title: Valproate-induced hyperammonemia in juvenile ceroid lipofuscinosis (Batten disease).
abstract: OBJECTIVE
  Valproate-induced hyperammonemia (VHA) and hyperammonemic encephalopathy (VHE) are well-known complications of valproate (VPA) treatment. Currently recognised risk factors for VHE include a high VPA dosage, the need for polytherapy and long duration of treatment. Despite the severe nature of the epilepsy, presence of concomitant psychiatric manifestations, and frequent need for poly-pharmacy associated with juvenile ceroid lipofuscinosis (JNCL, Batten disease) neither this disorder nor other subtypes of neuronal ceroid lipofuscinosis have previously been identified as risk factors for VHA/VHE. The aim of the present publication is to describe four cases with VHE in a well-defined Danish population of JNCL.
  
  
  METHODS
  An examination of medical records of all 35 patients with JNCL in Denmark was conducted and revealed fourteen patients treated with VPA.
  
  
  RESULTS
  Four patients treated with VPA developed VHE. All patients were prescribed VPA in standard dosages, had normal plasma concentrations of VPA and received antiepileptic drug (AED) polytherapy. Symptoms occurred shortly after commencement or increase in dose of VPA, and were quickly reversible upon discontinuation of VPA. Carnitine supplement was administrated in two patients, which resulted in resolution of symptoms and normalized ammonium levels.
  
  
  CONCLUSIONS
  Patients with JNCL are in great risk of developing VHA and VHE due to a high rate of polytherapy. Furthermore, studies have shown that carnitine level can be depressed in JNCL, which may increase the risk of VHA and VHE. We recommend that increased attention should be given to these patients.
authors.affiliation: Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark.
authors.forename: Erling P
authors.initials: EP
authors.lastname: Larsen
authors.affiliation: Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Brendstrupgaardsvej 100, 8200 Aarhus N, Denmark. Electronic address: john.oestergaard@skejby.rm.dk.
authors.forename: John R
authors.initials: JR
authors.lastname: Ostergaard
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001927:Brain Diseases / Q000139:chemically induced*; D002331:Carnitine / Q000008:administration & dosage; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009472:Neuronal Ceroid-Lipofuscinoses / Q000188:drug therapy* / Q000503:physiopathology; D014635:Valproic Acid / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014803:Vitamin B Complex; D014635:Valproic Acid; D002331:Carnitine
keywords: Batten disease; Carnitine; Hyperammonemia; Juvenile ceroid lipofuscinosis; Valproate; Valproate-induced hyperammonemic encephalopathy