A Case for Co-oximetry: Methemoglobinemia secondary to a Rare Hemoglobin Variant

Abstract Introduction/Objective The presence of dyshemoglobins and some inherited hemoglobin (Hb) variants can cause over or underestimation of oxygen saturation (O2sat) when using a pulse oximeter (ox). These noninvasive medical devices rely on two wavelengths, a pulsing arterial bed, and light absorption properties of Hb to measure the difference between deoxy- and oxy-Hb. In contrast, a co-oximeter (co-ox) requires arterial blood. By using at least four wavelengths, co-ox measures the functional and fractional O2sat to detect all forms of Hb, including those that do not bind oxygen (O2), such as methemoglobin (metHb). Methemoglobinemia may be congenital or acquired, resulting from exposure to certain toxins, metabolic disorders, enzymatic deficiencies such as cytochrome b5 reductase deficiency, or hemoglobinopathies. Methods/Case Report A healthy, adolescent male undergoing a sports physical at his pediatrician’s office was hypoxic by pulse ox and sent to the emergency department (ED) for evaluation. On exam, he had cold, blue tinged fingertips and lips but was otherwise asymptomatic. His O2sat was 88-90% on room air with minimal improvement with 6L of supplemental O2. Co-ox revealed a metHb level > 20%. The father also mentioned that the mother had frequent ED visits for hypoxia. Capillary Hb electrophoresis showed peaks in the HbA, HbF, and HbA2 zones of 78.3%, 17.9%, and 3.6%, respectively. All CBC parameters were within the reference intervals. The large peak in the HbF zone would suggest hereditary persistence of fetal hemoglobin (HPFH); however, the clinical picture was not consistent. Further reference laboratory investigation determined that the patient was heterozygous for Hb Tübingen (HbTüb), a beta globin chain variant resulting from a point mutation at position 106. By mass spectrometry, the variant quantified as 38% of the total hemoglobin, indicating underestimation by electrophoretic techniques. Results (if a Case Study enter NA) NA Conclusion This case presents an essentially asymptomatic patient with hypoxia and elevated methemoglobin levels. Electrophoretic hemoglobinopathy and CBC workup were clinically inconsistent with HPFH and the presence of an aberrant hemoglobin migrating in the HbF must be considered in the differential diagnosis. The manifestation of HbTüb as methemoglobinemia in this context adds complexity to the diagnostic puzzle. Further laboratory exploration into the underlying mechanisms driving this unique presentation is crucial for a comprehensive understanding and tailored management approach.