Hemoglobin San Diego: A Case Report and Review of the Literature

BACKGROUND High-oxygen-affinity hemoglobinopathies are rare autosomal dominant disorders caused by missense mutations in globin genes. Such variants decrease oxygen delivery to peripheral tissues, resulting in erythrocytosis. Patients are often asymptomatic, and erythrocytosis is frequently detected incidentally. These hemoglobin variants should be considered in the differential diagnosis, particularly when there is a strong family history of erythrocytosis or when other causes of primary and secondary erythrocytosis have been excluded. Although hemoglobin variants are typically benign, they may be associated with clinical complications. The full spectrum of symptomatology has not yet been elucidated; however, individuals may experience hyperviscosity-related symptoms, including headaches, dizziness, and fatigue. Diagnosis is confirmed through DNA sequencing of globin genes to identify the specific missense mutation. CASE REPORT A 29-year-old otherwise healthy man presented to the hematology clinic for evaluation of persistent erythrocytosis observed over several years, with hemoglobin levels in the 18 g/dL range and hematocrit approximately 51%. Extensive and repeated evaluations for primary and secondary causes of erythrocytosis did not identify a definitive etiology. A rare genetic cause was suspected. Bidirectional sequencing of the beta-globin gene identified a ß109 (GTG→ATG) valine-to-methionine mutation, consistent with the high-oxygen-affinity hemoglobin variant hemoglobin San Diego. CONCLUSIONS Management of high-oxygen-affinity hemoglobin variants remains controversial. Although current guidelines do not recommend routine therapeutic intervention, some evidence suggests that phlebotomy can alleviate symptoms. Additional basic and clinical research is needed to clarify the clinical significance of these variants and establish standardized treatment protocols.