Hereditary elliptocytosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Niyousha Danesh M.D., M.P.H.
Overview
Hereditary elliptocytosis is one of the most common red blood cell membrane disorder in which a large proportion of the erythrocytes (i.e. red blood cells) are elliptical rather than biconcave disc-shaped and it shortens RBC survival. It is also known as ovalocytosis. The main disorder in Hereditary elliptocytosis is cytoskeletal proteins defect,which influence the biconcave appearance of RBCs. patients with HE are usually asymptomatic however they present sometime hemolysis and haemolytic anaemia.[1]
Historical Perspective
RBC anomaly in Hereditary elliptocytosis was first observed in 1860 by Goltz, [2]and Elliptocytosis, elliptical shape of RBCs was described in 1904 by Dresbach. [3] Bishop recognized the familial inheritance as autosomal dominant of HE in 1914 and Hunter and Adams affirmed it's hereditary condition in 1929.[2] Recent studies demonstrate that, the severity of symptoms in patients with Hereditary elliptocytosis is variable and it can be related to genetic variations.[4]
Classification
Pathophysiology
Hereditary elliptocytosis is commonly an autosomal dominant (AD) disorder, in which mutations in alpha-spectrin or beta-spectrin occur, that leads to quantity or structural defects of the cytoskeletal proteins in RBCs. Other cytoskeletal proteins such as glycophorin and band 4.1 can also be mutated in this disease.[5]
Another form of inheritance in HE is autosomal recessive (AR) ,it is called hereditary pyropoikilocytosis (HPP), and rarely spontaneous mutations have been reported.[1]
Quality and quantity defects of the cytoskeletal proteins are responsible in Hereditary elliptocytosis. These cytoskeletal proteins are necessary for maintenance of RBCs structure, specially their biconcave morphology.In this disease the protein scaffolding in the inner side of RBC is influenced and results in defective RBCs membrane
Hereditary elliptocytosis is commonly inherited as autosomal dominant. The only exception is autosomal recessive inheritance of hereditary pyropoikilocytosis (HPP). The spontaneous mutations occurs rarely.
The RBC membrane consists of a lipid bilayer and a protein cytoskeleton, which increase RBC resistance, Spectrin is one of the main part of this scaffold and has 2 chains, alpha and beta. Separate genes encode alpha and beta chains and after being twisted together, they create an elongated heterodimer. These heterodimers build tetramers in the head part and they are linked to other cytoskeletal proteins at the tail regien,protein 4.1 and actin. Then protein 4.1 and actin bind to glycophorin A, band 3, and glycophorin C, the transmembrane proteins, connecting the scaffold to the lipid bilayer.
Mutations involved in the pathogenesis of HE can occur in each one of the cytoskeletal proteins,such as spectrins, band 4.1 or glycophorin C.
These mutations affect mainly alpha- and beta-spectrin,impairing of the spectrin heterodimer formation. The combination of heterodimer and the lipid anchoring complex can also be influenced.
Normal erythrocytes remain in the blood circulation for 120 days and they can maintain their elastic recoil and their discoid shape after passing through the capillaries in microcirculation , yet the elliptical shape of RBCs reduces the elasticity of RBCs, so their discoid shape is damaged and their ability to pass through 2 micron capillaries is reduced, so they are trapped and removed by the spleen. The reduction in surface to volume ratio of RBCs and their premature destruction leads to extravascular hemolysis and the clinical signs and symptoms of these disease.[6][7]
Causes
Differentiating Hereditary elliptocytosis overview from Other Diseases
Epidemiology and Demographics
Risk Factors
Hereditary elliptocytosis is one of the most common RBC membrane disorders worldwide,and the incidence of HE is 25-50 per 100,000 individuals.
The prevalence of Hereditary elliptocytosis is 50 out of 100,000 affected cases in Northern European countries and North America.[1]
In endemic areas for malaria,the incidence of HE is notably higher, this incidence ranges from a low of 600 per 100,000 persons in equatorial Africa to a high of 30,000 per 100,000 persons in Malayan aborigines.
This large number of prevalence is because of relative resistance of elliptocytes against malaria in the endemic areas.
As many patients with HE are asymptomatic, the true incidence is not known.[8]
Screening
Natural History, Complications, and Prognosis
Natural History
Complications
Prognosis
Diagnosis
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Prevention
References
- ↑ 1.0 1.1 1.2 Da Costa L, Galimand J, Fenneteau O, Mohandas N (2013). "Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders". Blood Rev. 27 (4): 167–78. doi:10.1016/j.blre.2013.04.003. PMID 23664421.
- ↑ 2.0 2.1 "Hereditary elliptocytic anaemia" (PDF).
- ↑ Dresbach M (1904). "ELLIPTICAL HUMAN RED CORPUSCLES". Science. 19 (481): 469–70. doi:10.1126/science.19.481.469. PMID 17730874.
- ↑ Tse WT, Lux SE (1999). "Red blood cell membrane disorders". Br J Haematol. 104 (1): 2–13. PMID 10027705. Check
|pmid=value (help). - ↑ Harper SL, Sriswasdi S, Tang HY, Gaetani M, Gallagher PG, Speicher DW (2013). "The common hereditary elliptocytosis-associated α-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation". Blood. 122 (17): 3045–53. doi:10.1182/blood-2013-02-487702. PMC 3811177. PMID 23974198.
- ↑ Christensen RD, Nussenzveig RH, Reading NS, Agarwal AM, Prchal JT, Yaish HM (2014). "Variations in both α-spectrin (SPTA1) and β-spectrin ( SPTB ) in a neonate with prolonged jaundice in a family where nine individuals had hereditary elliptocytosis". Neonatology. 105 (1): 1–4. doi:10.1159/000354884. PMID 24193021.
- ↑ "Hereditary Elliptocytosis".
- ↑ Keklik M, Unal A, Sivgin S, Kontas O, Eroglu E, Yilmaz S; et al. (2014). "The coincidence of familial mediterranean Fever and hypereosinophilia in a patient with hereditary elliptocytosis". Indian J Hematol Blood Transfus. 30 (Suppl 1): 138–41. doi:10.1007/s12288-013-0296-6. PMC 4192255. PMID 25332561.