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Lancet (London, England) Oct 2008Hereditary spherocytosis is a common inherited disorder that is characterised by anaemia, jaundice, and splenomegaly. It is reported worldwide and is the most common...
Hereditary spherocytosis is a common inherited disorder that is characterised by anaemia, jaundice, and splenomegaly. It is reported worldwide and is the most common inherited anaemia in individuals of northern European ancestry. Clinical severity is variable with most patients having a well-compensated haemolytic anaemia. Some individuals are asymptomatic, whereas others have severe haemolytic anaemia requiring erythrocyte transfusion. The primary lesion in hereditary spherocytosis is loss of membrane surface area, leading to reduced deformability due to defects in the membrane proteins ankyrin, band 3, beta spectrin, alpha spectrin, or protein 4.2. Many isolated mutations have been identified in the genes encoding these membrane proteins; common hereditary spherocytosis-associated mutations have not been identified. Abnormal spherocytes are trapped and destroyed in the spleen and this is the main cause of haemolysis in this disorder. Common complications are cholelithiasis, haemolytic episodes, and aplastic crises. Splenectomy is curative but should be undertaken only after careful assessment of the risks and benefits.
Topics: Gallbladder Diseases; Hemolysis; Humans; Severity of Illness Index; Spherocytosis, Hereditary; Splenectomy
PubMed: 18940465
DOI: 10.1016/S0140-6736(08)61588-3 -
Acta Haematologica 2018With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1,... (Review)
Review
With the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.
Topics: Biomarkers; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Spherocytosis, Hereditary
PubMed: 29402830
DOI: 10.1159/000486229 -
British Journal of Haematology Nov 2020Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a...
Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease-causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 and SPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1-HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1-HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling.
Topics: Adolescent; Age Factors; Alleles; Blood Cell Count; Child; Child, Preschool; Combined Modality Therapy; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Male; Mutation; Phenotype; Retrospective Studies; Spherocytosis, Hereditary
PubMed: 32436265
DOI: 10.1111/bjh.16750 -
Pediatrics in Review May 2004
Review
Topics: Erythrocyte Transfusion; Erythrocytes; Humans; Infant, Newborn; Membrane Proteins; Mutation; Spherocytes; Spherocytosis, Hereditary; Splenectomy
PubMed: 15121908
DOI: 10.1542/pir.25-5-168 -
Clinics in Haematology Feb 1975
Review
Topics: Adolescent; Blood Transfusion; Cell Membrane; Child; Erythrocyte Aging; Female; Folic Acid; Humans; Jaundice; Male; Spherocytes; Spherocytosis, Hereditary; Spleen; Splenectomy; Splenomegaly
PubMed: 1102180
DOI: No ID Found -
American Family Physician Feb 1989Hereditary spherocytosis is the most common inherited anemia in persons of northern European descent. In 75 percent of cases, the condition is inherited in an autosomal... (Review)
Review
Hereditary spherocytosis is the most common inherited anemia in persons of northern European descent. In 75 percent of cases, the condition is inherited in an autosomal dominant fashion. Patients usually present with splenomegaly, jaundice and anemia. A deficiency of the cytoskeletal protein spectrin is believed to underlie this hemolytic state. Affected individuals display a tendency to form pigmented (bilirubin) gallstones. Splenectomy may be essentially curative in the majority of patients.
Topics: Diagnosis, Differential; Humans; Prognosis; Spherocytosis, Hereditary
PubMed: 2644787
DOI: No ID Found -
Transfusion Clinique Et Biologique :... Sep 2010Hereditary spherocytosis is a common hemolytic disorder characterized by a defect or deficiency in one or more of the proteins composing red blood cell membrane. As a...
