Aminoacylase 1 deficiency
Aminoacylase 1 deficiency is an inherited metabolic disorder characterized by the presence of N-acetylated amino acids in the urine and potential neurological complications.
Overview
Aminoacylase 1 deficiency is an inherited disorder that can cause neurological problems. The pattern and severity of signs and symptoms vary widely among affected individuals. While some people with the condition have no related health problems, others experience developmental challenges.
Symptoms
Common signs and symptoms associated with this condition include:
- Delayed development of mental and motor skills (psychomotor delay)
- Movement problems
- Reduced muscle tone (hypotonia)
- Mild intellectual disability
- Seizures
A key feature common to all people with aminoacylase 1 deficiency is high levels of modified protein building blocks, called N-acetylated amino acids, in the urine.
Causes
Aminoacylase 1 deficiency is caused by mutations in the ACY1 gene. This gene provides instructions for making the enzyme aminoacylase 1, which is involved in the breakdown of proteins. Many proteins have an acetyl group attached to one end—a modification called N-acetylation—which helps protect and stabilize the protein. Aminoacylase 1 performs the final step in the breakdown of these proteins by removing the acetyl group so the amino acids can be recycled.
Mutations in the ACY1 gene lead to an enzyme with little or no function. Consequently, acetyl groups are not efficiently removed from a subset of amino acids, and the excess N-acetylated amino acids are released in the urine. It is currently unknown how this reduction in enzyme function leads to the observed neurological problems.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning 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 typically do not show signs or symptoms of the condition.