Case Studies

An Unexpected Emergency Request for

Glucose-6-Phosphate Dehydrogenase Testing
in a 9-Year-Old African American Boy
Peter Platteborze, PhD,1* Renee Matos, MD,2 Vinod Gidvany-Diaz, MD,2 Kelly Wilhelms, PhD1

Downloaded from https://academic.oup.com/labmed/article/46/2/150/2505057 by guest on 06 April 2023

Lab Med Spring 2015;46:150-152

DOI: 10.1309/LMEEC680QNEHQGIF

CLINICAL HISTORY
Patient: 9-year-old African American male. Previous Medical History: Unknown.

Chief Complaint: Recently diagnosed with acute lymphoblastic
leukemia (ALL) after investigation into a large anterior mediastinal
mass causing airway compression.
History of Present Illness: The day before the unexpected urgent
glucose-6-phosphate dehydrogenase (G6PD) request, the patient was
diagnosed with an aggressive form of leukemia and a significant tumor
mass causing airway compression. A computed tomography (CT) scan
indicated potential renal involvement. Based on this information and the
size of the mass, the patient was referred for immediate chemotherapy.
However, there was a concern that he could develop tumor lysis
syndrome (TLS) during treatment. To avoid this condition, the pediatric
intensive care unit (ICU) sought to pretreat the child with rasburicase,
which led to the emergency G6PD request.
Family History: Largely unknown, but no apparent chronic diseases.
Physical Examination Findings: Three weeks of progressively
worsening lymphadenopathy, coughing, night sweats, mild
hepatosplenomegaly, and breathing difficulty when supine. The
patient arrived at the medical center for airway management and had
a temperature of 36.1°C; blood pressure, 120/87 mmHg; pulse, 115
bpm; respiratory rate, 22 breaths per minute, with labored breathing
but normal O2 saturation while upright and awake, in room air.
Principle Laboratory Findings: Table 1.
Keywords: deficiency, glucose-6-phosphate dehydrogenase,
leukemia, rasburicase, tumor lysis syndrome, uric acid

Questions
1. What are the most striking clinical and laboratory
findings for this patient?

2. Is there a legitimate concern that this patient could

develop tumor lysis syndrome (TLS)?

Abbreviations: 3. What are some treatment options for TLS?

ALL, acute lymphoblastic leukemia; G6PD, glucose-6-phosphate
dehydrogenase; CT, computed tomography; TLS, tumor lysis syndrome; 4. What could occur if this patient were deficient in
ICU, intensive-care unit; UA, uric acid; FDA, United States Food and
glucose-6-phosphate dehydrogenase (G6PD) after
Drug Administration; RBC, red blood cells; NADPH, nicotinamide
adenine dinucleotide phosphate; NA, not applicable; BUN, blood urea receiving rasburicase?
nitrogen.
5. Is it likely this patient has a G6PD deficiency?
Departments of 1Pathology and Area Laboratory Services and
2
Pediatrics, Brooke Army Medical Center, San Antonio, TX
6. What types of laboratory tests are helpful in confirming
*To whom correspondence should be addressed. a diagnosis of G6PD deficiency?

150  Lab Medicine  Spring 2015  |  Volume 46, Number 2 www.labmedicine.com

 Case Studies

Table 1. Laboratory Findings on Admission for

Possible Answers the Patient, a 9-Year-Old African American Boy
Resulting Reference
1. On admission, the patient exhibited several mildly Test Value Interval Units
abnormal laboratory findings, among which were Chemistry
significantly elevated lactate dehydrogenase, uric acid (UA), Albumin 4.2 3.8-5.4 g/dL
and white blood cell count (Table 1). The hyperuricemia of Anion gap 21a 5-14 NA
BUN 14 8-23 mg/dL
the patient prompted the health care providers to administer
Calcium 10.2 8.8-10.8 mg/dL

Downloaded from https://academic.oup.com/labmed/article/46/2/150/2505057 by guest on 06 April 2023

chemotherapy immediately, to address the aggressive Chloride 95a 96-108 mmol/L
leukemia and to restore normal pulmonary function. CO2 18a 22-32 Mmol/L
Creatinine 0.5a 0.7-1.2 mg/dL
2. This patient is at high risk to develop potentially life- G6PD 13.0 7.0-20.5 U/g Hb
threatening TLS, a rare condition that often occurs after Glucose 64a 74-109 mg/dL
Lactate dehydrogenase 1152a 120-300 U/L
chemotherapeutic treatment1,2 of various malignant Phosphorus 3.3 3.0-5.4 mg/dL
neoplasms, especially high-grade lymphomas and Potassium 3.8 3.3-4.5 mmol/L
ALL.3 As its name implies, rapid tumor cell lysis often Sodium 134 133-145 mmol/L
results in elevated levels of UA and significant electrolyte Uric acid 8.6a 3.4-7.0 mg/dL
Hematology
imbalances (ie, potassium, phosphate, and calcium)
White blood cells 21.7a 4.5-13.5 ×103
that can result in crystal deposition in renal tubules and
NA, not applicable; BUN, blood urea nitrogen; G6PD, glucose-6-phosphate
culminate in acute renal failure.1,4 Once chemotherapy dehydrogenase.
a
Abnormal result.
began, we observed shifts in plasma calcium,
phosphorus, and UA levels, consistent with cellular lysis.
product allantoin but also produces hydrogen peroxide,
3. An effective clinical management strategy is to preclude
which can cause severe hemolysis and methemoglobinemia
TLS by concurrently administering intravenous fluids and
in patients with G6PD deficiency.6,7
hypouricemic drugs,5 which increase glomerular flow
and reduce the risk of crystal formation. Historically, the 5. G6PD deficiency is the most common type of enzyme
drug of choice was allopurinol, a competitive inhibitor of deficiency in humans, with an estimated 400 million
xanthine oxidase. In 2002, the United States Food and people affected worldwide. G6PD deficiency is an X-linked
Drug Administration (FDA) approved the use of rasburicase, inherited disorder most commonly affecting persons of
a recombinant urate oxidase that compensates for the African, Southeast Asian, and Mediterranean ethnicity.8,9
inability of the human body to express this enzyme.6 Use of The disease is usually more severe in individuals who
rasburicase in patients yields significantly faster reduction are homozygous for the deficiency. In the United States,
in uricemia and more efficient kidney function than use of African American males are most commonly affected, with
allopurinol in comparable patients.4 In our patient, judicious a prevalence of approximately 10% in that population.10
use of rasburicase resulted in the rapid reduction of UA Because our patient is male and African American, he had
levels and the avoidance of TLS. an increased likelihood of G6PD deficiency.

