Sir.—In his recent commentary in the March issue of the Journal (130:241, 1976), Dr Thaler has attempted to review the complex and slowly evolving story of the pathogenic mechanisms in Reye syndrome. One point in the article, however, is at best highly speculative. Although it is attractive to implicate orotic acid accumulation as an explanation for the fatty changes in the liver and other viscera, the currently available data lend no support to this concept.
Of the 13 patients with Reye syndrome discussed in the literature in whom urinary orotic acid excretion was measured during the early stages of disease, nine demonstrated normal excretion and four had slightly elevated excreation.1.2 None of the patients studied had orotic acid excretion approaching that observed in isolated ornithine transcarbamylase (OTC) deficiency. We have subsequently measured urine orotic acid in five additional patients with Reye syndrome, and none have had elevated excretion.