Aspartylglucosaminuria (AGU) leads to a deficiency of the aspartylglucosaminidase enzyme. This deficiency hinders the breakdown of glycoasparagines, resulting in their accumulation in the body’s fluids and tissues.
AGU is a progressive disorder, with affected individuals typically appearing normal at birth, but later experiencing developmental delays, attention problems, and restlessness. Speech delays are often the first noticeable symptom, occurring around the age of two or three, followed by speech difficulties, slow learning, and coordination issues. Over time, intellectual disability worsens, leading to a loss of skills and abilities. In adulthood, profound intellectual impairment and a loss of speech become evident, along with the possibility of epileptic seizures and the need for a wheelchair. Physical characteristics of AGU include widely spaced eyes, a broad nose and face, full lips, and small ears, which tend to coarsen with time. Connective tissue problems and osteoporosis may develop, along with spinal and skeletal deformities. While children with AGU may be taller than their peers, affected adults often have short stature due to the lack of a growth spurt during puberty. Additionally, individuals with AGU are more prone to frequent skin and respiratory infections.
AGU is caused by pathogenic (disease-causing) variants in the AGA gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition.
Other names for this condition are AGA deficiency, aspartylglucosamidase deficiency, aspartylglucosaminidase deficiency, and glycosylasparaginase deficiency.
Resources:
National Organization for Rare Disorders
Revised July 2023
