Hereditary elliptocytosis (HE) encompasses a heterogeneous group of red blood cell membrane disorders caused by mutations affecting the erythrocyte membranes and cytoskeletal proteins. Most patients are asymptomatic while those with the more severe forms of HE exhibit significant hemolytic anemia.
Hereditary elliptocytosis (HE) is comprised of red blood cell (RBC) membrane disorders that differ genetically, biochemically, and clinically  . The elliptically shaped erythrocytes in HE develop as a result of mutations in genes encoding αlpha-spectrin, beta-spectrin, or cytoskeletal proteins such as band 4.1 and glycophorin   . Hence, the defective membrane scaffolding leads to less RBC resilience and deformability. Of importance, the severity of the disease is correlated with the cell's surface area loss .
There are three morphologic variants of HE: common HE, spherocytic elliptocytosis, and Southeast Asian ovalocytosis, which are all inherited in an autosomal dominant pattern  . Note that there is a severe subtype of common HE, known as hereditary pyropoikilocytosis (HPP), which exhibits an autosomal recessive mode of inheritance .
While more than 90% of patients with HE are asymptomatic, the clinical presentation is variable depending on the type  . Common HE, the predominant form, is typically clinically silent. If the hemolysis is significant, patients will display symptoms related to anemia.
HPP features hemolytic anemia in infants typically of African origin . These patients continue to have hemolytic anemia throughout life. Another subtype of common HE, neonatal poikilocytosis, is observed in African American neonates and infants, who manifest with significant hemolytic anemia that resolves during their first year.
Spherocytic elliptocytosis occurs in those with European ancestry and causes milder forms of hemolysis while Southeast Asian ovalocytosis is characterized by mild no or no hemolysis. The latter has a resistance to malaria.
Entire Body System
People with this disease can develop anemia, jaundice, and gallstones. Call your provider if you have jaundice that does not go away or symptoms of anemia or gallstones. [nlm.nih.gov]
If the hemolysis is significant, patients will display symptoms related to anemia. HPP features hemolytic anemia in infants typically of African origin. These patients continue to have hemolytic anemia throughout life. [symptoma.com]
It manifests as a severe hemolytic anemia with thermal instability of the red blood cells. (See Presentation and Workup .) Patients with HPP who develop severe hemolytic anemia require transfusion of packed red blood cells. [emedicine.medscape.com]
Parvoviral induced transient aplastic crisis in the form of sudden onset anemia is said to be a rare manifestation of this hereditary hemolytic anemia. [ncbi.nlm.nih.gov]
Symptoms may include: Fatigue Shortness of breath Yellow skin and eyes (jaundice). May continue for a long time in a newborn. An exam by your health care provider may show an enlarged spleen. [nlm.nih.gov]
Symptoms of anemia: fatigue, dizziness (MOST PATIENTS HAVE NO ANEMIA) Jaundice : increased unconjugated bilirubin in the blood (due to hemolysis) will result in physical findings of jaundice. [stepwards.com]
Symptoms Fatigue Shortness of breath Yellow skin and eyes (jaundice) - may continue for a long time in a newborn Exams and Tests An exam by your health care provider may show an enlarged spleen. [nicklauschildrens.org]
Symptoms Symptoms may include: Fatigue Shortness of breath Yellow skin and eyes (jaundice). May continue for a long time in a newborn. Exams and Tests An exam by your health care provider may show an enlarged spleen. [ufhealth.org]
These can include: Vague, poorly localized abdominal pain Fatigue and dyspnea Growth failure Leg ulcers Gallstones.. [slideshare.net]
Liver, Gall & Pancreas
Physical exam Individuals with hemolysis may exhibit signs such as pallor, scleral icterus, or splenomegaly. Rarely, patients will develop leg ulcers. [symptoma.com]
The proband presented with xanthochromia, scleral icterus in both eyes and slight redness in the pharynx. The liver and spleen were palpable at 2 cmunder the ribs, with a medium hardness, and were slightly obtuse on the edge. [spandidos-publications.com]
We assigned the gene for erythrocyte protein 4.1 to the short arm (p) of chromosome 1, within a region from band 32 to the terminus (1p32----1pter). [ncbi.nlm.nih.gov]
We assigned the gene for erythrocyte protein 4.1 to the short arm (p) of chromosome 1, within a region from band 32 to the terminus (1p32 1pter). [nejm.org]
The assessment for RBC membrane disorders includes the patient and family history, a full physical exam, and the appropriate investigations.
