A61-10 Look Beyond the Lungs: A Rare Cause of Dissociated Oxygen Saturation in a Pediatric Patient

Introduction Low oxygen saturation (SpO2) in a clinically well child without cyanosis or respiratory distress typically triggers evaluation for the classic causes of hypoxemia: hypoventilation, V/Q mismatch, shunt, diffusion limitation, and low FiO2. When such a workup is unrevealing, clinicians must consider mechanisms of Dissociated Oxygen Saturation, a state where oxygen delivery is impaired due to abnormal hemoglobin rather than defective gas exchange. Structural hemoglobin variants with altered oxygen affinity represent a rare but critical diagnostic consideration for this phenomenon. Case Report A full-term 6-month-old male with mild eczema presented with apparent low oxygen saturations (83-85%) on room air following a mild viral illness. He appeared well with brisk capillary refill, no cyanosis, and no respiratory distress. His low SpO2 was discordant with his clinical state. Chest radiograph and echocardiogram with bubble study were normal. Methemoglobin was low (1.3%). Family history revealed a maternal history of low SpO2 at baseline. An arterial blood gas (ABG) revealed a PaO2 > 170 mmHg on room air, confirming the absence of true hypoxemia. Hemoglobin electrophoresis showed a minor unidentified peak, prompting molecular testing, which confirmed heterozygous Hemoglobin Abington (HBB: c.211G>C, p.A71P), a rare unstable β-globin variant with decreased oxygen affinity. Variant quantification was approximately 38%. At a two-months follow-up visit, he was thriving, required no transfusions and was started on folic acid, with counseling to avoid oxidative stressors, recommended by Hematology. Discussion This case highlights a rare cause of discordant oxygen measurements resulting from a low-affinity hemoglobin variant that causes a low SpO2 despite normal oxygen tension (PaO2). The key diagnostic clue was the mismatch between low SpO2 and a high arterial PaO2 > 170 mmHg, which definitively ruled out true hypoxemia due to pulmonary or cardiac pathology. The low-affinity Hb Abington causes the hemoglobin to unload oxygen more readily, resulting in a true but low SpO2 measured despite effective alveolar-arterial gas exchange (normal PaO2). This classification answers the diagnostic question when there is an unrevealing cardiopulmonary investigation, and reinforces the importance of integrating clinical appearance and molecular diagnostics when oxygen saturation readings do not align. More than 1,500 structural hemoglobin variants have been described, many undetectable by standard electrophoresis. Recognition of this physiologic mismatch can help to prevent extensive cardiopulmonary investigations and anxiety for families. For trainees, this case reinforces the importance of integrating clinical appearance, family history, and molecular diagnostics when oxygen saturation and clinical findings do not align.