A 4-week-old girl is brought to the office due to yellowing of the skin. The parents first noticed the symptoms a week ago and the patient's skin has become progressively more yellow. She was born at term to a primigravida mother via spontaneous vaginal delivery. The pregnancy and delivery were unremarkable, and the patient was discharged at 48 hours of life. She is exclusively breastfed and is gaining weight appropriately. Bowel movements occur once or twice daily, but the stool has become increasingly light in color and is now pale gray. Examination reveals scleral icterus and jaundice to the umbilicus. The liver is palpable 4 cm below the costal margin and the spleen tip is palpable. Laboratory results are as follows:
| Complete blood count | |
| Hemoglobin | 11.0 g/dL |
| Liver function studies | |
| Total bilirubin | 12.8 mg/dL |
| Direct bilirubin | 8.1 mg/dL |
| Aspartate aminotransferase (SGOT) | 52 U/L |
| Alanine aminotransferase (SGPT) | 70 U/L |
Which of the following is the most likely primary mechanism for this patient's hyperbilirubinemia?
Show Explanatory Sources
This neonate's direct hyperbilirubinemia is concerning for biliary atresia (BA), a progressive and potentially fatal disease in which extrahepatic bile ducts become fibrosed and ultimately destroyed.
Bilirubin, a product of heme breakdown, is normally conjugated in the liver and then transported through the bile ducts and gallbladder to the intestines for excretion in stool. Newborns with BA have normal bilirubin production and conjugation but decreased bilirubin excretion due to bile duct obstruction (cholestasis). Although patients are asymptomatic at birth, lack of bile in the intestines leads to pale stools at age 2-8 weeks. In addition, the retention of bilirubin in hepatocytes causes hepatomegaly, and increased direct bilirubin in plasma results in jaundice, as seen in this patient. Splenomegaly may be observed but is typically a late finding (age >3 months) suggestive of cirrhosis; the spleen tip is sometimes palpable in healthy newborns.
The Kasai procedure (hepatoportoenterostomy) diverts bile to the small intestine and is most successfully performed before age 2 months; liver transplantation is often ultimately required. Untreated disease can lead to cirrhosis, portal hypertension, and death.
(Choice A) Decreased conjugation of bilirubin due to impaired uridine diphosphate glucuronosyltransferase activity occurs with Gilbert and Crigler-Najjar syndromes. Both conditions are characterized by varying degrees of jaundice and indirect (rather than direct) hyperbilirubinemia.
(Choice C) Decreased hepatic uptake of bilirubin can occur with certain drugs (eg, rifampin) or reduced hepatic blood flow (eg, congestive heart failure). Increased indirect bilirubin would be expected because bilirubin cannot enter the hepatocytes for conjugation.
(Choice D) Breastfeeding failure jaundice, seen in the first few days of life, is caused by inadequate intake and results in a slower transit and elimination of bilirubin. Breast milk jaundice, which peaks at age 2 weeks, is caused by increased beta-glucuronidase in breast milk, which deconjugates intestinal bilirubin. Both conditions result in increased enterohepatic circulation and indirect hyperbilirubinemia.
(Choice E) Increased bilirubin production is seen in hemolytic disease (eg, sickle cell disease, ABO incompatibility) due to the destruction of red blood cells (RBCs). In addition, increased RBC turnover, seen in physiologic jaundice of newborns, occurs due to increased hematocrit levels and a shorter lifespan of fetal RBCs. Indirect bilirubinemia is seen in both conditions.
Educational objective:
Biliary atresia is the fibrosis and obliteration of extrahepatic bile ducts. Bilirubin production and conjugation continue at a normal rate, but bilirubin cannot be excreted into the intestines (leading to pale stools) and accumulates in the blood (causing direct hyperbilirubinemia and jaundice).