Significance of beta-thalassemia heterogeneity – hemoglobin H

January 01, 0001

Significance of beta-thalassemia heterogeneity - hemoglobin H

Early diagnosis during newborn screening or infancy has enabled the observation of the natural history of hemoglobin H disease, a subtype of beta-thalassemia. These US authors analyzed longitudinal clinical data for patients with hemoglobin H disease arising from the deletion of three of four alpha-globin genes (HbH) and from hemoglobin H Constant Spring (HCS), caused by the deletion of two alpha-globin genes and the Constant Spring mutation.

They found: "We identified 86 patients with hemoglobin H disease (48 through newborn screening). Of these patients, 60 (70%) had HbH, 23 (27%) had HCS, and 3 (3%) had other, nondeletional forms of hemoglobin H disease. The parental ethnic background was Asian in 81% of patients, Hispanic in 5%, and African American in 3%, whereas mixed ancestry was observed in 10% of patients. Among the patients with deletional hemoglobin H disease, 15% had one or both parents with African-American ancestry. Growth was normal in patients with HbH during the first decade, but growth deficits began during infancy in those with HCS. Anemia was more severe in patients with HCS at all ages. Acute worsening of anemia with infections requiring urgent blood transfusion was observed in patients with HCS but not in those with HbH. The probability of receiving at least one transfusion by the age of 20 years was 3% for patients with HbH and 80% for those with HCS. Among patients with HCS, transfusions occurred in 13% of infants and 50% of children under the age of 6 years; splenectomy was associated with a significant improvement in hemoglobin levels and a reduction in the number of transfusions."

The authors concluded: "HCS should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illnesses. HbH was not associated with an increased rate of severe anemia with infections and was managed without blood transfusions. Many patients with these disorders had mixed ethnic backgrounds, which highlights the need for extended newborn screening in populations that are traditionally considered to be at low risk for hemoglobin H disease."

This begs the question of whether children with HCS should be routinely offered splenectomy.

For the full abstract, click here.

N Engl J Med 364:710-718, 24 February 2011
© 2011 to the Massachusetts Medical Society
Heterogeneity of Hemoglobin H Disease in Childhood. Ashutosh Lal, Michael L. Goldrich, Drucilla A. Haines, Mahin Azimi, Sylvia T. Singer, and Elliott P. Vichinsky. Correspondence to Dr. Lal:

Category: B. Blood/Blood Forming Organs/Immune Mechanisms. Keywords: beta-thallasemia, hemoglobin H, Constant Spring mutation, observational study, journal watch.
Synopsis edited by Dr Linda French, Toledo, Ohio. Posted on Global Family Doctor 15 March 2011

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.