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Pediatric Hereditary Elliptocytosis and Related Disorders Clinical Presentation

  • Author: Trisha Simone Tavares, MD, FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Oct 16, 2013
 

History

The clinical presentation of hereditary elliptocytosis widely varies. Most patients are asymptomatic, and the diagnosis is usually made incidentally when a blood smear is examined. Asymptomatic patients are heterozygous for the condition and are classified as having mild or common hereditary elliptocytosis.

Approximately 10% of patients have moderate-to-severe anemia, with intermittent episodes of acute hemolysis with jaundice and splenomegaly. Patients with severe hereditary elliptocytosis or with hereditary pyropoikilocytosis are almost always homozygotes or compound heterozygotes. These patients are often transfusion dependent. Differences in clinical severity reflect manifestations of different mutations and are closely related to the extent of membrane surface area loss.[6]

All patients with conditions predisposing them hemolytic anemia are expected to be at risk of aplastic crisis during infection with parvovirus B-19.

Common or mild hereditary elliptocytosis

In neonates with common hereditary elliptocytosis, a precise diagnosis often cannot be established. The classic morphological findings may not be present.

Common hereditary elliptocytosis is rarely symptomatic in the neonatal period. Severe hemolytic anemia with poikilocytosis and jaundice may occasionally occur. Blood smear evaluation may reveal pyknocytes instead of elliptocytes. Pyknocytes are irregular, dense, distorted, spiculated RBCs similar to acanthocytes. Typically, elliptocytes do not appear in the blood until several months after birth.

Red blood cell survival is shorter than 120 days in neonates, particularly in premature neonates, so anemia may be severe. Anemia may be absent, however, if a persistent increase in reticulocyte production is able to compensate for hemolysis.[7]

Even when neonatal hemolysis is severe, this typically resolves by the time the patient is aged 12 months, and the anemia gradually improves.

Some neonates who present with moderate hemolysis and blood smear findings consistent with hereditary pyropoikilocytosis may have a course that gradually evolves into mild anemia with little or no hemolysis.

In children and adults, common hereditary elliptocytosis is usually asymptomatic or associated with mild sporadic hemolytic anemia.

The degree of hemolysis does not correlate with the percentage of elliptocytes seen in the blood.

The severity of hemolysis in common hereditary elliptocytosis varies not only among different kindreds but also within given families.

Spherocytic elliptocytosis

Spherocytic hereditary elliptocytosis is rare. The exact prevalence is unknown. Most patients have mild or moderate hemolysis. Blood smears show spherocytes, microspherocytes, and microelliptocytes. The elliptocyte percentage may be low.

Severe hereditary elliptocytosis and hereditary pyropoikilocytosis

Often, patients with homozygous hereditary elliptocytosis or hereditary pyropoikilocytosis have symptomatic hemolytic anemia that requires transfusion support and eventual splenectomy.

Many patients with hereditary pyropoikilocytosis present in the early newborn period with severe hemolytic anemia. Blood smears reveal RBC fragmentation, poikilocytosis, elliptocytosis, and microspherocytosis.

Neonatal hyperbilirubinemia and severe anemia in the first few months of life are typical.

Complications of severe anemia, including splenomegaly, growth retardation, frontal bossing, and early gallbladder disease, are common.

Southeast Asian ovalocytosis

Southeast Asian ovalocytosis is a mild form of elliptocytosis. Although this is a considered a benign disorder, neonates may experience hemolysis. The RBC membrane is rigid and hyperstable. Stomatocytes are RBCs with broad oval shapes and one or more stoma in a variety of orientations.[4] Hemolysis is minimal or absent outside of the newborn period.

Southeast Asian ovalocytosis confers some protection against Plasmodium falciparum and Plasmodium vivax infection. Individuals with Southeast Asian ovalocytosis have a significant reduction in the frequency and severity of cerebral malaria.[8]

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Physical

Most patients have normal physical examination findings. Patients undergoing hemolysis may have signs of cardiovascular compromise, pallor, jaundice, and/or acute splenomegaly. Patients with severe forms may exhibit signs of chronic anemia, such as frontal bossing, failure to thrive, and chronic splenomegaly.

