Three defects affecting sialylation are known to date: CDG-IIf, HIBM, and sialuria. Sialuria patients have a defect in uridine-5'-diphosphate-N-acetylglucosamine-2-epimerase /N-acetylmannosamine kinase (GNE/MNK) leading to an overproduction of CMPNeuAc.
Abnormal glycosylation with hypersialylated O-glycans in patients with Sialuria. Biochim Biophys Acta 2006;1762:598-607.
Mutations in GNE/MNK have been described in hereditary inclusion body myopathy (hIBM), in distal myopathy with rimmed vacuoles (DMRV), and in sialuria.
Sialuria. Sialuria, formerly called French-type sialuria, is an autosomal dominant inborn error of metabolism in which the feedback control mechanism in the biosynthesis of CMP-NeuAc is lost.
Laboratory findings: Highly increased concentrations of urinary free sialic acid (NeuAc) and of fibroblast free sialic acid have been found in patients with sialuria (184, 185).
Another remarkable difference between N- and O-glycan deficiencies is that N-glycan deficiencies generally have recessive inheritance, whereas in some of the O-glycan biosynthesis diseases, such as sialuria and HME, inheritance is autosomal dominant.
A first study on profiling of total serum O-glycans described alterations in the glycans of patients with sialuria (Wopereis S, unpublished data).
This makes it possible to differentiate patients with isolated neuraminidase deficiency, who excrete bound N-acetylneuraminic acid, from patients with Salla disease or French type sialuria, who excrete excess free N-acetylneuraminic acid in urine (13).