Summary

Aspartylglycosaminuria (AGU) is an autosomal recessive lysosomal storage disease belonging to the oligosaccharidosis group (also called glycoproteinosis), that is only exceptionally found outside of Finland. It is due to deficiency in N-aspartylglycosaminidase, an enzyme that cleaves N-acetylglycosamine-asparagine bond found into many glycopeptides and N-glycosyled proteins, and causes excess accumulation of glycoasparagine in the body tissues and its increased excretion in urine. Transmission is autosomal recessive. Clinical signs include slowly developping mental retardation, beginning with clumsiness, late speech, and hyperkinesia, mild facial dysmorphism, and slight kyphoscoliosis. Hepatosplenomegaly is rare and has only been reported in non-Finnish cases. Biochemically it is characterized by increased urinary excretion of aspartylglycosamine on an aminoacid or oligosaccharide chromatography. Results are confirmed by the low activity of aspartylglycosaminidase measured in lymphocytes, fibroblasts, amniocytes or the trophoblast. The gene has been located (on 14q32-q33). In Finland, two major mutations have been evidenced (AGUfin major and AGUfin minor) that account for 98% of diseased alleles, and systematic screening for heterozygous individuals has thus been made possible. Elsewhere, mutations are very heterogenous. The only attempt of curative treatment to this day is allogenic bone marrow grafting, but the results in 5 Finnish patients were limited.

Expert reviewer(s)

• Dr Roseline FROISSART
• Dr Irène MAIRE