Arginine:glycine amidinotransferase deficiency
Arginine:glycine amidinotransferase (AGAT) deficiency is a rare inherited brain and muscle disorder. It happens when both copies of the GATM gene are faulty, so the body doesn’t make enough of the enzyme arginine:glycine amidinotransferase. This enzyme normally starts creatine production, which is important for giving energy to brain and muscle cells. Without enough creatine, people may have intellectual disability, muscle weakness, and sometimes seizures.
What causes it
- Inheritance: autosomal recessive (you must inherit one faulty gene from each parent).
- The GATM gene provides the enzyme needed to begin creatine biosynthesis in the kidney and pancreas.
- The lack of creatine mainly affects the brain and muscles.
How it presents and how it’s diagnosed
- Symptoms: intellectual disability, muscle weakness, and sometimes seizures.
- Blood and urine tests: show low creatine and low guanidinoacetate.
- Brain imaging with magnetic resonance spectroscopy (MRS): shows absence of creatine in the brain.
- Diagnosis is supported by genetic testing showing two faulty copies of GATM. If results are unclear, enzyme tests or measuring creatine uptake in fibroblasts may help.
- Prenatal testing is possible if the family variants are known.
How it’s treated
- The main treatment is oral creatine supplementation to restore creatine levels in the brain and muscles.
- Early treatment (as soon as possible) gives the best outcomes. It cannot reverse existing intellectual disability but often improves muscle strength.
- If an asymptomatic sibling starts treatment early, they may have better outcomes than an untreated child.
- Ongoing treatment is needed for life because creatine is quickly converted to creatinine.
- Monitoring includes checking creatine levels in blood and urine, and brain creatine levels by MRS.
How rare it is
- AGAT deficiency is very rare, with fewer than 20 reported cases worldwide.
- It was first described in 2000 in two sisters aged 4 and 6.
This page was last edited on 2 February 2026, at 14:42 (CET).