Hereditary spherocytosis is a common hemolytic disorder characterized by a defect or deficiency in one or more of the proteins composing red blood cell membrane. As a result, red blood cells have an abnormal shape, higher metabolic requirements, and are prematurely trapped and destroyed in the spleen. Hereditary spherocytosis, including the very mild or subclinical forms, is the most common cause of non-immune hemolytic anemia among people of Northern European ancestry, with a prevalence of approximately 1 in 2000. However very mild forms of the disease may be much more common. Hereditary spherocytosis is inherited in a dominant fashion in 75% of cases, whereas the remaining are truly recessive cases and de novo mutations. This review reports current concepts on red cell membrane structure and it will attempt to clarify molecular defects leading to spherocyte and their consequences.
Topics: Anemia, Hemolytic; Anion Exchange Protein 1, Erythrocyte; Diagnosis, Differential; Erythrocyte Deformability; Erythrocyte Membrane; Europe; Genes, Dominant; Genes, Recessive; Humans; Membrane Proteins; Mutation; Spherocytosis, Hereditary; White People
PubMed: 20655264
DOI: 10.1016/j.tracli.2010.05.006 -
Blut 1970
Review
Topics: Adenosine Triphosphatases; Anemia; Cell Membrane Permeability; Erythrocyte Aging; Erythrocytes; Erythropoiesis; Glycolysis; Humans; Hyperbilirubinemia; Jaundice; Osmotic Fragility; Ouabain; Phospholipids; Reticulocytes; Sodium; Spherocytosis, Hereditary; Splenectomy; Splenomegaly
PubMed: 4245218
DOI: 10.1007/BF01632249 -
Blood Reviews Jul 2013Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell... (Review)
Review
Hereditary spherocytosis and elliptocytosis are the two most common inherited red cell membrane disorders resulting from mutations in genes encoding various red cell membrane and skeletal proteins. Red cell membrane, a composite structure composed of lipid bilayer linked to spectrin-based membrane skeleton is responsible for the unique features of flexibility and mechanical stability of the cell. Defects in various proteins involved in linking the lipid bilayer to membrane skeleton result in loss in membrane cohesion leading to surface area loss and hereditary spherocytosis while defects in proteins involved in lateral interactions of the spectrin-based skeleton lead to decreased mechanical stability, membrane fragmentation and hereditary elliptocytosis. The disease severity is primarily dependent on the extent of membrane surface area loss. Both these diseases can be readily diagnosed by various laboratory approaches that include red blood cell cytology, flow cytometry, ektacytometry, electrophoresis of the red cell membrane proteins, and mutational analysis of gene encoding red cell membrane proteins.
Topics: Ankyrins; Elliptocytosis, Hereditary; Erythrocytes; Humans; Spherocytosis, Hereditary
PubMed: 23664421
DOI: 10.1016/j.blre.2013.04.003 -
Haematologica Mar 1998Resistance and elastic deformability of red cells are due to a protein network (cytoskeleton) that laminates the lipid bilayer and to proteins that span the latter. All... (Review)
Review
Resistance and elastic deformability of red cells are due to a protein network (cytoskeleton) that laminates the lipid bilayer and to proteins that span the latter. All proteins are interconnected. Their structure as well as the structure of the corresponding genes are now well known. Hereditary spherocytosis (HS) is the most common hemolytic anemia due to a red cell membrane defect. It derives from alterations of the following genes: ANK1, EPB3, ELB42, SPTA1 and SPTB. This condition is clinically, biochemically and genetically heterogeneous. The osmotically fragile spherocytes are selectively trapped in the spleen and destroyed. Increased red blood cell destruction causes the three main clinical signs of HS: anemia, jaundice and splenomegaly. In this review we analyze the most recent advances concerning the molecular basis and the clinical course of HS. In particular, we examine the major individual proteins that constitute the skeleton, which are now known to play an essential role in the pathogenesis of HS. This paper also includes a review of the therapeutical approach to HS. Concerning the diagnosis we provide a flow chart from the clinical aspects to the molecular diagnosis.
Topics: Erythrocytes; Family Health; Humans; Spherocytosis, Hereditary
PubMed: 9573679
DOI: No ID Found