Clinical course and biochemistry of sialuria

Sialuria is a rare inborn error of metabolism in which excessive free siali c acid (N-acetylneuraminic acid, NeuAc) is synthesized. A defect in the fee dback inhibition of UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase by the end-product of the sialic acid synthetic pathway, CMP-NeuAc, is the mechan ism underlying this overproduction. Recent evidence suggests that sialuria is an autosomal dominant disorder. Only five patients have been documented to have such an enzymatic defect. We report a longitudinal study of one of the original sialuria patients, to age 11 years. Although he has coarse fea tures and massive hepatomegaly, he has shown normal growth and relatively n ormal development. Pulmonary function testing showed minimal small airway o bstruction. At 11 years, he developed intermittent abdominal pain and trans ient transaminase elevation above his baseline. Sialuria should be consider ed in the differential diagnosis of a patient with a phenotype suggestive o f a mucopolysaccharidosis or oligosaccharidosis in the absence of developme ntal regression or prominent dysostosis multiplex. We recommend close monit oring of liver and pulmonary function in sialuria patients.