Shortly after birth, infants may start to show signs, as the consequences of decreased creatine levels in their body become more apparent.

The most consistent clinical manifestation is developmental delay or intellectual disability, which is observed in all affected individuals, and can range from mild to severe.

[4] Additional symptoms include movement disorders, such as chorea, athetosis, dystonia or ataxia, observed in about 30% of GAMT patients.

[10] This gene codes for the enzyme guanidinoacetate methyltransferase (GAMT), which participates in the two-step synthesis of the compound creatine from amino acids glycine, arginine and methionine.

[8] The effects of GAMT deficiency are most severe in organs and tissues that require large amounts of energy, such as the brain and muscles.

The initial diagnosis is typically established via measurement of creatine, creatinine, and guanidinoacetate in plasma, cerebrospinal fluid, or dried blood spots.

[5] Brain magnetic resonance spectroscopy can also be used in diagnosis, and will show decreased levels of creatine in affected individuals.

[5] Newborn screening assays measure the amount of guanidinoacetate in a dried blood spot using tandem mass spectrometry.

[16] In 2022, a federal advisory committee voted to include GAMT in the Recommended Universal Screening Panel starting in January 2023.

Around the world, the state of Victoria, Australia began screening for GAMT in 2004,[17] leading to the diagnosis of a newborn at birth in 2022.

[8] Prior to the addition of GAMT deficiency to newborn screening panels, younger siblings of affected individuals may have been tested at birth and treated early.