View source for WBR0649

 {{WBRQuestion
|QuestionAuthor= {{SSK}} (Reviewed by Serge Korjian)
|ExamType=USMLE Step 1
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|Prompt=A 2-week-old child is brought to the neonatal care clinic for irritability and poor feeding. The mother also reports that she has noticed her child's eyes are unusually yellow. On physical examination, you notice that the child is poorly responsive and is markedly icteric and jaundiced. Lab tests ordered show normal liver function tests. Serum bilirubin levels is detected to be 28 mg/dL with absent conjugated bilirubin from the serum. Which of the following mechanisms is most likely responsible for this patient's presentation?
|Explanation=[[Image:Bilirubin_metabolism.jpg|900px]]

Crigler-Najjar syndrome Type I is a serious but rare genetic disorder characterized by a mutation of the UGT1A1 gene that codes for the UDP-glucuronyltransferase enzyme. UDP-glucuronyltransferase is the enzyme responsible for conjugating bilirubin for excretion into bile. With this enzyme absent, unconjugated bilirubin accummulates, usually very early in life, leading to serious complications. In young children, the elevated unconjugated bilirubin can cross the blood brain barrier and deposit in the brain causing a condition known as kernicterus, the leading cause of death in Crigler-Najjar Type 1. Typically patients have very elevated unconjugated bilirubin levels with normal liver function tests. Most patients usually die early in life or suffer severe neurologic sequalae.
|AnswerA=Increased hemoglobin breakdown
|AnswerAExp=Increased hemoglobin breakdown is seen in patients with hemolysis. Our patient's CBC, retic count and blood smear showed no indication of hemolysis. Increased hemoglobin breakdown is not seen in Crigler-Najjar type 1.
|AnswerB=Absent UDP-Glucuronyltransferase
|AnswerBExp=UDP-Glucuronyltransferase is absent or defective in Crigler-Najjar syndrome. The presentation of the patient is typical of this disease.
|AnswerC=Decreased bilirubin uptake by the liver
|AnswerCExp=Decreased bilirubin uptake by the liver is the main mechanism behind Gilbert syndrome not Crigler-Najjar.
|AnswerD=Bile outlet obstruction
|AnswerDExp=Bile outlet obstruction would usually lead to conjugated hyperbilirubinemia with deranged LFTs.
|AnswerE=Hydrolysis of conjugated bilirubin
|AnswerEExp=Hydrolysis of conjugated bilirubin is one of the mechanisms of neonatal hyperbilirubinemia.
|EducationalObjectives=Gilbert syndrome is a benign condition caused by decreased unconjugated bilirubin uptake by the liver.
|References=Jansen PLM. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr. 1999;158(S2):S089-S094.
|RightAnswer=B
|WBRKeyword=Crigler-Najjar Syndrome, Unconjugated hyperbilirubinemia, Bilirubin, Kernicterus, UDP-glucuronyltransferase
|Approved=Yes
}}