Guanidinoacetate methyltransferase deficiency
Guanidinoacetate methyltransferase deficiency (GAMT deficiency) is an autosomal recessive cerebral creatine deficiency that primarily affects the nervous system and muscles. It is the first described disorder of creatine metabolism, and results from deficient activity of guanidinoacetate methyltransferase, an enzyme involved in the synthesis of creatine. Clinically, affected individuals often present with hypotonia, seizures and developmental delay. Diagnosis can be suspected on clinical findings, and confirmed by specific biochemical tests, brain magnetic resonance spectroscopy, or genetic testing. Biallelic pathogenic variants in GAMT are the underlying cause of the disorder. After GAMT deficiency is diagnosed, it can be treated by dietary adjustments, including supplementation with creatine. Treatment is highly effective if started early in life. If treatment is started late, it cannot reverse brain damage which has already taken place. Signs and symptoms Individuals with GAMT deficiency appear normal at birth. Shortly after birth, infants may start to show signs, as the consequences of decreased creatine levels in their body become more apparent. These clinical findings are relatively non-specific, and do not immediately suggest a disorder of creatine metabolism. Common clinical findings, as with other cerebral creatine deficiencies, include developmental delay (both intellectual and motor), seizures and hypotonia. Speech delay, autism, and