WBR0631

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Microbiology, MainCategory::Pathology
Sub Category	SubCategory::Gastrointestinal, SubCategory::Neurology
Prompt	[[Prompt::A 2-year-old boy is brought by his mother to the emergency department for altered level of consciousness. Upon further questioning, the mother reports that the child has been suffering from low grade fever and a diffuse skin rash for the past few days. She also explains that she has been giving him aspirin to relive his symptoms. Rapid assessment in the ED is performed and blood work-up reveals hyperammonemia, hypoglycemia, and lactic acidemia. Computed tomography (CT) scan of the brain reveals diffuse edema. Which of the following molecular dysfunctions is most likely associated with this patient's condition?]]
Answer A	AnswerA::Absence of Golgi bodies in hepatocytes
Answer A Explanation	AnswerAExp::Reye's syndrome is not associated with the absence of Golgi bodies in hepatocytes.
Answer B	AnswerB::Loss of enzymatic activity in the mitochondria of the liver and brain
Answer B Explanation	AnswerBExp::Reye's syndrome is believed to be caused by the presence of pleomorphic mitochondria with non-uniform loss of enzymatic activity in the liver and brain. It is associated with aspirin ingestion in children.
Answer C	AnswerC::Collagen defect with abnormal mitotic activity in the liver
Answer C Explanation	AnswerCExp::Reye's syndrome is not associated with collagen defects or abnormal mitotic activity in the liver.
Answer D	AnswerD::Absence of enzymes within the lysosomal complex in the liver and brain
Answer D Explanation	AnswerDExp::Reye's syndrome is not associated with the absence of enzymes within the lysosomal complex.
Answer E	AnswerE::Presence of viral RNA molecules inhibiting protein degradation by the ubiquitin-proteasome pathway
Answer E Explanation	AnswerEExp::Reye's syndrome is not associated with the dysregulation of the ubiquitin-proteasome pathway.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient presents with Reye's syndrome, a form of acute hepatic encephelopathy characterized by the altered level of consciousness and suggestive findings on lab work-up, such as hyperammonenia, hypoglycemia, and lactic acidemia. Diffuse edema on neurological imaging is also characteristic of Reye's syndrome. In children, it is associated with the intake of aspirin that is usually ingested for its antipyretic properties during viral infections, such as VZV. Reye's syndrome is believed to be caused by presence of non-uniform loss of enzymatic activity in the mitochondria within cells of the liver and the brain, such as the loss of activity of pyruvate carboxylase. Exposure to chemical products that alter the intramitochondrial matrix, and low ATP:ADP ratio lead to the inhibition of the proper protein synthesis required by the mitochondria thus explaining the low enzymatic activity. Educational Objective: Reye's syndrome is an acute hepatic encephalopathy typically seen in children following ingestion of aspirin. It is characterized by altered level of consciousness and altered metabolic blood panel. Reye's syndrome is due to a mitochondrial dysfunction with characteristic pleomorphic mitochondria in the liver and the brain that have reduced enzymatic activity. References: Van Coster RN, De Vivo DC, Blake D, et al. Adult Reye's syndrome: a review with new evidence for a generalized defect in intramitochondrial enzyme processing. Neurology. 1991; 41(11):1815-21. Davies NW, Sharief MK, Howard RS. Infection-associated encephalopathies - their investigation, diagnosis, and treatment. J Neurol. 2006; 253:833-45. Glasgow JF. Reye's syndrome: the case for a causal link with aspirin. Drug Saf. 2006; 29(12):1111-21.]]
Approved	Approved::Yes
Keyword	WBRKeyword::Reye's syndrome, WBRKeyword::Aspirin, WBRKeyword::Encephalopathy, WBRKeyword::Hepatic Encephalopathy, WBRKeyword::VZV, WBRKeyword::Varicella zoster virus, WBRKeyword::Hypoglycemia, WBRKeyword::Hyperammonemia, WBRKeyword::Mitochondrial dysfunction, WBRKeyword::Microvesicular steatosis
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