title: Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency.
abstract: Ornithine transcarbamylase deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. A heterozygous female patient first presented with protein intolerance, attacks of vomiting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she developed severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 micromol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a specific therapy for the inborn metabolic disease, ammonia concentrations fell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.
authors.affiliation: Department of Neurology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Oechsner
authors.forename: C
authors.initials: C
authors.lastname: Steen
authors.forename: H J
authors.initials: HJ
authors.lastname: Stürenburg
authors.forename: A
authors.initials: A
authors.lastname: Kohlschütter
mesh_terms: D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D000641:Ammonia / Q000097:blood*; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D001928:Brain Diseases, Metabolic / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology; D003937:Diagnosis, Differential; D004359:Drug Therapy, Combination; D017029:Epilepsy, Complex Partial / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D000641:Ammonia