Clinical and gene mutation characteristics of patients with hereditary ellipsocytosis: nine cases report and literature review / 中华血液学杂志

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.

Clasificación y métodos de diagnóstico de las membranopatías / Classification and diagnostic methods of membranopathies

Introducción: Las membranopatías son anemias hemolíticas hereditarias debidas a anomalías cualitativas o deficiencias cuantitativas de las proteínas del citoesqueleto del glóbulo rojo. Objetivo: Actualizar el diagnóstico de las membranopatías con la inclusión de las últimas recomendaciones del comité de grupos de expertos a nivel nacional e internacional. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico, de artículos publicados en los últimos cinco años. Análisis y síntesis de la información: Las enfermedades de mayor interés clínico son: la esferocitosis, la eliptocitosis y la estomatocitosis hereditaria. Estas en general se heredan con carácter autosómico dominante pero existen formas que se transmiten con carácter recesivo, sin descartar posible mutación de novo. Para su diagnóstico se utilizan pruebas que incluyen el estudio de la morfología de los glóbulos rojos, la fragilidad osmótica, la lisis de glicerol acidificado, la criohemólisis hipertónica, la prueba de unión a la eosina-5'-maleimida por citometría de flujo, la electroforesis en gel de poliacrilamida con dodecilsulfato sódico y la ectacitometría. Conclusiones: Las membranopatías pueden sospecharse de manera preliminar teniendo en cuenta algunas alteraciones de la morfología eritrocitaria, aunque el diagnóstico se basa en estudios familiares y otros de carácter confirmatorio de la enfermedad, como los estudios moleculares. Los profesionales de la salud que atienden a pacientes jóvenes con anemia deben considerar la posibilidad de una anemia hemolítica por trastornos de la membrana eritrocitaria(AU)

ABSTRACT Introduction: Membranopathies are inherited hemolytic anemias due to qualitative abnormalities or quantitative deficiencies of red blood cell cytoskeletal proteins. Objective: to update the diagnosis of membranopathies with the inclusion of the latest recommendations from the committee of expert groups at the national and international level. Methods: A review of the literature in English and Spanish was carried out, through the PubMed website and the academic search engine Google, in articles published in the last five years. Analysis and synthesis of information: The diseases of greatest clinical interest are: spherocytocis, elliptocytosis and hereditary stomatocytosis. These are generally inherited with an autosomal dominant character but there are forms that are transmitted recessively, without ruling out a possible de novo mutation. For its diagnosis, tests are used that include the study of red blood cell morphology, osmotic fragility, acidified glycerol lysis, hypertonic cryohemolysis, eosin-5'-maleimide binding test by flow cytometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis and ectacytometry. Conclusions: Membranopathies can be preliminarily suspected taking into account some alterations in erythrocyte morphology, although the diagnosis is based on family studies and others confirming the disease, such as molecular studies. Healthcare professionals caring for young patients with anemia should consider the possibility of hemolytic anemia due to red cell membrane disorders(AU)

Anemias hemolíticas hereditarias por defectos en la membrana de los eritrocitos / Hereditary hemolytic anemias due to erythrocyte membrane defects

Introducción: La membrana de los eritrocitos, al igual que las membranas de otros tipos celulares, está compuesta por una bicapa lipídica que es estabilizada por proteínas específicas, glucolípidos y otras moléculas especializadas. Las mutaciones producidas en los genes que codifican y regulan estas proteínas y sus interacciones producen cambios en la forma de los eritrocitos y son causa de anemias hemolíticas hereditarias. Objetivo: Describir las peculiaridades moleculares, clínicas y el diagnóstico de laboratorio de las principales anemias hemolíticas hereditarias por defectos en la membrana de los eritrocitos. Métodos: Se realizó una revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las mutaciones que afectan la membrana de los eritrocitos son variadas y heterogéneas. El efecto sobre el fenotipo puede ser clasificado en cinco categorías principales: esferocitosis hereditaria; eliptocitosis hereditaria y piropoiquilocitosis hereditaria; ovalocitosis del sureste asiático; acantocitosis hereditaria y estomatocitosis hereditaria. Conclusiones: La cuidadosa observación de la morfología de los eritrocitos en extendidos de sangre periférica y los estudios moleculares permiten realizar un diagnóstico certero, además de confirmar la correlación genotipo/fenotipo en estas enfermedades(AU)

