Which are the causes of Aspartylglycosaminuria?

Aspartylglycosaminuria is a rare genetic disorder that affects the metabolism of certain sugars and proteins in the body. It is caused by mutations in the AGA gene, which provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is responsible for breaking down a substance called aspartylglucosamine, which is a byproduct of protein metabolism.

The primary cause of Aspartylglycosaminuria is a mutation in the AGA gene. This mutation leads to a deficiency or complete absence of the aspartylglucosaminidase enzyme, resulting in the accumulation of aspartylglucosamine in the body. Over time, this buildup can lead to various symptoms and complications associated with the disorder.

Aspartylglycosaminuria is an autosomal recessive disorder. This means that an individual must inherit two copies of the mutated AGA gene, one from each parent, to develop the condition. If a person inherits only one mutated gene, they are considered carriers and do not typically experience symptoms of the disorder.

The AGA gene mutation affects the lysosomes in cells. Lysosomes are specialized compartments within cells that contain enzymes responsible for breaking down various substances. In individuals with Aspartylglycosaminuria, the lack of functional aspartylglucosaminidase enzyme impairs the lysosomal function, leading to the accumulation of aspartylglucosamine and other substances.

Aspartylglycosaminuria is a progressive disorder. The accumulation of aspartylglucosamine and other substances in the body can cause damage to various tissues and organs over time. This can result in a wide range of symptoms, including intellectual disability, developmental delays, skeletal abnormalities, joint stiffness, coarse facial features, and speech difficulties.

While the exact mechanisms are not fully understood, the buildup of aspartylglucosamine is thought to disrupt normal cellular processes and contribute to the symptoms of Aspartylglycosaminuria. The specific effects of this accumulation on different tissues and organs are still being studied.

Overall, Aspartylglycosaminuria is caused by mutations in the AGA gene, leading to a deficiency of the aspartylglucosaminidase enzyme and subsequent accumulation of aspartylglucosamine in the body. This accumulation disrupts normal cellular processes and contributes to the symptoms and complications associated with the disorder.