1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-7-64-a 10.15844/pedneurbriefs-7-8-10 Toxic and Infective Disorders Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Valproate-Induced Fatal Hepatotoxicity http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 08 1993 01 07 2016 7 8 64 64 Copyright: © 1993 The Author(s) 1993 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatotoxic effects in a child receiving valproate and carnitine

An 18 month old infant with fatal VPA-related hepatic toxicity is reported from Children’s Mercy Hospital, Kansas City, MO, and the Mayo Clinic, Rochester, MN.

 Alpers Disease Hepatic Dysfunction Valproate Therapy

An 18 month old infant with fatal VPA-related hepatic toxicity is reported from Children’s Mercy Hospital, Kansas City, MO, and the Mayo Clinic, Rochester, MN. The infant had received L-carnitine supplements and did not have Alpers disease. The child presented at 15 months with developmental delay, periodic vomiting, ataxia, chorea, hypotonia, areflexia, and nocturnal myoclonus. VPA, 15 mg/kg per day, supplemented with L-carnitine, 200 mg 4xdaily, resulted in initial partial control of the chorea and myoclonus. Relapse after 9 weeks therapy was accompanied by lethargy, vomiting, and hepatic dysfunction, resulting in death in 6 weeks. The liver was small, atrophic, and yellow at autopsy, and the brain showed neuronal loss and gliosis in the brain stem, cerebellar nuclei, and spinal cord. [1]

COMMENT. The authors contend that the clinical features and pathological findings ruled out Alpers disease, but an undiscovered explanation for the neurological disorder and some contributory metabolic cause could not be definitely excluded. Nonetheless, this experience demonstrates the potential hazard of valproic acid therapy, particularly in young and neurologically impaired children, and carnitine supplements are not a prophylactic panacea against VPA liver toxicity.

Fanconi syndrome associated with valproate therapy for seizures in two developmentally delayed children, aged 4 and 9 years, is reported from Harvard Medical School, and Northampton Area Pediatrics, MA. [2]

 Murphy JV Groover RV Hodge C Hepatotoxic effects in a child receiving valproate and carnitine J Pediatr 1993 Aug 123 2 318 320 10.1016/S0022-3476(05)81711-1 8345435 Lande MB Kim MS Bartlett C Guay-Woodford LM Reversible Fanconi syndrome associated with valproate therapy J Pediatr 1993 Aug 123 2 320 322 10.1016/S0022-3476(05)81712-3 7688423