Document Detail

Fatal cerebral edema from late-onset ornithine transcarbamylase deficiency in a juvenile male patient receiving valproic acid.
MedLine Citation:
PMID:  16575347     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The aims of this report are to 1) present a rare case of fatal cerebral edema associated with late-onset ornithine transcarbamylase (OTC) deficiency in a juvenile male patient receiving valproic acid and 2) review the neuropathologic changes associated with the hyperammonemia. DESIGN: Case report. SETTING: A community hospital and a tertiary pediatric critical care unit. INTERVENTIONS: Carbohydrate administration, intravenous nitrogen excretion cocktail, and high-flux hemodialysis. MEASUREMENTS AND MAIN RESULTS: Despite aggressive therapy for presumed late-onset OTC deficiency, the patient rapidly developed fatal cerebral edema with tonsillar herniation. A liver biopsy confirmed OTC deficiency with approximately 3% of residual hepatic enzyme activity. Chromosomal analysis showed a normal male karyotype. A thorough molecular analysis of the coding region in the OTC gene Xp21.1 was completed, but mutations were not identified, suggesting an upstream or downstream abnormality. Severe brain swelling was evident on neuropathology, and histopathology showed Alzheimer type II astrocytes, neuronal cytoplasmic changes, and hypertrophy and eosinophilia of the small arterial walls. CONCLUSIONS: OTC deficiency is the most common urea cycle defect causing hyperammonemia. Late-onset presentations of OTC are infrequent, primarily affecting female patients. We present a rare case of a late-onset OTC deficiency in a juvenile male patient receiving valproic acid therapy who developed fatal cerebral edema. Valproic acid exacerbates acute elevations in ammonia and may contribute synergistically with ammonia to cerebral mitochondrial dysfunction.
Varsha Thakur; C Anthony Rupar; David A Ramsay; Ram Singh; Douglas D Fraser
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies     Volume:  7     ISSN:  1529-7535     ISO Abbreviation:  Pediatr Crit Care Med     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-09     Completed Date:  2006-11-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100954653     Medline TA:  Pediatr Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  273-6     Citation Subset:  IM    
Department of Paediatrics, Children's Hospital of Western Ontario, London, Ontario, Canada.
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MeSH Terms
Brain Edema / etiology*
Fatal Outcome
GABA Agents / adverse effects*
Hyperammonemia / drug therapy*
Ornithine Carbamoyltransferase Deficiency Disease / complications*,  genetics,  therapy
Valproic Acid / adverse effects*
Reg. No./Substance:
0/GABA Agents; 99-66-1/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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