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.

• Anemia

  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]

  Nonimmune anemias Hereditary red cell membrane disorders are accounted for by nonimmune hereditary hemolytic anemias caused by defects in membrane proteins located in distinct layers of the red cell membrane. [bredagenetics.com]

  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]

  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]

  Moreover, homozygous HE had been recognized in one of the children born two years previously with a persistent and severe transfusion dependent hemolytic anemia. [ncbi.nlm.nih.gov]

• Fatigue

  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]

• Sepsis

  PMID: 25719574 Bizzarro MJ, Shabanova V, Baltimore RS, Dembry LM, Ehrenkranz RA, Gallagher PG: Neonatal sepsis 2004-2013: the rise and fall of coagulase-negative staphylococci. J Pediatr. 2015 May. [medicine.yale.edu]

• Jaundice

  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]

  A 21-year-old female presented with left epigastric pain and jaundice with numerous elliptical RBCs on blood film. The family history review discovered jaundice in her sibling. [ncbi.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]

  Key Information Appropriate Tests Red cell membrane defect Clinical assessment should include personal and family history of anaemia, neonatal jaundice in particular the need for phototherapy, jaundice and gall stones. [rcpa.edu.au]

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]

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]

Make informed clinical choices for each patient, from diagnosis and treatment selection through post-treatment strategies and management of complications, with new evidence-based criteria throughout. [books.google.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]

(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]

Prognosis Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy. [slideshare.net]

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. [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]

[citation needed] Epidemiology[edit] The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention.[4] Around 90% of those with [en.wikipedia.org]

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]

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test The functional red cell membrane is composed of a cholesterol and phospholipid bilayer anchored by integral proteins to an elastic [mayomedicallaboratories.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]

Malaria can be prevented. When traveling to areas where malaria is found See your doctor for medicines that protect you Wear insect repellent with DEET Cover up Sleep under mosquito netting Centers for Disease Control and Prevention [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]

Currently, there are no specific methods or guidelines to prevent Hereditary Elliptocytosis, since it is a genetic condition. [dovemed.com]

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