Aspartylglycosaminuria

Aspartylglycosaminuria is a very rare lysosomal storage disease that causes a progressive decline in mental functioning. Infants with aspartylglycosaminuria appear healthy at birth with signs and symptoms beginning around the age of 2 or 3. Major symptoms may include coarse facial features, spine and eye deformities, behavior problems, and intellectual disability.  Symptoms result from a deficiency in an enzyme called aspartylglycosaminidase, which leads to an accumulation of a protein called glycoasparagine in the body tissues and  increased excretion of this protein in the urine. Aspartylglycosaminuria is inherited in an autosomal recessive fashion and caused by mutations in the AGA gene. It is commonly seen in individuals of Finnish decent.^[1][2][3]

Infants with aspartylglycosaminuria appear healthy at birth, and development is typcailly normal throughout childhood. The first sign of this condition, which becomes evident around the age of 2 or 3, is usually delayed speech. Mild intellectual disability then becomes apparent, and learning occurs at a slowed pace. Intellectual disability progressively worsens in adolescence. Most people with this disorder lose much of the speech they have learned, and affected adults usually have only a few words in their vocabulary. Adults with aspartylglucosaminuria may develop seizures or problems with movement.^[3]

People with this condition may also have bones that become progressively weak and prone to fracture (osteoporosis), an unusually large range of joint movement (hypermobility), and loose skin. Affected individuals tend to have a characteristic facial appearance that includes widely spaced eyes (ocular hypertelorism), small ears, and full lips. The nose is short and broad and the face is usually square-shaped. Children with this condition may be tall for their age, but lack of a growth spurt in puberty typically causes adults to be short. Affected children also tend to have frequent upper respiratory infections. Individuals with aspartylglucosaminuria usually survive into mid-adulthood.^[3] The skeleton may also become deformed. The spine may be twisted (scoliosis) and the neck may be unusually short. The eyes may also develop cataracts. Behavior problems are common. Lung, heart and blood problems tend to occur in later years.^[2]

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.^[3]

You you can view our Organizations page for this condition to find advocacy organizations that provide information and supportive resources. They may be able to assist you in connecting with other families with aspartylglycosaminuria.