Adolescent ; Adult ; Child ; Elliptocytosis, Hereditary ; diagnosis ; genetics ; Female ; Humans ; Male

Objective: To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. Methods: The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Results: Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. Conclusion: SPTA1 is the most common mutant gene in patients with HE.
Humans ; Mutation ; Elliptocytosis, Hereditary/metabolism* ; Erythrocyte Membrane/metabolism* ; Exons ; High-Throughput Nucleotide Sequencing ; Spherocytosis, Hereditary/metabolism*

BACKGROUND: Red cell membrane is a lipid bilayer laminated by the membrane cytoskeleton at the surface of inner monolayer. A class of hemolytic anemia, such as hereditary spherocytosis (HS) or hereditary elliptocytosis (HE) is mainly caused by the abnormalities of the protein components in the cytoskeleton, which is useful to diagnosis each disorder. We investigated red cell membrane protein defects in HS and HE using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). METHODS: We studied 10 normal healthy volunteers, 27 HS cases and 5 HE cases. Erythrocyte membrane proteins were prepared by hypotonic lysis, and fractionated by SDS-PAGE using both the Fairbanks system (3.5~17% exponential gradient gel), and the Laemmli system (4~17% linear gradient gel). Fractionated proteins were stained with Coomassie brilliant blue and scanned to quantitate each protein using a densitometer. RESULTS: We detected nine peaks in Fairbanks' gel and eight peaks in Laemmli's. We identified red cell membrane abnormalities in 18 of 27 HS patients (66.7%) : Spectrin deficiency alone was in 7.4% of HS cases (2/27), ankyrin deficiency alone in 29.6% (8/27), combined spectrin and ankyrin deficiency in 3.7% (1/27), band 3 deficiency in 11.1% (3/27) and protein 4.2 deficiency in 14.8% (4/27). In HE, three of five cases showed protein 4.1 deficiency. RBC membrane protein deficiencies were not observed in nine HS cases and two HE case. CONCLUSION: In HS, Ankyrin deficiency is the most common RBC membrane protein abnor mality, and protein 4.2 deficiency is more frequently found in Korean HS patients than in Caucasians. In HE patients, protein 4.1 deficiencies is the main red cell membrane protein defect, which is rarely reported in Caucasians.
Anemia, Hemolytic ; Anemia, Hemolytic, Congenital* ; Ankyrins ; Cell Membrane* ; Cytoskeleton ; Diagnosis ; Electrophoresis ; Electrophoresis, Polyacrylamide Gel* ; Elliptocytosis, Hereditary ; Erythrocyte Membrane ; Healthy Volunteers ; Humans ; Lipid Bilayers ; Membrane Proteins* ; Membranes ; Sodium ; Spectrin

No abstract available.
Adult ; Anemia/diagnosis ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Bone Marrow Cells/cytology/pathology ; Elliptocytosis, Hereditary/*diagnosis/*genetics/pathology ; Female ; Heterozygote ; Humans ; Infant, Newborn ; Mutation, Missense ; Republic of Korea ; Spectrin/chemistry/*genetics ; Splenomegaly/ultrasonography

Among the causes of pure red cell aplasia, human parvovirus B19 has been shown to be cytotoxic to erythroid progenitor cells in the bone marrow associated with chronic hemolytic anemia with rapidly dividing erythroids and persistently to be suppression of erythropoiesis in immunocompromised individuals related with failure to produce neutralizing antibody to the virus. In a patient with hereditary spherocytosis presenting acute onset of reticulocytopenia during hospitalization, who had shown severe anemia and prodromal symptoms including fever, fatigue and dizziness, infection of parvovirus Bl9 was proven by the presence of IgM and IgG antibodies to parvovirus Bl9, the detection of viral DNA using PCR technique in her serum and the decreased erythroid cells, especially late normoblasts in bone marrow, Also in the other who was diagnosed as hereditary elliptocytosis and complained of fever, headache, abdominal pain and diarrhea, an episode of reticulocytopenia and the nearly absence of late normoblasts in the bone marrow were observed. IgM antibodies to parvovirus Bl9 and the viral DNA were detected in her serum, too.
Abdominal Pain ; Anemia ; Anemia, Hemolytic ; Antibodies ; Antibodies, Neutralizing ; Bone Marrow ; Diarrhea ; Dizziness ; DNA, Viral ; Elliptocytosis, Hereditary* ; Erythroblasts ; Erythroid Cells ; Erythroid Precursor Cells ; Erythropoiesis ; Fatigue ; Fever ; Headache ; Hospitalization ; Humans* ; Immunoglobulin G ; Immunoglobulin M ; Parvovirus B19, Human ; Parvovirus* ; Polymerase Chain Reaction ; Prodromal Symptoms ; Red-Cell Aplasia, Pure

Among the causes of pure red cell aplasia, human parvovirus B19 has been shown to be cytotoxic to erythroid progenitor cells in the bone marrow associated with chronic hemolytic anemia with rapidly dividing erythroids and persistently to be suppression of erythropoiesis in immunocompromised individuals related with failure to produce neutralizing antibody to the virus. In a patient with hereditary spherocytosis presenting acute onset of reticulocytopenia during hospitalization, who had shown severe anemia and prodromal symptoms including fever, fatigue and dizziness, infection of parvovirus Bl9 was proven by the presence of IgM and IgG antibodies to parvovirus Bl9, the detection of viral DNA using PCR technique in her serum and the decreased erythroid cells, especially late normoblasts in bone marrow, Also in the other who was diagnosed as hereditary elliptocytosis and complained of fever, headache, abdominal pain and diarrhea, an episode of reticulocytopenia and the nearly absence of late normoblasts in the bone marrow were observed. IgM antibodies to parvovirus Bl9 and the viral DNA were detected in her serum, too.
Abdominal Pain ; Anemia ; Anemia, Hemolytic ; Antibodies ; Antibodies, Neutralizing ; Bone Marrow ; Diarrhea ; Dizziness ; DNA, Viral ; Elliptocytosis, Hereditary* ; Erythroblasts ; Erythroid Cells ; Erythroid Precursor Cells ; Erythropoiesis ; Fatigue ; Fever ; Headache ; Hospitalization ; Humans* ; Immunoglobulin G ; Immunoglobulin M ; Parvovirus B19, Human ; Parvovirus* ; Polymerase Chain Reaction ; Prodromal Symptoms ; Red-Cell Aplasia, Pure

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