A 4-week-old boy is brought to the clinic due to a change in bowel pattern. The patient was born at term and has been having a bowel movement after most feeds since birth. However, over the past week he has been stooling only 1 or 2 times a day, and the color has become consistently paler. The parents have also noticed progressive yellowing of the eyes over the last few weeks. The patient is exclusively breastfed and is in the 25th percentile for weight. He takes no medications. Temperature is 37.1 C (98.8 F) . Physical examination shows a well-appearing infant with scleral icterus and jaundice of the face and chest. The abdomen is soft and bowel sounds are present. The liver is enlarged. The remainder of the examination is normal. Total bilirubin is 12.5 mg/dL. Hepatic ultrasound reveals absence of the gallbladder and confirms hepatomegaly. Which of the following laboratory patterns is most likely to be present in this patient?

Question

Quizplus · Accepted Answer

11ec25c8_d674_5dbd_bc81_d9fa9732a3d4_MD0003_00 This infant has findings concerning for biliary atresia, a neonatal disorder characterized by progressive fibrosis and obliteration of extrahepatic bile ducts. Conjugated bilirubin is produced by hepatocytes but cannot be transported through the fibrotic ducts, leading to cholestasis. Affected infants usually develop jaundice and hepatomegaly at age 2-8 weeks. Decreased bile excretion into the intestines also leads to acholic stools (eg, pale, clay-colored). Untreated disease can lead to splenomegaly due to progressive cirrhosis and portal hypertension. extrahepatic bile ducts Laboratory evaluation reveals elevated total and direct bilirubin levels. Bile duct destruction leads to elevated gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase; aminotransferases are usually normal or mildly elevated. Reticulocyte count is normal due to the absence of hemolysis. Abdominal ultrasound may reveal the triangular cord sign (fibrous remnants above the porta hepatis) or a small or absent gallbladder, findings highly suggestive of biliary atresia. Definitive diagnosis requires intraoperative cholangiography or liver biopsy. If biliary atresia is confirmed, hepatoportoenterostomy (Kasai procedure) is performed to reestablish bile flow to the small intestine. However, most children with biliary atresia eventually require a liver transplant. (Choice B) Hemophagocytic lymphohistiocytosis (HLH) is a systemic inflammatory condition that can present with elevated direct bilirubin and GGT (due to cholestasis) and with cytopenias and decreased reticulocytes (due to bone marrow failure). In contrast to this patient, infants with HLH have a normal gallbladder and are typically febrile and ill-appearing. (Choice C) Certain rare, genetic causes of cholestasis, such as progressive familial intrahepatic cholestasis, cause direct hyperbilirubinemia with paradoxically normal GGT. Although the presentation is similar to biliary atresia (eg, jaundice, acholic stools), absence of the gallbladder is highly suggestive of biliary atresia. (Choice D) An elevated reticulocyte count in a child with jaundice and normal direct bilirubin suggests hemolysis. However, this patient's acholic stools and absent gallbladder make biliary atresia more likely. (Choice E) Breast milk jaundice is likely due to high levels of beta-glucuronidase in breast milk, which deconjugates intestinal bilirubin and increases enterohepatic circulation. Affected infants have indirect (not direct) hyperbilirubinemia and normal GGT. Unlike in this case, breast milk jaundice peaks at 2 weeks of life and is not associated with pale stools or an absent gallbladder. Educational objective: Biliary atresia is a neonatal disorder in which extrahepatic bile ducts develop progressive fibrosis. Patients have jaundice, pale stools, and a small or absent gallbladder. Laboratory findings include direct hyperbilirubinemia, normal reticulocyte count, and elevated gamma-glutamyl transpeptidase. References: A practical approach to the pathology of neonatal cholestatic liver disease. (http://www.ncbi.nlm.nih.gov/pubmed/31455583) Biliary atresia: clinical lessons learned. (http://www.ncbi.nlm.nih.gov/pubmed/25658057)

A 4-Week-Old Boy Is Brought to the Clinic Due to a Change