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|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=Gastrointestinal
|SubCategory=Gastrointestinal
|Prompt=A 34 year old healthy man presents to the primary care clinic for a general check-up. The man has no complaints except some fatigue during the day, but he relates this to his stressful life style. Physical exam is unremarkable except for mild scleral icterus. The primary care physician decides to order some tests to rule out any serious illness. Lab results return with a normal CBC, reticulocyte count, and blood smear. Transaminases, alkaline phosphatase, and GGT are also all within normal range. Indirect bilirubin is noted to be 2.6 mg/dL with direct bilirubin below the upper limit of normal. The patient remembers that he was noted to have an elevated indirect bilirubin several years earlier but his work-up back then also came back normal. Which of the following pathological mechanisms is involved in this patient's condition?
|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?
|Explanation=[[Image:Bilirubin_metabolism.jpg|900px]]
|Explanation=[[Image:Bilirubin_metabolism.jpg|900px]]


Gilbert syndrome is a benign condition leading to elevated indirect bilirubin levels. Its main pathophysiologic mechanism is the decreased uptake of unconjugated bilirubin by the liver, although some decrease in the efficiency of UDP-glucuronyltransferase can be noted in some patients. Usually patients present with asymptomatic jaundice. Fatigue can be present in some patients. The increase in bilirubin is usually triggered by fasting, febrile illness, alcohol, exercise, or stress. It is important to rule out any other disease processes in patients suspected to have Gilbert syndrome. Lab tests include a CBC with reticulocyte count and blood smear for any signs of hemolysis, and liver function tests for any signs of liver disease. Gilbert's syndrome doesn't require treatment. Patients with Gilbert syndrome have an excellent prognosis and the unconjugated hyperbilirubinemia does not cause any health problems.


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.
Educational Objective: Gilbert syndrome is a benign condition caused by decreased unconjugated bilirubin uptake by the liver.
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Reference:
Reference:


Owens D, Evans J. Population studies on Gilbert's syndrome. J Med Genet. 1975;12(2):152-6.
Jansen PLM. Diagnosis and management of Crigler-Najjar syndrome. Eur J Pediatr. 1999;158(S2):S089-S094.
|AnswerA=Increased hemoglobin breakdown
|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 Gilbert syndrome
|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
|AnswerB=Absent UDP-Glucuronyltransferase
|AnswerBExp=UDP-Glucuronyltransferase is absent or defective in Criggler-Najjar syndrome. The presentation would be more severe in a much younger patient with associated liver dysfunction.
|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
|AnswerC=Decreased bilirubin uptake by the liver
|AnswerCExp=Decreased bilirubin uptake by the liver is the main mechanism behind Gilbert syndrome.
|AnswerCExp=Decreased bilirubin uptake by the liver is the main mechanism behind Gilbert syndrome not Crigler-Najjar.
|AnswerD=Bile outlet obstruction
|AnswerD=Bile outlet obstruction
|AnswerDExp=Bile outlet obstruction would usually lead to conjugated hyperbilirubinemia with deranged LFTs.
|AnswerDExp=Bile outlet obstruction would usually lead to conjugated hyperbilirubinemia with deranged LFTs.
|AnswerE=Hydrolysis of conjugated bilirubin
|AnswerE=Hydrolysis of conjugated bilirubin
|AnswerEExp=Hydrolysis of conjugated bilirubin is one of the mechanisms of neonatal hyperbilirubinemia.
|AnswerEExp=Hydrolysis of conjugated bilirubin is one of the mechanisms of neonatal hyperbilirubinemia.
|RightAnswer=C
|RightAnswer=B
|WBRKeyword=Gilbert Syndrome, unconjugated hyperbilirubinemia, bilirubin
|WBRKeyword=Crigler-Najjar Syndrome, unconjugated hyperbilirubinemia, Bilirubin, Kernicterus
|Approved=No
|Approved=No
}}
}}

Revision as of 06:11, 24 October 2013
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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