Hb H disease: clinical course and disease modifiers.

Abstract

Hemoglobin H (Hb H) disease is the most common form of thalassemia intermedia and has many features that require careful consideration in management. In the majority of cases, Hb H disease results from double heterozygosity for alpha(0)-thalassemia due to deletions that remove both linked alpha-globin genes on chromosome 16, and deletional alpha(+)-thalassemia from single alpha-globin gene deletions (--/-alpha). However, Hb H disease may occur from interactions between alpha(0)-thalassemia with non-deletional mutations (alpha(T)alpha or alpha(T)) or with abnormal hemoglobins such as Hb Constant Spring, Hb Paksé, Hb Quong Sze, and Hb Pak Num Po. In a steady state, patients with Hb H diseases have hemoglobin levels around 9 to 10 g/dL; however, during hemolytic crisis, which frequently develops in or after acute infections with high fever, the hemoglobin level may drop significantly and patients can develop shock or renal shutdown. Even though splenectomy leads to significant elevation of hemoglobin levels, it is not recommended because the majority of patients do well with said steady-state hemoglobin levels. Patients with non-deletional Hb H disease are usually more anemic with significant splenomegaly, and some may require regular blood transfusions and be even as severe as "Hb H hydrops fetalis." However, there is no clear genotype-phenotype correlation associated with this severe clinical syndrome since patients with identical genotypes do not necessary show the same severity. This suggests that other genetic and environmental factors play a role in modifying the degree of clinical severity in patients with non-deletional Hb H disease.