Introduction: The erythrocyte membrane, like the membranes of other cell types, is composed of a lipid bilayer that is stabilized by specific proteins, glycolipids and other specialized molecules. Mutations in the genes that encode and regulate these proteins and their interactions cause changes in the shape of erythrocytes and are the cause of hereditary hemolytic anemias. Objective: To describe the molecular and clinical peculiarities and the laboratory diagnosis of the main hereditary hemolytic anemias due to defects in the erythrocyte membrane. Methods: A literature review was carried out, in English and in Spanish, through the PubMed website and the Google Scholar search engine, of articles published in the last ten years. An analysis and summary of the revised bibliography was made. Information analysis and synthesis: Mutations affecting the erythrocyte membrane are varied and heterogeneous. The effect on the phenotype can be classified into five main categories: hereditary spherocytosis, hereditary elliptocytosis and hereditary pyropoikilocytosis, Southeast Asian ovalocytosis, hereditary acantocytosis, and hereditary stomatocytosis. Conclusions: Careful observation of erythrocyte morphology in peripheral blood smears and molecular studies allow an accurate diagnosis, in addition to confirming the genotype-phenotype correlation in these diseases(AU)

Hereditary Elliptocytosis: An Incidental Finding in a 6-year-old Child.

A case of hereditary elliptocytosis (HE) in a 6-year-old child diagnosed as an incidental finding has been presented.

Eliptocitose hereditária diagnosticada em paciente idosa: relato de caso / Hereditary elliptocytosis diagnosed in elderly patient: case report

JUSTIFICATIVA E OBJETIVOS: A anemia é extremamente prevalente na população idosa, implicando na necessidadede uma investigação aprofundada, com o intuito de se obter melhora na qualidade de vida desses pacientes. A eliptocitose hereditária, que é caracterizada pela presença de eritrócitos em forma elíptica no sangue periférico, raramente é determinante de anemia sintomática em idosos. O objetivo deste estudo foi relatar um caso de eliptocitose hereditária como causa de anemia sintomática em paciente idosa e discutir seus aspectos clínicos, evolutivos, diagnósticos e terapêuticos, ressaltando a importância da avaliação criteriosa de alterações clínicas sugestivas de anemia em idosos. RELATO DO CASO: Paciente do sexo feminino, 67 anos, que se apresentou com anemia hemolítica (hemoglobina reduzida e reticulocitose) sintomática (dores nas pernas, astenia e fadiga) e diagnosticada com eliptocitose hereditária através da visualização de 40% de eliptócitos na análise do esfregaço de sangue periférico, após vários anos de evolução clínica. Recebeu ácido fólico apresentando melhora clínica e dos valores hematimétricos. CONCLUSÃO: Embora a eliptocitose hereditária seja rara, deve fazer parte dos diagnósticos diferenciais de anemia sintomática em idosos, principalmente na vigência de sinais de hemólise (reticulócitos aumentados). A análise do esfregaço sanguíneo na busca de eliptócitos é essencial para a confirmação diagnóstica.

BACKGROUND AND OBJECTIVES: Anemia is a common condition in the older population, implying the need for a thorough investigation in order to achieve improved quality of life for these patients. Hereditary elliptocytosis, characterized by the presence of elliptically red cells on peripheral blood smear, has been rarely described as a determinant of symptomatic anemia in the elderly. The aim of this study was to report a case of hereditary elliptocytosis as a cause of symptomatic hemolytic anemia in an elderly patient and to discuss its clinical, evolutionary, diagnostic, and therapeutic aspects, emphasizing the importance of a careful assessment of clinical alterations suggestive of anemia in older persons. CASE REPORT: A female patient, 67 years old, who presented with symptomatic (leg pain, weakness and fatigue) hemolytic anemia (reduced hemoglobin and reticulocytosis) was diagnosed with hereditary elliptocytosis by visualization of 40% of elliptical erythrocytes in the analysis of peripheral blood smear, after several years of clinical evolution. She was given folic acid, presenting clinical and hematological values improvement. CONCLUSION: Although the hereditary elliptocytosis is rare, it should be part of the differential diagnosis of symptomatic anemia in older persons, especially in the presence of hemolytic signs (increased reticulocytes). Analysis of peripheral blood smear for search for elliptocytes is essential for diagnosis.

Transient Elliptocytosis Associated with Acute Lymphoblastic Leukemia / 대한혈액학회지

Elliptocytosis has been known to be a rare disease, especially in oriental people. Most of them are transmitted as an autosomal dominant trait but we experienced one case of transient elliptocytosis associated with acute lymphoblastic leukemia by morphologic examination of the peripheral blood and bone marrow biopsy. The results of the peripheral blood smears of the patient and his family are as follows : he showed about 50~60% of elliptocytes and anemia without hemolytic event; his family, however, showedno sign of elliptocytosis. The patient was treated for acute lymphoblastic leukemia. On follow-up check after one month, the peripheral blood showed almost normal RBC morphology. Therefore, we diagnosed this case as transient elliptocytosis associated with acute leukemia. So we report a case of transient elliptocytosis associated with acute leukemia with a brief review of the relevant literature.

SDS-PAGE Analysis of Red Cell Membrane Proteins in Hereditary Hemolytic Anemia / 대한혈액학회지

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.