Acyanotic Hypoxia in a Febrile Child Fiona Murphy, MBChB,* Julian Blackham, MBChB, DIPFRCA, DIMC, MRCEM,* John Moppett, MA, MB, BChir, MRCP, FRCPath, PhD,† and Mark Lyttle, MBChB, RCPCH, CSAC, PEM† Abstract: Glucose-6-phosphate dehydrogenase deficiency affects ap- proximately 400 million people worldwide and is an X-linked disorder most commonly found in individuals of African, Asian, Mediterranean, and Middle Eastern descent. It can present with acute hemolysis in re- sponse to certain drugs, infections, or fava beans, and affected individuals may not be aware that they have glucose-6-phosphate dehydrogenase defi- ciency. This case illustrates the importance of those working in the acute and urgent care sector having an awareness of the condition and the value of a full set of vital signs in an unwell child. Key Words: glucose-6-phosphate dehydrogenase deficiency, hemolysis, methemoglobinemia, pulse oximetry (Pediatr Emer Care 2017;00: 00–00) CASE A previously healthy 4-year-old boy was brought to the emergency department by his Iranian parents, having been unwell for 24 hours with a pyrexial illness associated with vomiting, leth- argy, and headache. His parents reported that he was more pale than normal and his skin appeared to have a yellow tinge. On examination, he was pale and slightly jaundiced. Despite a pyrexia of 39°C, most of his observation results were entirely normal. However, his oxygen saturations measured using pulse oximetry were 81% in air. Despite this finding, there was no evi- dence of respiratory or cardiac disease on examination. There was no cyanosis or respiratory distress, and no tachypnea or tachy- cardia. Multiple pulse oximetry devices were used to confirm this reading, and administration of high-flow oxygen increased his measured oxygen saturation only to 85%. On further questioning, there were no previous similar epi- sodes. He had not been overseas recently, and the possibility of toxin ingestion was excluded. His parents revealed he had eaten fava beans a few days before presentation, but he had eaten these before with no apparent adverse effects; this information was volunteered because they were aware of a relative who had been advised not to eat fava beans. A venous blood gas was performed, which showed a hemoglobin level of 7.4 g/dL and a methemoglo- bin level of 6.1%. Laboratory investigations showed a blood picture consistent with intravascular hemolysis secondary to glucose-6-phosphate de- hydrogenase (G6PD) deficiency, and his G6PD level was 1.4 IU/g of hemoglobin (reference range, 4.6–13.5 IU/g). He was treated with a blood transfusion yielding rapid improvement in his labo- ratory and clinical parameters. No causative pathogen was identi- fied for his pyrexial illness, and he made a full recovery. He was diagnosed as having G6PD deficiency and secondary acquired methemoglobinemia, with further familial screening to be com- pleted in the outpatient setting. DISCUSSION This case highlights the importance of physicians being aware of population-specific conditions given constantly evolving ethnography secondary to international migration. A deficiency of G6PD is particularly relevant because it is the most common en- zyme deficiency worldwide 1 and may only present when precipi- tated by certain stressors in previously asymptomatic individuals who do not know that they have the disorder. It also has important implications for the future of these individuals for preventing further crises. A deficiency of G6PD deficiency is an X-linked disorder that is common in Africa, Asia, the Mediterranean, and the Middle East. 1 It is the most common enzyme deficiency worldwide, with more than 300 known variants. 2 Glucose-6-phosphate dehydroge- nase is an enzyme in the pentose monophosphate pathway that prevents oxidative damage to cells by free radicals by producing reduced glutathione. 3 Erythrocytes are particularly vulnerable be- cause this pathway is their only source of reduced glutathione; as oxygen carriers, they are vulnerable to free radical damage. 3 In af- fected individuals, exposure to oxidative stressors can result in acute hemolysis. 2–4 The mainstay of care in G6PD deficiency is prevention of crises through avoidance of oxidative stressors where possible, which include infection, drugs, and some dietary constituents. 1 Examples of drugs that can cause hemolysis in some individuals with G6PD deficiency include the antimalarial primaquine, nitrofurantoin, glibenclamide, and methylene blue. 5 The most well known dietary trigger is the ingestion of fava beans (Vicia fava), 1 which are commonly known in some countries as broad beans. Although this child had ingested fava beans previ- ously without ill effects, it may be that on this occasion, the febrile illness triggered a clinically significant hemolysis. It is recognized that fava bean ingestion alone does not always result in hemolytic crises in some individuals with G6PD deficiency and that infec- tion alone can be a trigger. 5 Methemoglobin is a dyshemoglobin wherein ferrous iron Fe 2+ (essential for adequate tissue oxygen delivery) is in the oxidized state of ferric iron Fe 3+ . This results in left shift of the oxygen- hemoglobin dissociation curve with impaired delivery of oxygen to tissues. 6,7 In the normal state, hemoglobin is continually being oxidized, but 2 enzyme systems function to maintain methemo- globin levels lower than 2%. 8 Methemoglobinemia can therefore result from excessive oxidization of hemoglobin, or a decrease in the activity of reducing enzymes. One of these enzyme systems is the G6PD/glutathione pathway; in the context of G6PD defi- ciency, it can be overwhelmed by oxidative stressors resulting in raised methemoglobin levels. Symptoms reflect tissue hypoxia and increase in severity as the proportion rises, ranging from headache and dyspnea to seizures and coma. 8 Methemoglobinemia, as in this case, makes pulse oximetry unreliable. 7,9,10 Pulse oximetry compares the relative light absorp- tion of blood at 2 wavelengths: reduced hemoglobin has a peak ab- sorption at 660 nm and oxyhemoglobin has a peak absorption at 940 nm. 11 Methemoglobin absorbs light equally at both of these From the *Emergency Department, North Bristol NHS Trust, Southmead Hos- pital; and †Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK. Disclosure: The authors declare no conflict of interest. Reprints: Fiona Murphy, MBChB, Emergency Department, North Bristol NHS Trust, Southmead Hospital, Gate 35 Brunel Bldg, Southmead Rd, Bristol, BS10 5NB, UK (e‐mail: Fiona.murphy@nbt.nhs.uk). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0749-5161 ILLUSTRATIVE CASE Pediatric Emergency Care • Volume 00, Number 00, Month 2017 www.pec-online.com 1 Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.