Aspartylglucosaminuria

Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder caused by deficiency of the enzyme aspartylglucosaminidase (AGA), which is responsible for breaking down glycoproteins. The condition is caused by pathogenic variants in the AGA gene located on chromosome 4q34.3. Without functional AGA enzyme, aspartylglucosamine and other glycoasparagines accumulate in tissues and are excreted in excess in the urine, leading to progressive cellular damage. AGU is particularly prevalent in the Finnish population, where it is one of the most common lysosomal storage diseases, though cases have been reported worldwide. The disease primarily affects the central nervous system, skeletal system, and connective tissues. Infants may appear normal at birth, though some may present with neonatal respiratory infections or hernias. During early childhood, developmental delay becomes apparent, with speech delay often being one of the first recognized signs. Progressive intellectual disability is a hallmark feature, with cognitive abilities typically plateauing in adolescence and then declining in adulthood. Affected individuals commonly develop coarse facial features, short stature, joint laxity, and skeletal abnormalities. Recurrent infections, diarrhea, and behavioral issues including hyperactivity and sleep disturbances are also frequently observed. Many patients develop seizures in adulthood. There is currently no approved curative treatment for aspartylglucosaminuria. Management is primarily supportive and symptomatic, including speech therapy, physical therapy, educational support, and management of behavioral symptoms. Bone marrow transplantation has been attempted in some patients with variable results, showing potential benefit when performed early in the disease course, though outcomes have been inconsistent. Enzyme replacement therapy and gene therapy approaches are areas of active research. Life expectancy is reduced, with many patients surviving into their fourth or fifth decade of life.

Common questions about Aspartylglucosaminuria