Abstract 800 Poster Session IV, Tuesday, 5/4 (poster 207)

Sialuria is a rare inborn error of metabolism in which excessive free sialic acid N-acetyl neuraminic acid) is synthesized. A defect in the feedback inhibition of UDP-GlcNAc-2-epimerase by the endproduct of the sialic acid synthetic pathway, CMP-sialic acid, is the mechanism underlying this overproduction. Only 4 patients have been documented to have such an enzymatic defect. Recent evidence suggests that sialuria is an autosomal dominant disorder ( AJHG 63:Abs 184, 1998). Given the variable expressivity in dominant disorders, and the paucity of sialuira cases, it is important for genetic and prognostic counseling to understand the phenotypic spectrum in this enzymopathy. Accordingly, we report the longitudinal follow-up of one of the original sialuria patients to age 11 years. Diagnosis was at age 10 months by enzyme assay. The molecular basis was recently found to be a missense mutation (R266Q) in a putative allosteric site. He presented with coarse facies, hoarse voice, hepatomegaly, inguinal hernias and massively elevated urine sialic acid. At 5 years, developmental testing found him to be average overall, but with weakness in visual, spatial and motor skills. At 8 1/2 years, he scored in the low average IQ range, with similar weakness being found. At approximately 9 years, he was diagnosed with ADHD. At 11 years, he developed intermittent abdominal pain and transaminase elevation (AST 173 U/L, ALT 572 U/L). Growth parameters were between the 45th to 60th percentiles. Neurologic examination and head MRI were normal. Pulmonary function testing showed minimal small airway obstruction. Skeletal survey demonstrated mild biconcave and biconvex deformities of the spine. Ultrasound showed a liver span of 19 cm, and cholelithiasis with normal biliary tree. Liver histology showed abundant cytoplasmic PAS (+) material and some abnormal mitochondria. Viral serology was negative and his LFTs returned to baseline (AST 36 U/L, ALT 164 U/L). Urine free sialic acid was greater than 8,000 nmol/mg Cr (20× normal). Although he has coarse facial features and massive hepatomegaly, he has not shown evidence of liver failure and has continued to show normal growth and relatively normal development to age 11 years. Sialuria should be considered in the differential diagnosis of a patient with a phenotype suggestive of a mucopolysaccharidoses or oligosaccharidoses in the absence of developmental regression or dysostosis multiplex. We recommend close monitoring of liver and pulmonary function in sialuria patients.