Aspartylglucosaminuria

Definition

Definition of Aspartylglucosaminuria
Aspartylglucosaminuria (AGU), also called aspartylglycosaminuria, is a rare, autosomal recessive lysosomal storage disorder caused by deficient activity of the enzyme N-aspartyl-beta-glucosaminidase (aspartylglucosaminidase). This enzyme normally cleaves long sugar chains known as oligosaccharides in the lysosome. When N-aspartyl-beta-glucosaminidase is deficient these long sugar chains build up and eventually lead to the clinical features of AGU. AGU is one of seven identified Glycoprotein Storage Diseases.

Symptoms

Symptoms of Aspartylglucosaminuria
Children often show no symptoms at birth. During the first year of life inguinal (groin) and umbilical hernias are common. Enlargement of the liver and spleen may occur, neither of which usually gives rise to serious symptoms. Some children also suffer from diarrhoea.

During early childhood recurrent infections of the ear and upper respiratory system are common.

Initially, motor development is normal. The first signs of impaired development usually manifest in the child’s early years. The child is physically uncoordinated and speech and language development are delayed. Coordination remains poor, but with support and help most individuals can manage everyday activities and participate in play and sporting activities until they reach adulthood.

One characteristic of the disease is a progressive slowing of intellectual development. During their first years children develop normally, but before school age concentration problems, as well as delayed language and intellectual development, become apparent. Development continues, but is slower than normal. Young people in their mid-teens are at their intellectual peak, at which time they can be assessed as having mild to moderate intellectual disabilities. After this age teenagers either remain at this developmental stage or deteriorate slightly until they are between 25 and 30 years of age. After this age learned skills are lost at an increasing rate, resulting in severe learning disability. At the same time, motor skills deteriorate. People with the disease become successively less mobile and more dependant on help and support from those around them. Eventually they will need a wheelchair. However, it should be remembered that there are wide variations both in individuals’ levels of intellectual development and in the progression of the disease.

Causes

Causes of Aspartylglucosaminuria
Lysosomes are small units found in all the cells of the body except red blood cells. With the help of enzymes (a sort of protein) the role of lysosomes is to interact with, and break down, different substances. In this process the constituent parts of the materials are released and become available for re-use. In this way proteins, for example, are broken down into amino acids. These newly-released “building blocks” are then transported out of the lysosomes and become available to cells for the production of new substances.

Aspartylglucosaminidase normally breaks down proteins which contain carbohydrates (glycoproteins). These are plentiful in the tissues of the body, particularly in the cells and cell surfaces of the liver, spleen, thyroid and nerves. When glycoproteins cannot be broken down in the usual way, residues of aspartylglycosaminase and certain other substances accumulate in the lysosomes. These residues cause progressive damage to tissues and organs, manifesting in symptoms of aspartylglucosaminuria.

Diagnosis

Diagnosis of Aspartylglucosaminuria
Clinical manifestations consist of psychomotor retardation, grotesque facial appearance, hepatosplenomegaly, ventral hernia and skeletal abnormalities. It is a member of Finnish disease heritage, a group of diseases or syndromes caused by mutation in a single gene characterized by higher frequency in Finland than the rest of the world.

Treatment

Treatment of Aspartylglucosaminuria
There is no cure for AGU. Treatment is limited to reducing or controlling symptoms. For example, medication may control seizures. It is encouraged that individuals with AGU routinely see their genetic counselors, neurological, ophthalmological, and other specialists as symptoms arise, to maintain the control of their effects.

Prognosis

Prognosis of Aspartylglucosaminuria
Consult with your doctor.

Prevention

Prevention of Aspartylglucosaminuria
Consult with your doctor.