Sialuria is a rare disorder that affects development. Infants with sialuria are often born with a yellow tint to the skin and the whites of the eyes (neonatal jaundice), an enlarged liver and spleen (hepatosplenomegaly), and unusually small red blood cells (microcytic anemia). They may develop a somewhat flat face and distinctive-looking facial features that are described as "coarse." Temporarily delayed development and weak muscle tone (hypotonia) have also been reported.

Young children with sialuria tend to have frequent upper respiratory infections and episodes of dehydration and stomach upset (gastroenteritis). Older children may have seizures and learning difficulties. In some affected children, intellectual development is nearly normal.

The features of sialuria vary widely among affected people. Many of the problems associated with this disorder appear to improve with age, although little is known about the long-term effects of the disease. It is likely that some adults with sialuria never come to medical attention because they have very mild signs and symptoms or no health problems related to the condition.

Fewer than 20 cases of sialuria have been described worldwide. There are probably more people with the disorder who have not been diagnosed, as sialuria can be difficult to detect because of its variable features.

Variants (also called mutations) in the GNE gene cause sialuria. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions, including cell movement (migration), the attachment of cells to one another (adhesion), signaling between cells, and inflammation.

A feedback system helps control the amount of sialic acid produced in cells. This system shuts off the enzyme produced from the GNE gene when no more sialic acid is needed. The variants responsible for sialuria disrupt this feedback mechanism, resulting in an overproduction of sialic acid. This simple sugar builds up within cells and is excreted in urine. Researchers are working to determine how an accumulation of sialic acid in the body interferes with normal development in people with sialuria.

Genetic Testing Information

• Genetic Testing Registry: Sialuria

Genetic and Rare Diseases Information Center

• Sialuria

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Clinical Trials

• ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

• SIALURIA

Scientific Articles on PubMed

• PubMed

• Enns GM, Seppala R, Musci TJ, Weisiger K, Ferrell LD, Wenger DA, Gahl WA, Packman S. Clinical course and biochemistry of sialuria. J Inherit Metab Dis. 2001 Jun;24(3):328-36. doi: 10.1023/a:1010588115479. Citation on PubMed
• Leroy JG, Seppala R, Huizing M, Dacremont G, De Simpel H, Van Coster RN, Orvisky E, Krasnewich DM, Gahl WA. Dominant inheritance of sialuria, an inborn error of feedback inhibition. Am J Hum Genet. 2001 Jun;68(6):1419-27. doi: 10.1086/320598. Epub 2001 Apr 18. Citation on PubMed or Free article on PubMed Central
• Leroy JG. Sialuria - RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 2004 Jan 14 [updated 2012 Oct 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from http://www.ncbi.nlm.nih.gov/books/NBK1164/ Citation on PubMed
• Seppala R, Lehto VP, Gahl WA. Mutations in the human UDP-N-acetylglucosamine 2-epimerase gene define the disease sialuria and the allosteric site of the enzyme. Am J Hum Genet. 1999 Jun;64(6):1563-9. doi: 10.1086/302411. Citation on PubMed or Free article on PubMed Central
• Strehle EM. Sialic acid storage disease and related disorders. Genet Test. 2003 Summer;7(2):113-21. doi: 10.1089/109065703322146795. Citation on PubMed