriers, 42 couples were diagnosed with the same type of thalassemia, accounting for 3.67 %. The gene-carrying rate of α-thalassemia, β-thalassemia and αβ-thalassemia was 9.56%, 3.10% and 1.06 % respectively. CONCLUSION The Ding'an area in Hainan Province is an area with high incidence of thalassemia, and the main genotype is α-thalassemia, showing a distribution of local characteristics. The government should make efferts to popularise the screening for thalassemia, so as to effectively prevent the birth of children with thalassemia major.
Erythrocyte Indices ; Genetic Testing ; Heterozygote ; Humans ; alpha-Thalassemia ; beta-Thalassemia

OBJECTIVE: To analyze the genotype and hematological characteristics of children with αβ-thalassemia in Shenzhen area of China. METHODS: The erythrocyte parameters and hemoglobin components of the children were determined by blood routine examination and capillary electrophoresis (CE). Reverse dot blot (RDB) -polymerase chain reaction (PCR) was used to determine gene mutations in α- and β-thalassemia children. The Gap-PCR was used to determine the gene deletion of α-thalassemia children，while specimens suspected HKαα were determined with nested PCR. RESULTS: Total of 29 complex genotypes were detected from 74 cases of αβ-thalassemia, among which 1 case was determined as β-thalassemia with αααanti4.2/αα and 5 cases were double heterozygous β-thalassemia combining α-thalassemia with intermediate phenotype. 1 case of β-28/βcap+40-43 double heterozygotes combined with --/αα and the other 62 cases were characterized by light β-thalassemia, 2 cases ofβCAP+40-43/βN with --/αα showed light α-thalassemia. CONCLUSION The genotypes of αβ-thalassemia in Shenzhen area of China are complex and diverse. The common complex genotypes are similar to those of simple β-thalassemia. If the genotype and phenotype are not consistent, the existence of rare genotype should be considered.
Child ; China ; Genotype ; Humans ; Phenotype ; alpha-Thalassemia ; beta-Thalassemia

OBJECTIVE: To investigate the genetic carrier rate of thalassemia and its gene mutation types as well as the distribution characteristics among the people in Lingshui Li autonomous county of Hainan province, so as to provide the basis for making the prevention programs of thalassemia in administrative departments. METHODS: Samples were collected from couples undergoing premarital and pregestational screenings, in which the positive ones in preliminary screening were further tested by genetic diagnoses and the genotypes were analyzed. RESULTS: The rate of thalassemia gene carriers was 19.41% （274/1412） of the couples of childbearing age in Lingshui Li autonomous County of Hainan Province. In these carriers,α-thalassemia accounted for 83.21%（228/274）, β-thalassemia for 8.03%（22/274）, and both α-and β-thalassemia gene accounted for 8.76% （28/274）. CONCLUSION The carrying rate of thalassemia gene in population Lingshui Li autonomous county of Hainan province is high, and its distribution has geographical characteristics,the major type is α-thalassemia. Blood screening and genetic diagnosis of thalassemia should be strengthened, and corresponding measures should be taken to reduce its gene frequency.
China ; Genetic Testing ; Genotype ; Heterozygote ; Humans ; alpha-Thalassemia ; beta-Thalassemia