Friday, April 24, 2009
Hilton San Diego Bayfront
I. Background: Hemoglobin is a polypeptide tetramer of two α globin chains and two β, γ, or d globin chains, each associated with an oxygen-binding heme group. Genetic mutations in genes coding the globin chains can result in changes in the primary structure of the hemoglobin molecule. This structural change can alter the affinity of the hemoglobin variant to its ligands, resulting in low or high oxygen affinity and unstable heme-globin interactions. II. Objective: We report the clinical and laboratory features associated with a previously undescribed unstable α2 hemoglobin variant in a clinically well child with low peripheral oxygen saturation. III. Design/Methods: Case report IV. Results: The patient was a 2-year-old Caucasian male with persistently low systemic arterial saturation by pulse oximetry and low pO2 on arterial blood gas analysis. He had normal cardiac structure and function by echocardiogram and catheterization. He was otherwise asymptomatic, but the family history was significant for the presence of an abnormal hemoglobin in his mother, maternal uncle, and maternal grandmother. Investigations of this hemoglobin variant included serum concentration, HPLC, isoelectric focusing, globin chain electrophoresis, spectrophotometry, isopropanol and heat stability testing, oxygen dissociation testing, gene sequencing, and x-ray crystallography. Results of these studies identified an alpha globin variant, Hemoglobin Kansas City (α46 Phe →Ser), accounting for 10.5% to 14% of the total hemoglobin, unstable by isopropanol testing, but with normal O2 dissociation curve and P50. V. Conclusions: Hb Kansas City is a newly described unstable alpha globin variant (α46 Phe →Ser) associated with hypoxemia and anemia in the absence of cyanosis and cardiovascular or pulmonary disease. Though oxygen dissociation testing was normal for this variant, the concentration of Hb Kansas City was low and therefore oxygen affinity testing may be unreliable. Also, limitations in purification of the abnormal from wild type hemoglobin may preclude full explanation of the patient's hypoxemia.