Patient Presentation
A 3-day-old male came to clinic for a weight and bilirubin checkup. He was feeding well every 2-3 hours for 30 minutes. He was having several stools but they still had meconium. He would awaken but seemed sleeper for the past 24 hours per his mother, and she thought he looked more jaundiced. The past medical history showed that he was a 38 week gestation, appropriate-for-gestation-age, infant born vaginally to a G2P2 O+ female with no risk factors. He had an uneventful post-natal course and was discharged at 48 hours with a total bilirubin of 11.8 mg/dL. His neonatal screening test was normal. The family history was non-contributory other than both parents were originally from Italy and were now living in the United States. The review of systems was negative.
The pertinent physical exam showed a sleepy-appearing male. His weight was 5% down from birth weight and was 2% down since discharge. He was jaundiced to at least his knees but otherwise appeared normal. His transcutaneous bilirubin was 17.2 mg/dL, and a total serum bilirubin was 17.9 mg/dL (high risk). The diagnosis of a healthy appear male with jaundice was made. The patient was admitted to the hospital for phototherapy. During the admission process the mother said that there were people in her family that had G6PD deficiency, but that she did not. The patient’s sibling had jaundice as an infant treated with phototherapy but the parents were not aware that any additional evaluation had been performed. Further laboratory testing showed the patient’s blood smear to have increased hemolysis and an infant blood type of O+ with a negative direct antibody test. His G6PD biochemical assay was positive for the disease. The infant continued under phototherapy for 36 hours. His rebound bilirubin after phototherapy at 5 days of life was 12 mg/dl (low risk). He was seen in the clinic the following day and another bilirubin was 10.8 mg/dL. The family had already been given information about G6PD and agreed to genetic counseling so an appointment had been made.
Discussion
Glucose 6-phosphate dehydrogenase deficiency (G6PD) is an X-linked disease that has multiple mutations. Each mutation causes a different amount of the enzyme to be produced within cells and therefore not all mutations will produce disease. Glucose 6-phosphate dehydrogenase is an enzyme that is critical to the metabolism of all aerobic cells as it catalyzes the rate-limiting step of the pentose phosphate pathway reducing NADP to NADPH. NADPH is important for nucleic acid replication and therefore cell division. G6PD is the only source of NADPH within the cell, so deficiency makes red blood cells susceptible to hemolysis if they are under oxidative stress. Populations at higher risk for G6PD include those who their ethnic heritage is from the Mediterranean, Africa, Middle East and Asia. Newborn screening testing is not routinely done in the United States. Infants are often identified because of the early timing, persistent or extreme levels of hyperbilirubinemia.
Although the levels of hyperbilirubinemia in this patient were not extreme (i.e. > 20 mg/dL), G6PD is a common reason for extreme hyperbilirubinemia. Causes of severe unconjungated hyperbilirubinemia specifically due to problems with red blood cells can be found here. A review of general causes of neonatal unconjugated hyperbilirubinemia can be found here.
Learning Point
Hemolytic episodes in persons with G6PD can be triggered by infections, severe stress, certain foods (such as fava beans), and certain drugs, including:
- Antibiotics – chloramphenicol, cotrimoxazole, nitrofurantoin, quinolones, sulfadiazine
- Antimalarial – dapsone, primaquine, methylene blue, chloroquine, quinine
- Antipyretics – acetaminophen, aspirin, phenazopyridine, sulfasalazine
- Other – Isoniazid, Vitamin C, Vitamin K, rasburicase, thiazide diuretics
- Cardiac – dinitrate, isosorbide
- Hypoglycemics – tolbutamide, glibenclamide
Favism by proxy, that is exposure to fava (broad) beans through breast milk, can also occur.
For health care providers who do not routinely treat patients with this problem, a consultation with a pharmacist or a geneticist may be necessary, particularly if there is a medical need to use a particular drug such as treatment of malaria.
Questions for Further Discussion
1. How common is G6PD worldwide?
2. What would be the pros and cons of universal neonatal screening for G6PD?
Related Cases
- Disease: G6PD Deficiency
- Symptom/Presentation: Jaundice
- Specialty: Genetics | Hematology | Neonatology
- Age: Newborn
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: G6PD Deficiency
To view current news articles on this topic check Google News.
To view images related to this topic check Google Images.
To view videos related to this topic check YouTube Videos.
Christensen RD, Lambert DK, Henry E, Eggert LD, Yaish HM, Reading NS, Prchal JT. Unexplained extreme hyperbilirubinemia among neonates in a multihospital healthcare system.
Blood Cells Mol Dis. 2013 Feb;50(2):105-9.
Watchko JF, Kaplan M, Stark AR, Stevenson DK, Bhutani VK. Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States? J Perinatol. 2013 Jul;33(7):499-504.
Luzzatto L, Seneca E. G6PD deficiency: a classic example of pharmacogenetics with on-going clinical implications. Br J Haematol. 2014 Feb;164(4):469-80.
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
2. Essential and accurate information about the patients’ is gathered.
3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
4. Patient management plans are developed and carried out.
5. Patients and their families are counseled and educated.
7. All medical and invasive procedures considered essential for the area of practice are competently performed.
8. Health care services aimed at preventing health problems or maintaining health are provided.
9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
25. Quality patient care and assisting patients in dealing with system complexities is advocated.
Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital
Pediatric Education 