Biochemical monitoring of sodium valproate in children

s 75 Biochemical monitoring of sodium valproate in children W. Whitehouse, H. Seddon, M. Preece & A. Green Department of Paediatric Neurology and the Regional Inherited Metabolic Disease Laboratory, Birmingham Children’s Hospital, Birmingham, UK Sodium valproate (VPA) is an effective anti-epileptic drug (AED) in infancy. However. it has been associated with sometimes fatal adverse effects on liver function. Twenty-two children under 5 years of age prescribed VPA were therefore studied before or shortly after starting treatment and 1 and 3 months later. Plasma VPA, urea, creatinine, albumin, liver enzymes, lactate, ammonia (NHj), free fatty acids, 3-hydxroxybutyrate, glucose, free and total carnitine, quantitative plasma amino acids and urine organic and amino acids were analysed. Mean plasma free camitine was 41 ~mol/l(flO wmol/l) before VPA, falling to 25 pmol/l(&8 ,umol/l) after 3 months (reference range of 15-53 pmol/l); and to below the reference range in one patient. Moderate increases in NH3 (between 50 and 90 pmol/l) were seen in 53% of patients; no IEM was found. Aspartate transaminase was > 50 III/l in 36% of patients with no apparent adverse effects. Two patients showed marked increases in NH3 (99 and 124 lmol/l) with concurrent increases in lactate (5.9 and 4.5 pmol/l respectively) and their alkaline phosphatase (ALP) was > 1000 IU/l. Cytochrome c oxidase deficiency was diagnosed in one, the other died unexpectedly with no diagnosis. Plasma lactate, NH3 and ALP may, therefore, be predictors of a metabolic problem likely to be compounded by VPA.