You have noticed that a 27-year-old male intern in your residency class seems to have a yellowish color to his skin and eyes in the mornings after being on-call.
The yellow color seems to be worse when he had little sleep.
The yellow color does not seem to be there on non-call mornings. After a couple weeks of noticing this, you finally are convinced that this pattern is real and decide to privately talk to him about it.
He says that he has Gilbert’s Disease and it always is worse when he is stressed and overtired.
He laughs, saying “I’ll probably be a pumpkin working in the ICU.”
Jaundice describes the yellowish discoloration of skin, sclera and mucous membranes when there is an excess of bilirubin in the blood. It is clinically evident with bilirubin levels > 2 mg/dl in older children and 4-5 mg/dl in infants.
The major source of bilirubin is the catabolism of hemoglobin.
Gilbert’s Disease is caused by a common genetic phenotype and can be found in up to 10% of the general population ( up to 36% in Africans and up to 3% in Asians). It is caused by a change in the promoter for the bilirbuin uridine diphosphate glucuronyl transferase gene.
The transcription of the gene is less active and therefore there is a relative deficiency of the enzyme. This causes a mild unconjugated hyperbilirubinemia (generally < 5 mg/dl) that is not associated with hepatocellular damage or hemolysis.
The hyperbilirubinemia clinically presents at times of fasting or stress. Gilbert’s Disease has not been associated with any specific morbidity or mortality. It may explain cases of prolonged neonatal “physiologic” jaundice.
Causes of unconjugated hyperbilirubinemia include:
- Cholestasis – intra- or extra-hepatic
- Liver disease
- Congenital hyperbilirubinemia – Crigler-Najjar Syndrome, Gilbert’s Disease
- Hemolytic anemia
- Fasting or malnutrition
- Medications – i.e. oral contraceptives, estrogens
- Reabsorption of extravastated blood
Questions for Further Discussion
1. What evaluation should be considered for unconjugated hyperbilirubinemia?
2. What are the causes of conjugated hyperbilirubinemia?
3. What causes physiologic jaundice in a neonate?
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
Information prescriptions for patients can be found at Pediatric Common Questions, Quick Answers for this topic: Jaundice.
To view current news articles on this topic check Google News.
Bakerman S. Bakerman’s ABC’s of Interpretive Laboratory Data. Third Edit. 1994:89.
Burchell B, Hume R. Molecular Genetic Basis of Gilbert’s Syndrome. J. Gastroenterology and Hepatology. 1999:14;960-9666.
Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1489.
ACGME Competencies Highlighted by Case
1. When interacting with patients and their families, the health care professional communicates effecively and demonstrates caring and respectful behaviors.
10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.
Donna M. D’Alessandro, MD
Associate Professor of Pediatrics, Children’s Hospital of Iowa
December 5, 2005