What Is Aspartylglucosaminuria?

Aspartylglucosaminuria (AGU) is an inherited condition caused by mutations in the AGA gene in which the body lacks an enzyme called aspartylglucosaminidase. A deficiency of the aspartylglucosaminidase enzyme impairs the body's ability to break down large molecules called glycoasparagines, resulting in their buildup in the fluid and tissues of the body.

AGU is progressive, with affected individuals typically appearing normal at birth. Subsequently, children with AGU experience developmental delays and are often characterized as having attention problems and restlessness. Speech delays are often the first symptom recognized, usually around the age of two or three. Speech difficulties, slow learning, and lack of coordination are typical. With time, intellectual disability worsens and some skills and abilities may be lost. Affected adults exhibit profound intellectual impairment and eventually lose the ability to speak. Adolescents and adults with the condition may also experience epileptic seizures and may have the need for a wheelchair later in life.

Individuals with AGU share certain physical features, including widely spaced eyes, a broad nose and face, full lips, and small ears. Their facial features tend to coarsen over time, and connective tissue problems or weakened bones (osteoporosis) may develop. Individuals may also have spinal and skeletal deformities such as a curvature of the spine. While children with AGU tend to be taller than their peers, affected adults often have short stature due to the lack of a growth spurt during puberty. Affected individuals also tend to have more-frequent infections of the skin and respiratory system.

How Common Is Aspartylglucosaminuria?

The prevalence of AGU in the general population is unknown. The condition is most common in individuals of Finnish decent. The prevalence of AGU in Finland is 1.7 in 100,000 to 5 in 100,000 live births.

How Is Aspartylglucosaminuria Treated?

Currently, there is no cure for AGU. Medical professionals can only treat symptoms as they arise. These treatments may include, but are not limited to, special education, anti-seizure medication, and orthopedic aids to help in movement.

What Is the Prognosis for an Individual with Aspartylglucosaminuria?

Individuals with AGU experience a progressive decline in abilities, with most affected adults having profound intellectual impairment and loss of speech. Lifespan is decreased, with death typically occurring between 35 and 50 years of age. The most-common cause of death is severe respiratory infection.