What is Aspartylglucosaminuria?
Aspartylglucosaminuria (AGU) is one of seven identified Glycoprotein storage diseases. These inherited diseases are part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many different oligosaccharides (long sugar chains.) These sugar chains are continuously made and broken down in our bodies, and this process is necessary for appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the sugar chains. When an enzyme is not working, it leads to the build up of the sugar chains in the lysosome. This build up is gradual and eventually leads to the clinical features of AGU. Features may progress in severity over time.
In AGU, the specific enzyme that is absent is called aspartylglucosaminidase.
What are the clinical features of Aspartylglucosaminuria?
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.
How is Aspartylglucosaminuria inherited?
AGU is not contagious and cannot be "caught". It is a genetic condition, which means that it is caused by a change in the instructions that direct the way our bodies grow and develop. These instructions are called genes. People have two copies of all their genes, including the gene for AGU (aspartylglucosaminidase.) One copy is inherited from the mother in the egg, and one from the father in the sperm. For a person to have AGU, they must inherit changes in both of their AGU genes resulting in instructions that do not function properly. This is known as autosomal recessive inheritance. For a couple to have a child with AGU, both parents must have at least one changed copy of the AGU gene which they both pass on to their child. Parents do not have control over which genes they pass on to their children. If a person has one changed copy of the AGU gene and one normal copy of the AGU gene they are said to be a carrier of the condition and will not show any symptoms of AGU. If two parents are both carriers, they have a 1 in 4 (25%) chance of having a child with AGU in each pregnancy.
What testing is available to determine if my child or I have Aspartylglucosaminuria?
Testing for Glycoprotein storage diseases is typically performed in conjunction with a genetics evaluation. A genetics team takes into account the medical history and clinical features of a patient to determine what type of genetic testing is appropriate. For the diagnosis of an Oligosaccharide storage disease, a urine test should show increased oligosaccharides. To determine if the patient has AGU, the urine test should be followed by a blood test or skin biopsy. The blood or skin sample should show decreased activity of the enzyme aspartylglucosaminidase.
For families who have had a child diagnosed with AGU, prenatal diagnosis is available in future pregnancies by looking at aspartylglucosaminidase activity through Chorionic Villus Sampling (CVS) or amniocentesis. Prenatal diagnosis by detection of AGU gene changes is also available for families in which the responsible gene changes have been identified. What type of treatment is available for Aspartylglucosaminuria? Individuals with AGU should have routine follow-up with Genetics, as well as Neurology, Pulmonary and ENT as indicated. Currently, there is no cure to stop the progression of symptoms of AGU and treatment is aimed at addressing the individual problems as they arise.