& Ther ics ap tr e a u i t d i c e s P

ISSN: 2161-0665 Pediatrics & Therapeutics Case Report

A 3 Year Old with other Treatments besides Oxygen

Adriana Porto*, Kelly Levasseur Pediatric Emergency Medicine Fellow, Beaumont Hospital, Royal Oak, Michigan, United States

ABSTRACT Background: Glucose-6-phosphatase Dehydrogenase (G6PD) deficiency causes acute hemolysis when exposed to . Methemoglobinemia has been associated with G6PD deficiency, and recognition is important to avoid further complications. Case Presentation: A 3-year-old healthy boy presents to the pediatric emergency department with acute onset of difficulty in breathing, perioral and hypoxia not responding to . Transfusion of packed red blood cells was given with improvement of symptoms. Laboratory results were significant for and methemoglobinemia. Further tests revealed deficiency in glucose-6-phosphatase dehydrogenase . Discussion: G6PD deficiency can cause acute . Cyanosis can be exacerbated by the presence of methemoglobinemia. Management must include transfusion of packed red blood cells and avoidance of to prevent further hemolysis. Conclusion: G6PD deficiency can manifest after exposure to oxidative stressors with acute onset hemolytic anemia and hypoxia. Occasionally methemoglobinemia could be present contributing to worsening symptoms. Keywords: G6PD; Methemoglobinemia; Hypoxia; Pneumonia

INTRODUCTION during an acute hemolysis episode where laboratory report shows elevation of (metHb) levels not known by the patient prior Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X- to the current illness [5]. linked inherited disorder prevalent in people with Mediterranean, African American, Asian and Middle Eastern CASE descent [1]. It is the most common enzyme deficiency and has a variety of manifestations, such as hemolysis and neonatal A previously healthy Middle-Eastern 3-year-old male presented to hyperbilirubinemia. G6PD is found in all cell types and the pediatric emergency department with one day of difficulty produces Nicotinamide Adenine Dinucleotide Phosphate breathing, cough, oral cyanosis and yellow discoloration of the (NADPH) which protects Red Blood Cells (RBC) from oxidative lips. His mother reported fava bean ingestion the night before. damage [2]. G6PD deficiency causes cell destruction when cells On physical exam he was found to be ill appearing, pale and was are exposed to oxidative stressors such as infection, hypoxia, hypoxic with perioral cyanosis. Initial vitals included oxygen certain drugs, or ingestion of fava beans [3]. Favism occurs when saturation 75% on room air, temperature 36.5°C, heart rate a patients with G6PD deficiency ingests fava beans, this is a 118/min, respiratory rate 54/min and blood pressure 119/74. condition that results in acute hemolysis. Patients present with He was placed on oxygen via nasal cannula with improvement of fever, chills, agitation, hypoxia, anemia, and hemoglobinuria. the oxygen saturation to 88%. A CXR was obtained which Occasionally, additional disorders can be found along with showed a right-sided pneumonia. Intravenous (IV) Ceftriaxone G6PD deficiency. Methemoglobinemia is one of those entities was started. Oxygen saturation remained in the high 80’s despite that has been associated with G6PD deficiency [4]. There are supplemental humidified oxygen via nasal cannula at 4L/min. several case reports of patients with elevated levels of Patient was then placed on Continuous Positive Airway Pressure (metHb) also found to have G6PD deficiency (C-PAP) but saturation still remained in the high 80’s. Lab work

*Correspondence to: Adriana Porto, Pediatric Emergency Medicine Fellow, Beaumont Hospital, Royal Oak, Michigan, United States, E-mail: [email protected] Received date: April 18, 2020; Accepted date: May 10, 2020; Published date: June 31, 2020 Citation: Porto A, Levasseur K (2020) A 3 Year Old with Hypoxia other Treatments besides Oxygen. Pediatr Ther 10.362. doi: 10.35248/2161-0665.2020.10.362 Copyright: ©2020 Porto A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Pediatr Ther, Vol.10 Iss.2 No:362 1 Porto A, et al.

revealed the following; capillary blood gas pH 7.32, PCO2 40, minutes of the PRBC transfusion. The patient was admitted to bicarbonate 21 mmol/L, methemoglobin 4.8%, 6.6 the pediatric intensive care unit. G6PD enzyme test resulted low g/dL, and hematocrit 20.2%. A transfusion of Packed Red at 1.3 U/gHgb (normal range 5.7-14.7) confirming the diagnosis Blood Cells (PRBC) was administered over 3 hours. The of G6PD deficiency in addition to methemoglobinemia. The patient’s oxygenation improved dramatically after initiation of patient was discharged home on day 4 after his symptoms had PRBC and oxygen saturation went from 88% to 100% after 40 improved and laboratory values normalized (Table 1).

Table 1: Laboratory trends during admission.

