eMedicine Specialties > Pediatrics: General Medicine > Hematology

Hemoglobin H Disease: Follow-up

Author: Alexandra C Cheerva, MD, Associate Professor of Pediatrics, Hematology/Oncology Division, Director of Pediatric Blood and Marrow Transplantation, University of Louisville; Attending Staff, Section of Pediatric Hematology and Oncology, Kosair Children's Hospital
Coauthor(s): Ashok B Raj, MD, Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children's Hospital, University of Louisville
Contributor Information and Disclosures

Updated: Jul 16, 2009

Follow-up

Further Outpatient Care

  • Pay close attention to iron overload in patients with hemoglobin H disease (HbH disease).
  • Even patients who have not received a large number of transfusions may have elevated total body iron loads and may require chelation therapy.

Deterrence/Prevention

  • Prenatal testing is available for families at risk (eg, parents are members of ethnic groups with the highest carrier rates). Globin-chain analysis can be performed by means of polymerase chain reaction (PCR) testing.8
  • Although neonatal screening is not sufficient in the diagnosis hemoglobin H disease, patients with the disease at birth have large amounts of hemoglobin Bart (g 4), which is detectable with neonatal screening.

Prognosis

  • The risk of severe anemia and the need for transfusions are lifelong.

Patient Education

  • Educate patients and their parents regarding hemoglobin H disease.
  • Genetic counseling is important for parents of a child with hemoglobin H disease. Parents must understand the risk that future children may have hemoglobin H disease and other, possibly more severe, thalassemia syndromes.

Miscellaneous

Medicolegal Pitfalls

  • Failure to recognize this type of anemia as a genetic condition and to properly inform parents and patients of the potential to have children with hemoglobin H disease (HbH disease) or other thalassemia syndromes
  • Failure to confirm iron deficiency anemia using laboratory testing in a patient with hemoglobin H disease may lead to continuation of supplemental iron therapy for an extended period (usually >3 mo), which may lead to secondary hemachromatosis. If iron overload continues longer than 1-2 years, it can lead to damage in multiple organs, including cardiac, hepatic, and endocrine dysfunction.

Special Concerns

  • Pregnancy: During pregnancy, iron and folic acid deficiencies can alter the mean corpuscular volume (MCV). As a result, thalassemia may be difficult to diagnose or exclude during pregnancy. If a strong suspicion exists and if a definitive answer is required, polymerase chain reaction (PCR) should be performed for globin-chain analysis. Pregnant women with hemoglobin H disease require special care because those women with severe anemia may have serious health problems during their pregnancy and this may adversely affect the health of their fetuses. The incidence of low birth weight is also high in women with hemoglobin H disease and severe anemia.9,10
  • Geriatric patients: A particularly severe acquired form of hemoglobin H disease may occur in elderly men with clonal myeloproliferative diseases. In these patients, hemoglobin H levels may be as high as 60%. Extremely low a -chain– b -chain synthetic ratios may be present, and low a -globin messenger RNA levels are found in bone marrow cells. Hemolytic disease caused by hemoglobin H disease may wax and wane with the course of the myeloproliferative disease.
  • a -thalassemia/mental retardation (ATR) syndromes:
    • In the ATR-16 syndrome, affected children have chromosomal rearrangements involving the short arm of chromosome 16 telomere, which includes the a -globin complex. This results in monosomy for the 16p telomere, and the a -thalassemia phenotype. If an affected child also inherits a single a -globin gene deletion from the other parent, hemoglobin H disease results. These children may also have mental retardation and other congenital anomalies thought to be due to deletions of dose-sensitive genes on chromosome 16p.
    • The ATR-X syndrome is an X-linked disorder caused by mutations of the ATRX gene located on chromosome Xq13.3. It is more frequent than the ATR-16 syndrome. Males who are affected usually have severe intellectual and physical handicaps and other congenital anomalies. Skeletal deformities are present in as many as 90% of patients. The a -thalassemia phenotype varies, with hemoglobin H inclusion bodies found in 0-32% of circulating erythrocytes.
 
Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Afshin Ameri, MD to the development and writing of this article.



More on Hemoglobin H Disease

Overview: Hemoglobin H Disease
Differential Diagnoses & Workup: Hemoglobin H Disease
Treatment & Medication: Hemoglobin H Disease
Follow-up: Hemoglobin H Disease
Multimedia: Hemoglobin H Disease
References
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References

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  15. Leder A, Wiener E, Lee MJ, et al. A normal beta-globin allele as a modifier gene ameliorating the severity of alpha-thalassemia in mice. Proc Natl Acad Sci U S A. May 25 1999;96(11):6291-5. [Medline].

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Further Reading

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Keywords

hemoglobin H disease, alpha-thalassemia syndrome, α-thalassemia syndrome, HbH disease, chronic hemolytic anemia, genetic disorder, thalassemia, anemia, alpha-globin gene, globin protein, malaria protection, alpha-globin chains, jaundice, hepatosplenomegaly, folic acid deficiency, iron deficiency, hydrops fetalis, marrow hyperplasia, bone thinning, maxillary hyperplasia, anemia, treatment, diagnosis

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Contributor Information and Disclosures

Author

Alexandra C Cheerva, MD, Associate Professor of Pediatrics, Hematology/Oncology Division, Director of Pediatric Blood and Marrow Transplantation, University of Louisville; Attending Staff, Section of Pediatric Hematology and Oncology, Kosair Children's Hospital
Alexandra C Cheerva, MD is a member of the following medical societies: American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, International Pediatric Transplant Association, and Kentucky Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Ashok B Raj, MD, Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children's Hospital, University of Louisville
Ashok B Raj, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Kentucky Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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