Key laboratory studies comprise a complete blood count (CBC), reticulocyte count, bilirubin, haptoglobin, lactate dehydrogenase (LDH), Coombs test, potassium, and a peripheral blood smear . Findings indicative of hemolysis include an elevated reticulocyte count, low levels of haptoglobin, and increased levels of LDH and indirect bilirubin.
In patients with HE, microscopic analysis of the peripheral blood will reveal approximately 25% elliptocytes although this is variable. Fragmented RBCs are also common  . Of note, there is no correlation between the proportion of elliptocytes and the degree of hemolysis.
The erythrocyte morphology of each form of HE varies. In patients with the subtype HPP, the smear reveals poikilocytes, microspherocytes, RBC fragments, as well as elliptocytes . Moreover, spherocytic elliptocytosis features the presence of both elliptocytes and spherocytes while Southeast Asian ovalocytosis is associated with elliptocytes characterized by a transverse slit that bisects the cell.
Another diagnostic method, gel electrophoresis, is used for identification of protein deficiencies and analysis of spectrin . Also, osmotic fragility is a useful test. In the typical form of HE, osmotic fragility is normal whereas it is elevated in cases with HPP and spherocytic elliptocytosis .
Osmotic gradient ektacytometry, the reference technique for diagnosing RBC membrane diseases, measures the deformability index (DI)  . Its availability is limited although the invention of new ektacytometers will help widen its use .
Post-splenectomy, patients with HE or HPP exhibit increased hematocrit, decreased reticulocyte counts, and improved clinical symptoms. Patients should be followed for signs of decompensation during acute illnesses. [cancertherapyadvisor.com]
His hemoglobin is now practically normal, but he still has a slight but persistent reticulocyte increase. Cases 2 and 3 were first thought to be due to iron deficiency anemia. [pediatrics.aappublications.org]
Hereditary pyropoikilocytosis (HPP) is a severe, congenital hemolytic anemia occurring almost exclusively in black persons and characterized by extreme red blood cell anisopoikilocytosis. The authors report two unrelated white females with HPP. [ncbi.nlm.nih.gov]
Mean Corpuscular Hemoglobin Concentration Decreased
Hematological values showed an increase in reticulocyte counts and mean corpuscular hemoglobin concentration, decreased mean corpuscular volume and hematocrit, and normal erythrocyte counts that, associated to splenomegaly, indicate that the mice suffer [ncbi.nlm.nih.gov]
Treatment There is no treatment needed for the disorder unless severe anemia or anemia symptoms occur. Surgery to remove the spleen may decrease the rate of red blood cell damage. [stelizabeth.com]
Sensitivity of RBC to heat treatment was studied as well as quantitative changes in proteins by densitometry of 1% SDS--10% PAGE gels. [ncbi.nlm.nih.gov]
Prognosis Prognosis is related to the number of transfusions needed to maintain adequate hemoglobin levels for a growing child and the ability to treat or to prevent life-threatening infections after splenectomy. [emedicine.medscape.com]
Prognosis Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy. [slideshare.net]
(Outcomes/Resolutions) The prognosis of Hereditary Elliptocytosis is good, if the condition is diagnosed early and appropriate treatment provided Uncontrolled Hereditary Elliptocytosis with complications can lead to a poor prognosis Additional and Relevant [dovemed.com]
Comparative studies of the two types of membrane abnormalities in HE clearly showed the absence of correlation between clinical, morphological phenotypes, and specific molecular etiology. [ncbi.nlm.nih.gov]
