Haemoglobin H ( HbH ) disease

Haemoglobin H is a beta-4 tetramer which occurs when there are excess beta chains produced in the presence of defective alpha chain synthesis (1). This disease results from the inheritance from one parent of alpha0 thalassaemia and from the other alpha+ thalassaemia (1).

Thus these patients have the genotype --/-alpha and are functioning on one rather than four alpha globin genes. They are moderately anaemic (Hb 8-10g/dl) with splenomegaly and have haemoglobin H in their red cells (1). Some develop fatal hydrops fetalis syndrome in utero (1).

Patient's haemoglobin in this condition is composed of:

• HbH (beta4) 5 - 40% (1)
• HbA (alpha2, beta2) 57%
• HbA2 (alpha2, delta2) 1-2% (1)

Haemoglobin H has a high oxygen affinity and is also unstable and precipitates in the circulation giving rise to intracellular inclusions which damage the red cells in their passage through the microvasculature (1).

There is some evidence that pyrexia can increase the formation of Hb H which may account for the acute hemolytic crisis and drop in hemoglobin associated with infections in some (1).
Patients also have evidence of iron overload with elevated serum ferritin levels (1).

Treatment is supportive

• folic acid supplement
• avoidance of oxidative compounds and medications
• prompt treatment of infections
• in adults vigilance for iron overload.
• blood transfusion (usually only reserved for haemolytic crisis, e.g. infections, pyrexia, oxidative challenge, aregenerative anemia, hypersplenism, or during pregnancy, but occasionally regular transfusions maybe required.)
• splenectomy - for people with marked splenomegaly and hypersplenism (1).

Longevity is unaffected.

Reference:

• (1) David H. K. Chui, Suthat Fucharoen, and Vivian Chan, S, 2003. Hemoglobin H disease: not necessarily a benign disorder. Blood, 101 (3), 791-800