A 3-week-old boy is brought to the office due to worsening jaundice. A week ago, the parents noticed that the patient's eyes and face looked yellow, and his trunk has become increasingly yellow over the last 2 days. They describe his stool as consistently pale. The patient is exclusively breastfed and has been feeding well. The pregnancy and delivery were uncomplicated. Maternal blood type is O positive, and routine prenatal studies were normal. Temperature is 37.2 C (99 F), pulse is 140/min, and respirations are 50/min. Capillary refill is

Question

A 3-week-old boy is brought to the office due to worsening jaundice.  A week ago, the parents noticed that the patient's eyes and face looked yellow, and his trunk has become increasingly yellow over the last 2 days.  They describe his stool as consistently pale.  The patient is exclusively breastfed and has been feeding well.  The pregnancy and delivery were uncomplicated.  Maternal blood type is O positive, and routine prenatal studies were normal.  Temperature is 37.2 C (99 F), pulse is 140/min, and respirations are 50/min.  Capillary refill is <2 seconds.  Examination shows jaundice and hepatomegaly.  Laboratory results are as follows:  Which of the following is the most appropriate diagnostic test?

Quizplus · Accepted Answer

11ec25c8_d672_3ad9_bc81_37957bd57785_MD0003_00 This infant's pale stools, hepatomegaly, and direct hyperbilirubinemia are concerning for neonatal cholestasis. The most common cause in young infants is biliary atresia (BA), a progressive, fibrotic obliteration of the extrahepatic bile ducts. In this condition, bilirubin is conjugated normally by the liver but cannot be excreted due to the mechanical obstruction of biliary flow. extrahepatic bile ducts conjugated Newborns are initially asymptomatic but develop jaundice, acholic stools (due to absent biliary pigment), and dark urine (due to renal excretion of bilirubin) at age 2-8 weeks. Progressive disease can lead to fibrosis and hepatomegaly, as seen in this patient. Laboratory studies reveal conjugated hyperbilirubinemia, and transaminases are often normal but may be elevated with advanced disease. Initial evaluation includes an abdominal ultrasound, which classically shows an abnormal or absent gallbladder because it is also affected by the fibroobliterative process. Liver biopsy should be performed in all patients with suspected BA to exclude alternative diagnoses because a delay (beyond age 8 weeks) in diagnosis and surgical intervention for BA is associated with a higher risk of liver transplantation and mortality. Classic histologic findings include intrahepatic bile duct proliferation, portal tract inflammation and edema, and fibrosis. (Choices A and D) A positive direct antiglobulin test confirms isoimmune hemolytic disease (eg, ABO incompatibility) in which maternally derived antibodies cause hemolysis of neonatal red blood cells (RBCs) and therefore jaundice within the first few days of life. Hereditary spherocytosis, an inherited RBC membrane defect confirmed by spherocytes on peripheral smear, can also lead to neonatal hemolysis due to poor RBC deformability. However, hemolytic conditions are characterized by unconjugated (not conjugated) hyperbilirubinemia from RBC breakdown. Moreover, splenomegaly is often seen in hereditary spherocytosis, but hepatomegaly is not. (Choice B) Crigler-Najjar and Gilbert syndromes are inherited deficiencies of UDP glucuronosyltransferase, the enzyme responsible for bilirubin conjugation. Unlike this patient, those with these conditions have jaundice due to unconjugated hyperbilirubinemia, and pale stools would not be seen. UDP glucuronosyltransferase (Choice E) Alpha-1 antitrypsin (AAT) deficiency is a rare cause of neonatal cholestasis due to the intracellular accumulation of AAT, but elevated transaminases would be expected. Educational objective: Biliary atresia is characterized by fibrotic obliteration of the extrahepatic bile duct and presents at age 2-8 weeks with direct hyperbilirubinemia (eg, jaundice, acholic stools, dark urine). Liver biopsy should be performed in all patients with suspected biliary atresia; it shows intrahepatic bile duct proliferation and portal tract inflammation. References: Conjugated hyperbilirubinemia in children. (http://www.ncbi.nlm.nih.gov/pubmed/22753787) Biliary atresia. (http://www.ncbi.nlm.nih.gov/pubmed/30725947)

A 3-Week-Old Boy Is Brought to the Office Due to Worsening