Laboratory Day 0 Day 1 Day 2

Reticulocytes (bil/L) 83 Not done 241

Hemoglobin (gr/dL) 8.1 10.8 11.2

Hematocrit (%) 25.9 31.2 31.5

Red blood cells (tril/L) 2.86 3.65 3.5

Total bilirubin (mg/dL) 3.6 4 2.5

AST (U/L) 53 76 67

ALT (U/L) 16 19 18

BUN (mg/dL) 19 9 8

Creatinine (mg/dL) 0.42 0.36 0.35

AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase; BUN: Blood Urea Nitrogen

DISCUSSION especially if patients have respiratory illness as seen in our patient who had pneumonia and where hypoxia was initially G6PD deficiency is an X-linked inherited condition that can be attributed to this finding. As in any patient in acute respiratory triggered by the ingestion of fava beans resulting in favism. distress, obtaining a blood gas can help in identifying the Patients typically present with hypoxia, respiratory distress, and underlying case of the respiratory distress including acid base laboratory findings of hemolytic anemia. However, cyanosis is disturbances, and elevated levels of methemoglobin. not a common sign unless methemoglobinemia is present [5,6]. Symptoms of methemoglobinemia depend on the percent of In a case series [6] children who visited the emergency methemoglobin in the blood. It has been reported that patients department for either hemolytic anemia or exposure to with methemoglobin levels of greater than 15% typically are medications causing hypoxia without a clear explanation, cyanotic and hypoxic [5]. Our patient’s level was 4.8% which is methemoglobinemia was found in further laboratory studies significantly below the level where patients are expected to be and, some of those patients had undiagnosed G6PD deficiency symptomatic. at the time of presentation. In another case series report [7] methemoglobinemia was also described in a 5 year old patient 2+ Methemoglobin is formed by the oxidation of ferrous (Fe ) iron who ingested a dessert containing nitre powder, revealing that 3+ to the ferric (Fe ) iron in hemoglobin, changing the blood color this entity can develop from other sources besides medications from red to bluish color and will not reverse to red with and genetic predisposition. exposure of oxygen in the setting of methemoglobinemia. In physiologic conditions, the reduction of methemoglobin to Our case describes a pediatric patient with undiagnosed G6PD ferrous hemoglobin is constantly occurring via the CYB5R deficiency who ingested fava beans and also developed enzyme system. There are 2 types of mutations, type I autosomal methemoglobinemia. It was imperative to make this diagnosis recessive is the most common. When this enzyme is deficient, quickly in order to help treat this patient and prevent further methemoglobinemia manifests. Patients with levels exceeding complications. The treatment of methemoglobinemia includes 1.5 g/dL of methemoglobin usually experience signs and administration of methylene blue which activates the NADPH symptoms such as cyanosis and tiredness. reduction pathway. This results in the reduction of methemoglobin to ferrous hemoglobin (Fe2+). In G6PD Although methemoglobinemia is a rare condition in children, deficiency, methylene blue is contraindicated because it can have there are many case reports of patients with a reductant and oxidant effects, exacerbating the acute methemoglobinemia who have low oxygen saturations hemolysis [8,9]. However, or B12 will act by utilizing misinterpreted as true hypoxia [5]. Diagnosis can be delayed an alternative pathway, without worsening hemolysis. Patients

Pediatr Ther, Vol.10 Iss.2 No:362 2 Porto A, et al. with G6PD deficiency and methemoglobinemia instead require 4. Odièvre HM, Danékova N, Mesples B, Chemouny M, Couque N. blood transfusions to replenish the G6PD enzyme and halt the Unsuspected glucose-6-phosphate dehydrogenase deficiency hemolysis. In our patient, blood transfusions were enough to presenting as symptomatic methemoglobinemia with severe significantly improve his clinical status; stopping the hemolysis hemolysis after fava bean ingestion in a 6-year-old boy. Int J Hematol. 2011;93:664-66 and reverting the methemoglobin to hemoglobin [10]. 5. Leunbach LT, Pedersen FJ, Trydal T, Thorgaard P, Helgestad J, Rosthøj S. Acute favism: methemoglobinemia may cause cyanosis CONCLUSION and low readings. Pediatr Hematol Oncol. 2014;31:104-106. Patients presenting with symptoms consistent with hemolytic anemia who have hypoxia not responding to oxygen therapy 6. Friedman N, Scolnik D, McMurray L, Bryan J. Acquired methemoglobinemia presenting to the pediatric emergency need further investigation for methemoglobinemia and G6PD, department: a clinical challenge. CJEM. 2020;1-5. if not already diagnosed. The diagnosis must be made quickly to 7. Ríos PJD, Yong R, Calner P. Code blue: Life-threatening avoid the administration of methylene blue and instead give methemoglobinemia. Clin Pract Cases Emerg Med. 2019;3:95-99. blood transfusion with packed red blood cells. 8. Frank EJ. Diagnosis and Management of G6PD deficiency. Am Fam Physician. 2005;72:1277-282. REFERENCES 9. Rosen JP, Johnson C, McGehee WC, Beutler E. Failure of methylene blue treatment in toxic methemoglobinemia. Frank EJ. Diagnosis and management of G6PD deficiency. AAFP. 1. Association With glucose-6-phosphate dehydrogenase deficiency. 2005;72:1277-1282. Ann Intern Med. 1971;75:83-86. 2. G6PD (glucose-6-phosphate dehydrogenase). Atlas of genetics and 10. Nelson SL, Hoffman SR, Lewin AN, Goldfrank RL, Howland cytogenetics in oncology and haematology. 2017. AM. Methylene blue, goldsfrank’s toxicologic emergencies (9th 3. Rehman A, Shehadeh M, Khirfan D, Jones A. Severe acute edn) McGraw-hill education, New York, United States. 2011. haemolytic anaemia associated with severe methaemoglobinaemia in a G6PD-deficient man. BMJ Case Reports. 2018;2017:223369.

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