Her past medical history included normocytic anemia of uncertain etiology, which was treated with iron, during her first pregnancy. At presentation, her physical examination was normal. [bloodjournal.org]
Etiology Hereditary pyropoikilocytosis (HPP) is subtype of hereditary elliptocytosis (HE), a red blood cell (RBC) membrane disorder that results from mutations in the genes encoding α-spectrin ( SPTA1 ), β-spectrin ( SPTB ), or protein 4.1R ( EPB41 ). [emedicine.medscape.com]
(Etiology) Hereditary Elliptocytosis is a congenital genetic disorder that is inherited in an autosomal dominant fashion in a majority of individuals. It is stated to be caused by a deletion in a gene on chromosome 17. [dovemed.com]
Two successive epidemiological investigations revealed fifteen probands in the French Northern Alps. The frequency of this disease seems to be very high in four small villages isolated in the Aravis mountains. [ncbi.nlm.nih.gov]
[…] study, Dissertation, 1984 Berkeley, California University of California pg. 188 Cattani et al., 1986 The epidemiology of malaria in a population surrounding Madang, Papua New Guinea, American Journal of Tropical Medicine and Hygiene, 1986, vol. 35 (pg [doi.org]
HE is caused by monoallelic (heterozygous) mutations and inherited in an autosomal dominant fashion, while HPP has an autosomal recessive inheritance and is typically caused by biallelic (homozygous or compound heterozygous) mutations.  Epidemiology [emedicine.medscape.com]
8790144 ) Pranke P.H....Saad S.T. 1996 41 Molecular basis and haplotyping of the alphaII domain polymorphisms of spectrin: application to the study of hereditary elliptocytosis and pyropoikilocytosis. ( 8755921 ) Gallagher P.G....Forget B.G. 1996 42 Epidemiological [malacards.org]
PMID: 26198474 Nelson MU, Bizzarro MJ, Baltimore RS, Dembry LM, Gallagher PG: Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit in the Decade following Implementation of an Active Detection [medicine.yale.edu]
Nathan and Oski’s is the only comprehensive product on the market that relates pathophysiology in such depth to hematologic and oncologic diseases affecting children. [books.google.com]
Balances summaries of relevant pathophysiology with clear, practical clinical guidance to help you thoroughly understand the underlying science of diseases. [books.google.es]
Pathophysiology Hereditary pyropoikilocytosis (HPP) is a disease emanating from a defect in spectrin, which is the major peripheral protein of the red blood cell (RBC) membrane. [emedicine.medscape.com]
Spherocytic elliptocytosis (hereditary hemolytic ovalocytosis) - the individual is European descent and elliptocytes and spherocytes are simultaneously present in Pathophysiology 2. [slideshare.net]
The father's allele is elliptocytogenic in the heterozygous state and, among other molecular alterations, prevents the attachment of protein 4.1. [ncbi.nlm.nih.gov]
WAS THERE A WAY TO PREVENT IT? This genetic condition is not preventable WHAT ELSE ARE WE WORRIED ABOUT? N/A OTHER HY FACTS? N/A Page Updated: 01.06.2016 [stepwards.com]
This regulatory protein prevents the amplification of C3/C5 convertase activity. D. None of these adequately describes the DAF role. C. This regulatory protein prevents the amplification of C3/C5 convertase activity. 10. [quizlet.com]
The red cells in hereditary elliptocytosis can do this too, but afterwards, their cytoskeletal defects prevent them from reverting to normal biconcave disk form, and they remain stuck in the elliptical shape. [pathologystudent.com]
Currently, there are no specific methods or guidelines to prevent Hereditary Elliptocytosis, since it is a genetic condition. [dovemed.com]
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