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The High Incidence of Valproate Hepatotoxicity in Infants May Relate to Familial Metabolic Defects

Published online by Cambridge University Press:  18 September 2015

R.E. Appleton ,
K. Farrell ,
D.A. Applegarth ,
J.E. Dimmick ,
L.T.K. Wong  and
A.G.F. Davidson
R.E. Appleton
Affiliation:
Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, Vancouver
K. Farrell*
Affiliation:
Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, Vancouver
D.A. Applegarth
Affiliation:
Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, Vancouver Department of Pathology, British Columbia's Children's Hospital, University of British Columbia, Vancouver
J.E. Dimmick
Affiliation:
Department of Pathology, British Columbia's Children's Hospital, University of British Columbia, Vancouver
L.T.K. Wong
Affiliation:
Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, Vancouver
A.G.F. Davidson
Affiliation:
Department of Pediatrics, British Columbia's Children's Hospital, University of British Columbia, Vancouver
*
British Columbia's Children's Hospital, 4480 Oak Street, Vancouver, British Columbia, Canada V6H 3V4
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Abstract:

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The incidence of fatal hepatic failure associated with valproic acid (VPA) therapy is highest in children under the age of three years, particularly in those with developmental delay. The pathogenesis of VPA hepatotoxicity is unclear but may relate to the accumulation of a toxic metabolite of VPA which impairs fatty-acid oxidation. We describe two unrelated infants with developmental delay who developed hepatic failure while receiving VPA. Siblings of both children subsequently developed hepatic steatosis and intractable seizures without being exposed to VPA. This suggests that that the two children who developed liver failure when receiving VPA may have had a familial metabolic disorder. Familial metabolic disorders may account partly for the higher incidence of fatal hepatotoxicity described in infants receiving VPA.

Résumé:

RÉSUMÉ:

L'incidence de l'insuffisance hépatique fatale associée au traitement par l'acide valproïque (AVP) est plus élevée chez les enfants en bas de trois ans, particulièrement chez ceux qui ont un retard de développement. La pathogenèse de l'hépatotoxicité due à l'AVP n'est pas claire, mais elle peut être en relation avec l'accumulation d'un métabolite toxique de l'AVP qui entrave l'oxidation des acides gras. Nous décrivons le cas de deux nourrissons non apparentés ayant un retard de développement, qui ont développé une insuffisance hépatique sous AVP. Des membres de la fratrie des deux enfants ont ultérieurement développé une stéatose hépatique et des convulsions résistantes au traitement sans exposition à l'AVP. Ceci suggère que les deux enfants qui ont développé une insuffisance hépatique sous AVP avaient peut-être une anomalie métabolique familiale. Les anomalies métaboliques familiales peuvent être en partie responsables de l'incidence plus élevée d'hépatotoxicité fatale décrite chez les nourrissons recevant de l'AVP.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 17 , Issue 2 , May 1990 , pp. 145 - 148
Copyright
Copyright © Canadian Neurological Sciences Federation 1990

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