Arginine:glycine amidinotransferase deficiency
Arginine:glycine amidinotransferase deficiency is an inherited metabolic disorder that impairs the body's ability to produce creatine, primarily affecting brain function and development.
Overview
Arginine:glycine amidinotransferase deficiency is an inherited disorder that primarily affects the brain. Individuals with this condition often experience mild to moderate intellectual disability and delayed speech development. Some may exhibit autistic behaviors that impact communication and social interaction. Seizures, particularly triggered by fever, are also a common feature.
Symptoms
- Mild to moderate intellectual disability
- Delayed speech development
- Autistic behaviors affecting communication and social interaction
- Seizures (especially during fevers)
- Failure to thrive (inability to gain weight or grow at the expected rate)
- Delayed development of motor skills, such as sitting and walking
- Weak muscle tone
- Tendency to tire easily
Causes
The disorder is caused by mutations in the GATM gene, which provides instructions for making the enzyme arginine:glycine amidinotransferase. This enzyme is responsible for the first step in the synthesis of creatine, a compound essential for the body to store and use energy properly.
Mutations in the GATM gene impair the enzyme's ability to participate in creatine synthesis, leading to a shortage of creatine. The impact of this deficiency is most severe in organs and tissues with high energy demands, particularly the brain.
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have mutations. Parents of an affected individual typically each carry one copy of the mutated gene but do not show signs or symptoms of the condition.