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 (ED) for altered mental status. Upon further questioning, the mother reports that the child has been suffering from low grade fever and has had a diffuse skin rash for the past few days. She also explains that she has been giving him aspirin to relieve his symptoms. Rapid assessment in the ED is performed, and blood work-up demonstrates marked hyperammonemia, hypoglycemia, and lactic acidemia. Computed tomography (CT) scan of the brain shows 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 is diagnosed with Reye's syndrome, a form of acute hepatic encephelopathy in children characterized by altered mental status associated with hyperammonenia, hypoglycemia, and lactic acidemia. Diffuse edema on neurological imaging is also characteristic of Reye's syndrome. In children, Reye's syndrome is associated with administration of aspirin for viral infections (e.g. VZV). Reye's syndrome is thought to be caused by the presence of non-uniform loss of enzymatic activity in the mitochondria within cells in the liver and the brain, such as the loss of activity of pyruvate carboxylase. Exposure to chemical products that alter the intra-mitochondrial matrix, as well as low ATP:ADP ratio, leads to the inhibition of the proper protein synthesis required by the mitochondria and development of Reye's syndrome. 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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