Sialuria in a Portuguese girl: Clinical, biochemical, and molecular characteristics

Sialuria, a disorder of sialic acid (NeuAc) metabolism characterized by inc reased free NeuAc in the cytoplasm of cells, is due to failure of CMP-Neu5A c to feedback inhibit UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We now describe the fifth patient in the world with sialuria, a 7-year-old Por tuguese girl with developmental delay, hepatomegaly, coarse facies, and uri nary excretion of 19 mu mol of free NeuAc/mg creatinine, The patient's fibr oblasts stored excess free NeuAc in the cytosolic fraction, and fibroblast UDP-GlcNAc 2-epimerase activity was only 26% inhibited by 100 mu M CMP-Neu5 Ac (normal, 79%). The patient's UDP-GlcNAc 2-epimerase gene displayed an R2 66Q mutation in only one allele, consistent with known sialuria mutations a nd with the proposed dominant nature of this disorder. Extensive descriptio n of sialuria patients will help to define the clinical and biochemical spe ctrum of this disease. (C) 1999 Academic Press.