Aspartylglucosaminuria

Aspartylglucosaminuria (AGU) is caused by deficiency of the enzyme N-aspartyl-beta-glucosaminidase.

This enzyme normally degrades long sugar chains known as oligosaccharides in the lysosome. When N-aspartyl-beta-glucosaminidase is deficient, as it is in AGU, these long sugar chains build up and eventually lead to the clinical features of AGU.

Individuals with AGU typically have normal development in infancy. Around the age of 2–4 years, they begin showing signs of developmental delay, but development is still progressing. Initial symptoms may present as clumsiness and/or speech delay. Individuals with AGU also show increased upper respiratory infections. Development continues until about puberty, however, individuals at 13–16 years of age typically show mental and motor development similar to a 5–6 year old. Around puberty, a gradual decline in mental abilities and motor skills occurs. This progressive decline continues until about 25–28 years of age, when rapid impairment of abilities occurs, resulting in severe mental retardation.

Other features of AGU include worsening of connective tissue-related problems as the individual ages. Facial features may coarsen, vertebral and long bone changes may be seen on x-ray, and osteoporosis may occur in adults with AGU. Some patients experience seizures. On MRI, there may be poor differentiation between the gray and white matter, as well as evidence of delayed myelination. Myelin is the covering of nerves that helps with accurate and timely nerve response to stimuli.