Hb Manukau [β67(E11)Val → Gly; HBB: c.203T>G]: The Role of Genetic Testing in the Diagnosis of Idiopathic Hemolytic Anemia

Abstract

The increasing availability of DNA sequencing of globin genes has improved our ability to detect conditions that were presumed to be extremely rare. These conditions may remain undiagnosed due to unfamiliarity with clinical presentation, relative unavailability of advanced diagnostic alternatives, or may defy detection by being electrophoretically silent or extreme instability rendering their presence to be below detection level. Genetic studies were pursued in a mother and daughter with severe hemolytic anemia as initial testing failed to be diagnostic. DNA sequence analysis of the β-globin gene identified Hb Manukau [β67(E11)Val → Gly; HBB: c.203T > G], an extremely unstable hemoglobin (Hb) variant. This is the second family described with this condition (first in the western hemisphere). An astute clinician may benefit from being persistent and pursuing additional testing including molecular genetic characterization where clinical suspicion remains high.

• Genetic testing
• Hb Manukau
• hemoglobinopathy
• unstable hemoglobin (Hb)

Acknowledgments

We thank David H. K. Chui, M.D., Director, Hemoglobin Diagnostic Reference Laboratory, Boston University, Boston, MA, USA and Ian Browoski, M.D., Tampa General Hospital, Tampa, FL, USA for their help with the work-up of this family.