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Hereditary Disorders of Red Cell Permeability Clinical Presentation

  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
 
Updated: Feb 19, 2014
 

History

The hereditary stomatocytosis syndromes and allied disorders are usually transmitted in an autosomal dominant pattern, although sporadic cases have been reported. Penetrance varies, with significant disparity in clinical symptoms between affected individuals in the same kindred.

Many patients present with hemolytic anemia in the neonatal period, but others are asymptomatic throughout their lifetime. Aplastic crises associated with parvovirus and other infections have been reported. An unusual characteristic of the stomatocytosis syndromes is a predisposition to severe life-threatening thrombosis after splenectomy.

A number of acquired conditions are associated with stomatocytes in the blood, although these patients do not usually have hematologic symptoms. Stomatocytosis may also be observed with inherited conditions such as Mediterranean stomatocytosis, which does not affect erythrocyte permeability and has an accompanying thrombocytopenia.

Overhydrated hereditary stomatocytosis (OHSt)

The degree of hemolysis and anemia varies. Moderate-to-severe lifelong hemolytic anemia is most typical. A few reports described patients who experienced symptoms of vaso-occlusion, such as dyspnea, chest pain, and abdominal pain, particularly after splenectomy.

Anemia is generally not present at birth, but neonatal jaundice is relatively common and is occasionally serious enough to warrant exchange transfusion. Patients with severe disease are usually younger than 6 months at presentation.

Dehydrated hereditary stomatocytosis (DHSt)

This is the most common form of the hereditary stomatocytosis syndromes. Patients typically present with mild-to-moderate hemolytic anemia. Periodic episodes of jaundice are common. Most patients are asymptomatic, although easy fatigability is a common symptom.

A few case reports have documented DHSt in association with recurrent fetal loss or with hydrops fetalis. The presence of perinatal effusions may require ascitic taps but is not a predictor of the severity of anemia later in life.[16] The mechanism for this is uncertain but may involve hepatic dysfunction.[17]

Iron overload is common, and adults may be diagnosed with hemochromatosis. The mechanism for this is unknown.[18]

Intermediate syndromes

Patients with intermediate syndromes do not have consistent hemolytic anemia.

Cryohydrocytosis (CHC) is an intermediate syndrome in which erythrocytes undergo spontaneous in vitro hemolysis after storage at 4°C.

Familial pseudohyperkalemia (FP) manifests with factitious hyperkalemia. Red cell macrocytosis is rare.

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Physical

Focus the physical examination on organ systems affected by hemolytic anemia. Pallor, jaundice, hepatosplenomegaly, and signs of gallstone disease are the most likely physical findings. Evaluate signs of cardiovascular compromise in patients who are ill. Monitor growth parameters yearly in children. Monitor ferritin levels for iron overload.

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Causes

As described above, the hereditary stomatocytosis disorders and allied syndromes are all inherited in an autosomal dominant fashion. Dehydrated hereditary stomatocytosis and some cases of FP map to chromosome band 16q23-24. CHC is associated with mutations of band 3 (AE1). Overhydrated hereditary stomatocytosis has been associated with mutations of RHAG.

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Contributor Information and Disclosures
Author

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP Professor of Pediatrics, Albany Medical College; Chief, Division of Pediatric Hematology-Oncology, John and Anna Landis Endowed Chair for Pediatric Hematology-Oncology, Medical Director, Melodies Center for Childhood Cancer and Blood Disorders, Albany Medical Center

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, International Society of Pediatric Oncology

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.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, 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

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Hematology/Oncology, The Children's Hospital at Memorial University Medical Center; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, International Society of Paediatric Oncology

Disclosure: Nothing to disclose.

References
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  3. Bruce LJ, Robinson HC, Guizouarn H, et al. Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1. Nat Genet. 2005 Nov. 37(11):1258-63. [Medline].

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  16. Grootenboer-Mignot S, Cretien A, Laurendeau I, et al. Sub-lethal hydrops as a manifestation of dehydrated hereditary stomatocytosis in two consecutive pregnancies. Prenat Diagn. 2003 May. 23(5):380-4. [Medline].

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Hereditary stomatocytosis. 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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