Edit concept Question Editor Create issue ticket

Hereditary Elliptocytosis


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 [1] [2]. 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 [3] [4] [5]. 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 [3].

There are three morphologic variants of HE: common HE, spherocytic elliptocytosis, and Southeast Asian ovalocytosis, which are all inherited in an autosomal dominant pattern [6] [7]. Note that there is a severe subtype of common HE, known as hereditary pyropoikilocytosis (HPP), which exhibits an autosomal recessive mode of inheritance [6].

While more than 90% of patients with HE are asymptomatic, the clinical presentation is variable depending on the type [1] [8]. 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 [9]. 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.

Physical exam

Individuals with hemolysis may exhibit signs such as pallor, scleral icterus, or splenomegaly. Rarely, patients will develop leg ulcers.

  • 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]
  • Of the two, sickle cell anemia is by far the more common, the incidence being FULL TEXT[doi.org]
  • 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 persist for a long time in a newborn Signs and tests An examination by your health care provider may occasionally show an enlarged spleen .[coordinatedhealth.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]
Failure to Thrive
  • This report emphasises the importance of excluding a renal tubular defect in any child who presents with elliptocytosis and failure to thrive.[ncbi.nlm.nih.gov]
Scleral Icterus
  • Physical exam Individuals with hemolysis may exhibit signs such as pallor, scleral icterus, or splenomegaly. Rarely, patients will develop leg ulcers.[symptoma.com]
Short Arm
  • 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 morphological and biochemical observations suggested that the proband suffers from homozygous hereditary elliptocytosis.[ncbi.nlm.nih.gov]
  • Actin levels were diminished in mutant mice, suggesting alterations in the actin-spectrin junctional complexes due to the absence of adducin. Elliptocytes, ovalocytes, and occasionally spherocytes were found in the blood film of -/- mice.[ncbi.nlm.nih.gov]
  • Blood films on the proband suggested a diagnosis of pyropoikilocytosis.[ncbi.nlm.nih.gov]
  • Several mutations have been identified in a number of individuals on the same genetic background, suggesting a "founder effect."[ncbi.nlm.nih.gov]
  • The differential susceptibility to malaria infection suggested by this study has implications for the evaluation of interventions, including possible future vaccine field trials, in populations where high-frequency ovalocytosis is present.[ncbi.nlm.nih.gov]


The assessment for RBC membrane disorders includes the patient and family history, a full physical exam, and the appropriate investigations.

Diagnostic tests

Key laboratory studies comprise a complete blood count (CBC), reticulocyte count, bilirubin, haptoglobin, lactate dehydrogenase (LDH), Coombs test, potassium, and a peripheral blood smear [10]. 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 [1] [11]. 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 [11]. 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 [11]. 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 [11].

Osmotic gradient ektacytometry, the reference technique for diagnosing RBC membrane diseases, measures the deformability index (DI) [3] [10]. Its availability is limited although the invention of new ektacytometers will help widen its use [3].

Hematocrit Decreased
  • 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]
Reticulocytes Increased
  • 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]
Liver Biopsy
  • Even when her levels of serum bilirubin and transaminases were decreased to the normal ranges and a liver biopsy revealed no evidence of any liver cirrhosis or active hepatitis, ICG excretion still remained abnormal.[ncbi.nlm.nih.gov]


  • Treatment : How to Treat "hereditary elliptocytosis"? The vast majority of those with hereditary elliptocytosis need no treatment whatsoever.[signssymptoms.org]
  • Treatment Return to top There is no treatment needed for the disorder unless red blood cells rupture. Surgery to remove the spleen may decrease red blood cell rupture.[pacificschoolserver.org]
  • 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]
  • Please consult your own licensed physician regarding diagnosis and treatment of any medical condition! Please see also our disclaimer . This site complies with the HONcode standard for health information: verify here . Database updated 2019-03-22.[diseasesdatabase.com]


  • 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]
  • Expectations (prognosis) Most persons with hereditary elliptocytosis have no problems, and are unaware of their condition. Complications Elliptocytosis is frequently harmless. In mild cases, fewer than 15% of red blood cells are elliptical-shaped.[coordinatedhealth.com]
  • Outlook (Prognosis) Most persons with hereditary elliptocytosis have no problems. They often do not know they have the condition. Possible Complications Elliptocytosis is often harmless.[nicklauschildrens.org]


  • 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]


  • 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 ([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. [1] 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]
Sex distribution
Age distribution


  • 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]
  • 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]
  • N/A Pathophysiology The principal defect in HE and HPP erythrocytes is mechanical weakness of the erythrocyte membrane skeleton leading to increased membrane fragility.[cancertherapyadvisor.com]


  • 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]
  • 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]
  • Prevention Genetic counseling may be appropriate for persons with a family history of this disease who wish to become parents.[coordinatedhealth.com]
  • Prevention Genetic counseling may be appropriate for persons with a family history of this disease who wish to become parents. visHeader References Gallagher PG. Hemolytic anemias: red cell membrane and metabolic defects.[nicklauschildrens.org]



  1. Da Costa L, Galimand J, Fenneteau O, Mohandas N. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013; 27(4):167-178.
  2. Soderquist C, Bagg A. Hereditary elliptocytosis. Blood. 2013; 121(16):3066.
  3. Da Costa L, Suner L, Galimand J, et al. Diagnostic tool for red blood cell membrane disorders: Assessment of a new generation ektacytometer. Blood Cells Mol Dis. 2016; 56(1):9-22.
  4. Gallagher PG. Hereditary elliptocytosis: spectrin and protein 4.1R. Semin Hematol. 2004; 41(2):142–164.
  5. Harper SL, Sriswasdi S, Tang HY, et al. The common hereditary elliptocytosis-associated a-spectrin L260P mutation perturbs erythrocyte membranes by stabilizing spectrin in the closed dimer conformation. Blood. 2013;122(17):3045-3053.
  6. Fathima JL, Sitalakshmi S. Cae report on hereditary elliptocytosis. Indian Journal of Medical Case Reports. 2013;2(2):41-43.
  7. Hoffbrand AV, Catovsky D, Tuddenham EGD, Green AR. Hereditary disorders of red cell membrane. In: Postgraduate Haematology. 6th ed. Hoboken, NJ: Wiley-Blackwell; 2011.
  8. Hoffman R, Benz EJ Jr, Shattil SJ, et al. Red cell membrane disorders. In: Hematology Basic Principles and Practice. 3rd ed. London, UK: Churchill Livingstone; 2000: 576-610.
  9. Bayhan T, Ünal Ş, Gümrük F. Hereditary Elliptocytosis with Pyropoikilocytosis. Turkish Journal of Hematology. 2016;33(1):86-87.
  10. King MJ, Garçon L, Hoyer JD, et al. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol. 2015;7(3):304-325.
  11. King MJ, Zanella A. Hereditary red cell membrane disorders and laboratory diagnostic testing. Int J Lab Hematol. 2013;35(3):237-243.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 20:29