(850) Fatal Reye Syndrome: Revisiting the Rare Disease

Introduction: Reye syndrome is a rare non-inflammatory encephalopathy with hyperammonemia and liver failure. Its incidence peaked in the 1980’s and was predominantly described in children with viral illness and salicylate exposure. Recent evidence supports certain inborn errors of metabolism and mitochondrial dysfunction may predispose children to develop the disease. Public health campaign against aspirin use in children significantly decreased Reye syndrome’s incidence, while concomitantly reducing pediatricians’ clinical experience with the disease.

Description: A 2-year-old typically developing male with immune thrombocytopenic purpura on escalating doses of eltrombopag and unilateral renal agenesis presented to ED with 2 days of vomiting and 1 day of lethargy. Initial workup revealed hyperammonemia, elevated transaminases and a normal head CT. Viral PCR was positive for rhino/enterovirus. He had no known exposure to salicylates. Following admission to the Pediatric ICU with consulting genetic/metabolic and hepatology teams, his mental status rapidly deteriorated and he began hyperventilating. He required intubation for airway protection. Hyperammonemia was initially refractory to management with an Ammonul infusion and continuous veno-venous hemodiafiltration. Over the next 24 hours, he developed clinical signs of herniation. Head CT confirmed diffuse cerebral edema with transtentorial and tonsillar herniation. Despite normalization of the ammonia 48 hours after presentation, he lost all brainstem reflexes and developed profound hemodynamic instability. Repeat scans demonstrated worsening herniation. His parents decided to compassionately discontinue mechanical support and he died just shy of 72 hours after presentation. Autopsy revealed microvesicular steatosis of the liver and diffuse cerebral edema consistent with Reye syndrome. No definitive mitochondrial disorder was identified.

Discussion: Cases of Reye syndrome are extremely rare with about 2 reported cases per year in the United States. With clinician lack of exposure to Reye syndrome in recent decades, it may be under recognized and under reported. This case calls for efforts to characterize the current incidence of Reye syndrome and better understand risk factors beyond the classic salicylate exposure and disorders of metabolism.