4. Rasburicase is contraindicated in patients with G6PD
deficiency because administration of this drug could cause
death.6 G6PD catalyzes the first step in the pentose-
phosphate pathway and is critical for red blood cells (RBCs)
to generate the reduced form of nicotinamide adenine
dinucleotide phosphate (NADPH). Individuals with G6PD
deficiency are unable to produce sufficient NADPH to
maintain normal levels of reduced glutathione, making their
RBCs highly susceptible to oxidative damage from certain
drugs, ketoacidosis, infections, and ingestion of fava beans.
Rasburicase reduces UA to the much more water-soluble
6. Appropriate tests to screen for G6PD deficiency involve
assessing the endogenous RBC activity of the patient;
qualitative and quantitative laboratory tests are available for
this purpose. The former test type is much more commonly
used; it is based on an ultraviolet fluorescence spot test.
However, colloquially, these qualitative tests have been
shown to lack sufficient sensitivity to identify many of the
moderate G6PD deficiencies in males or heterozygotic
females. Recently, a 62-year-old African American man with
leukemia was misdiagnosed as not having G6PD deficiency
due to the results of a spot test;6 after being administered

www.labmedicine.com Spring 2015  |  Volume 46, Number 2  Lab Medicine  151

Case Studies

rasburicase, he developed fatal methemoglobinemia. In our

patient, a quantitative assay unequivocally showed that he
did not display G6PD deficiency.

Dedication

We are grateful to have worked with Joseph Andris, BS. To

all who knew him he was a divine inspiration and gallantly

Downloaded from https://academic.oup.com/labmed/article/46/2/150/2505057 by guest on 06 April 2023

remained an optimist until recently succumbing to the
scourge of cancer.  LM

References
1. Davidson MB, Thakkar S, Hix JK, Bhandarkar ND, Wong A,
Schreiber MJ. Pathophysiology, clinical consequences, and
treatment of tumor lysis syndrome. Am J Med. 2004;116:546-554.
2. Cairo MS, Coiffier B, Reiter A, Younes A, TLS Expert Panel.
Recommendations for the evaluation of risk and prophylaxis of
tumour lysis syndrome (TLS) in adults and children with malignant
diseases: an expert TLS panel consensus. B J Haematol.
2010;149:578-586.
3. Wilson FP, Berns JS. Tumor lysis syndrome: new challenges and
recent advances. Adv Chronic Kidney Dis. 2014;21:18-26.
4. Sonbol MB, Yadav H, Vaidya R, Rana V, Witzig TE.
Methemoglobinemia and hemolysis in a patient with G6PD deficiency
treated with rasburicase. Am J Hematol. 2013;88:152-154.
5. Coiffier B, Altman A, Pui CH, Younes A, Cairo MS. Guidelines for
the management of pediatric and adult tumor lysis syndrome: an
evidence-based review. J Clin Oncol. 2008;26:2767-2778.
6. Bucklin MH, Groth CM. Mortality following rasburicase-induced
methemoglobinemia. Ann Pharmacother. 2013;47:1353-1358.
7. Arese P, Gallo V, Pantaleo A, Turrini F. Life and death of glucose-
6-phosphate dehydrogenase (G6PD) deficient erythrocytes–role
of redox stress and band 3 modifications. Tranfus Med Hemother.
2012;39:328-334.
8. Youngster I, Arcavi L, Schechmaster R, et al. Medications and
glucose-6-phosphate dehydrogenase deficiency: an evidence based
review. Drug Saf. 2010;33:713-726.
9. Elyassi AR, Rowshan HH. Perioperative management of the glucose-
6-phosphate dehydrogenase deficient patient: a review of the
literature. Anesth Prog. 2009;56:86-91.
10. Frank JE. Diagnosis and management of G6PD deficiency. Am Fam
Physician. 2005;72:1277-1282.

To read this article online, scan

the QR code, http://labmed.
ascpjournals.org/content/46/2/157.
full.pdf+html

152  Lab Medicine  Spring 2015  |  Volume 46, Number 2 www.labmedicine.com