Adults may have skin ulcers.[9]

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Causes

Hereditary elliptocytoses are inherited disorders. Some patients with bone marrow dysfunction have developed acquired hereditary elliptocytosis.[2]

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Contributor Information and Disclosures
Author

Trisha Simone Tavares, MD, FAAP Attending Physician, Department of Pediatrics, Section of Hematology/Oncology, Cardon Children's Medical Center

Trisha Simone Tavares, MD, FAAP is a member of the following medical societies: Children's Oncology Group

Disclosure: Nothing to disclose.

Coauthor(s)

Richard H Sills, MD Professor of Pediatrics, Upstate Medical University

Richard H Sills, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gary D Crouch, MD Associate Professor, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research

Disclosure: Nothing to disclose.

References
  1. Grace RF, Lux SE. Disorders of the Red Cell Membrane. Orkin SH, ed. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia, Pa: Saunders Elsevier; 2009. Chapter 15.

  2. Knight J, Czuchlewski DR. Acquired elliptocytosis of myelodysplastic syndrome. Blood. 2013 Jan 24. 121(4):572. [Medline].

  3. Barcellini W, Bianchi P, Fermo E, et al. Hereditary red cell membrane defects: diagnostic and clinical aspects. Blood Transfus. 2011 Jul. 9(3):274-7. [Medline]. [Full Text].

  4. Garnett C, Bain BJ. South-East Asian ovalocytosis. Am J Hematol. 2013 Apr. 88(4):328. [Medline].

  5. Soderquist C, Bagg A. Hereditary elliptocytosis. Blood. 2013 Apr 18. 121(16):3066. [Medline].

  6. Da Costa L, Galimand J, Fenneteau O, Mohandas N. Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. Blood Rev. 2013 May 9. [Medline].

  7. Brugnara C, Platt OS. The Neonatal Erythrocyte and Its Disorders. Orkin SH, ed. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia, Pa: Saunders Elsevier; 2009.

  8. Rosanas-Urgell A, Lin E, Manning L, Rarau P, Laman M, Senn N. Reduced risk of Plasmodium vivax malaria in Papua New Guinean children with Southeast Asian ovalocytosis in two cohorts and a case-control study. PLoS Med. 2012. 9(9):e1001305. [Medline].

  9. Heeney M, Dover GJ. Orkin SH, ed. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia, Pa: Saunders Elsevier; 2009. Chapter 19.

  10. Luzzatoo L, Poggi V. Glucose-6-Phosphate Dehydrogenase Deficiency. Orkin SH, ed. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia, Pa: Saunders Elsevier; 2009. Chapter 17.

  11. Ipsaro JJ, Harper SL, Messick TE, Marmorstein R, Mondragon A, Speicher DW. Crystal structure and functional interpretation of the erythrocyte spectrin tetramerization domain complex. Blood. 2010 Jun 10. 115(23):4843-52. [Medline]. [Full Text].

  12. Wilder JA, Stone JA, Preston EG, Finn LE, Ratcliffe HL, Sudoyo H. Molecular population genetics of SLC4A1 and Southeast Asian ovalocytosis. J Hum Genet. 2009 Mar. 54(3):182-7. [Medline].

  13. King MJ, Bruce LJ, Dhermy D. Hemolytic Anemias Associated with Disorders of Erythrocyte Membrane and Cytoskeleton Proteins. Kottke-Marchant K, Davis BH, eds. Laboratory Hematology Practice. Oxford, UK: Wiley-Blackwell; 2012.

  14. Caprari P, Tarzia A, Mojoli G, Cianciulli P, Mannella E, Martorana MC. Hereditary spherocytosis and elliptocytosis associated with prosthetic heart valve replacement: rheological study of erythrocyte modifications. Int J Hematol. 2009 Apr. 89(3):285-93. [Medline].

 
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Cigar-shaped erythrocytes seen in hereditary elliptocytosis. Courtesy of Jean A. Shafer, BS, MA, Assistant Professor of Hematology and Pathology at the University of Rochester School of Medicine and Dentistry.
Schematic diagram of the components of the RBC membrane. Hereditary elliptocytosis can result from defects of alpha or beta spectrin or from a defective spectrin-actin-protein 4.1R junctional complex.
Bizarre RBC morphology seen in hereditary pyropoikilocytosis. Courtesy of Jean A. Shafer, BS, MA, Assistant Professor of Hematology and Pathology at the University of Rochester School of Medicine and Dentistry.
 
 
 
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