WBR0649

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry
Sub Category	SubCategory::Gastrointestinal
Prompt	[[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 exam, 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?]]
Answer A	AnswerA::Increased hemoglobin breakdown
Answer A Explanation	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.
Answer B	AnswerB::Absent UDP-Glucuronyltransferase
Answer B Explanation	AnswerBExp::UDP-Glucuronyltransferase is absent or defective in Crigler-Najjar syndrome. The presentation of the patient is typical of this disease.
Answer C	AnswerC::Decreased bilirubin uptake by the liver
Answer C Explanation	AnswerCExp::Decreased bilirubin uptake by the liver is the main mechanism behind Gilbert syndrome not Crigler-Najjar.
Answer D	AnswerD::Bile outlet obstruction
Answer D Explanation	AnswerDExp::Bile outlet obstruction would usually lead to conjugated hyperbilirubinemia with deranged LFTs.
Answer E	AnswerE::Hydrolysis of conjugated bilirubin
Answer E Explanation	AnswerEExp::Hydrolysis of conjugated bilirubin is one of the mechanisms of neonatal hyperbilirubinemia.
Right Answer	RightAnswer::B
Explanation	[[Explanation:: 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 leading to 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. Educational Objective: Gilbert syndrome is a benign condition caused by decreased unconjugated bilirubin uptake by the liver. Reference: Jansen PLM. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr. 1999;158(S2):S089-S094. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Crigler-Najjar Syndrome, WBRKeyword::unconjugated hyperbilirubinemia, WBRKeyword::Bilirubin, WBRKeyword::Kernicterus
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