Aspartylglucosaminuria
Aspartylglucosaminuria is a rare, progressive genetic condition that primarily affects mental functioning and movement, worsening from early childhood into adulthood.
Overview
Aspartylglucosaminuria is a condition that primarily affects mental functioning and movement. This condition worsens over time. Infants with aspartylglucosaminuria appear healthy at birth, and development is typically normal throughout early childhood.
Symptoms
Signs and symptoms of aspartylglucosaminuria develop and change as an individual ages:
Early Childhood
- Delayed speech and mild intellectual disability, typically beginning around age 2 or 3
- Problems coordinating movements
- Frequent respiratory infections
- Hernias, which are protrusions of organs through gaps in muscles
- A growth spurt resulting in a large head size (macrocephaly)
- Children may be tall for their age
Adolescence and Adulthood
- Worsening intellectual disability and movement problems
- Loss of much of the speech learned in childhood, with affected adults usually having only a few words in their vocabulary
- Psychological disorders
- Development of seizures
- Short stature and a small head size (microcephaly) due to a lack of a growth spurt in puberty
Other Physical Features
- Bones that become progressively weak and prone to fracture
- An unusually large range of joint movement (hypermobility)
- Loose skin
- A characteristic facial appearance that includes widely spaced eyes, full lips, and a square-shaped face
- Poor oral health, including infections and gum disease (gingivitis)
Individuals with aspartylglucosaminuria usually survive into mid-adulthood.
Frequency
In Finland, it is estimated that 1 to 3 individuals are born with aspartylglucosaminuria each year. This condition is less common outside of Finland, but the incidence is unknown.
Causes
Variants (also known as mutations) in the AGA gene cause aspartylglucosaminuria. The AGA gene provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complex chains of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins).
AGA gene variants result in a lack (deficiency) of the aspartylglucosaminidase enzyme in lysosomes, preventing the normal breakdown of glycoproteins. As a result, glycoproteins can build up within the lysosomes. Excess glycoproteins disrupt the normal functions of the cell and can result in cell death. A buildup of glycoproteins seems to particularly affect nerve cells in the brain; loss of these cells causes many of the signs and symptoms of aspartylglucosaminuria.
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- AGA deficiency
- Aspartylglucosamidase deficiency
- Aspartylglucosaminidase deficiency
- Aspartylglycosaminuria
- Glycosylasparaginase deficiency