Kimberly P. Dunsmore, M.D.
University of Virginia Children's Medical Center
Charlottesville, VA

Introduction

G6PD deficiency is one of the more common RBC enzyme deficiencies with incidence rates in Black males in the United States estimated at 11%. It is inherited in an x-linked recessive manner. Most children with G6PD deficiency are hematologically normal unless they undergo oxidative stress. Many pediatric patients are not diagnosed until they have an acute hemolytic crisis. In the midst of the acute crisis, it can be difficult to make the diagnosis of G6PD deficiency due to the increased amount of G6PD in reticulocytes and young red blood cells. Oxidative stressors can be infectious agents, drugs, chemicals and certain legumes. In G6PD deficient patients, oxidative stress exposes interior sulfhydryl groups that are oxidized and cannot be reduced, leading to irreversible denaturation of the hemoglobin with Heinz body formation. The same agents which lead to hemolysis in G-6PD deficiency can also lead to the formation of methemoglobin. The following case report illustrates the clinical severity that can occur when potent oxidizers induce methemoglobinemia and hemolysis in G6PD-deficient patients.

Case Report

A three-year-old Black male was admitted to the pediatric intensive care unit at the University of Virginia with anemia, hematuria and methemoglobinemia. He had been in his usual state of good health until 2 days prior to admission when he developed non-bloody diarrhea and emesis. Shortly thereafter, his mother noticed his urine to be tea colored. He was seen by his local physician the next day who made a presumptive diagnosis of UTI and placed the child on amoxicillin. Over the next few hours, the child became more irritable and complained of abdominal pain. He developed incontinence of bowel and bladder. He was seen in his local ER, admitted with presumed severe UTI and treated with ceftriaxone. CBC revealed a white blood cell count of 29.6 x 109/L, hemoglobin of 8gm/dL and platelet count of 249 x 109/L. A Coomb's test was negative. G6PD assay was normal. Urinalysis revealed 10-15 WBC per high power field, RBC too numerous to count, positive protein and bilirubin. He had a normal renal ultrasound. Urine culture obtained on admission was subsequently negative. During the next several hours, the patient became more lethargic and was noted to have room air oxygen saturations of 78% without obvious respiratory distress. Methemoglobin was noted to be 21.6%. The patient was transferred to the University of Virginia. On arrival, the patient was non-responsive and pale. He was icteric, tachycardic with good pulses and had moderate enlargement of his liver and spleen. His urine and arterial blood were brown. Oxygen saturations were in the 60's. Admission hemoglobin was 4.5gm/dL, white blood cell count 22.3 x 109/L and platelet count 271 x 109/L. The smear revealed numerous schistocytes, hemighost cells and polychromasia. Bilirubin was 5.1mg/dL, LDH 6714U/L, AST 156U/L, ALT 12U/L, creatinine 0.6mg/dL and urinalysis showed large blood and protein with greater than 50 RBC per high power field. A coagulation profile was normal. Urine and stool cultures were negative. The patient received 1mg/kg of methylene blue with rapid improvement in his oxygenation and then a RBC transfusion. His clinical status was dramatically improved over the next several hours.

Further discussion with his mother revealed that she had found him playing in her laundry detergent the day before his symptoms started. His past medical history was also pertinent for significant neonatal jaundice with a peak bilirubin of 20.3mg/dL. He had a work-up for hepatic causes of hyperbilirubinemia. A cholangiogram at that time revealed poor uptake in the biliary system, but intraoperative cholangiogram revealed uptake with a mildly narrowed biliary duct system. His liver biopsy was normal. He did not have a work-up for hemolytic causes of neonatal jaundice. After recovery from his acute hemolytic crisis, a repeat G6PD assay was done which revealed deficiency. The patient has fully recovered with normal hematologic and renal parameters.

Conclusion

Potent oxidants which induce methemoglobinemia can cause severe clinical symptoms in patients with G6PD deficiency. Detergents are strong oxidants, and appears to be the inciting agent in this patient's crisis. Gastroenteritis from E. coli or other bacterial infection was also investigated as the etiology, but no urine or stool culture ever grew a pathogen. This case illustrates a severe clinical picture of acute hemolytic crisis with methemoglobinemia in a patient with G6PD deficiency. It also points out that diagnosis can be difficult in the acute phase, and when clinical suspicion is high for G6PD deficiency, repeat testing should be done when the patient has recovered from the acute hemolysis.