Prenatal Diagnosis of Guanidinoacetate Methyltransferase Deficiency: Increased Guanidinoacetate Concentrations in Amniotic Fluid

Abstract

Guanidinoacetate methyltransferase (GAMT; EC 2.1.1.2) deficiency (OMIM 601240) is an autosomal recessive disorder of creatine biosynthesis, characterized clinically by mental retardation, language delay, extrapyramidal movements, epilepsy, and autistic behavior (1). Biochemically, GAMT deficiency is characterized by depletion of creatine and accumulation of guanidinoacetate (GAA) in the brain and body fluids (2). Treatment by creatine supplementation (combined with arginine restriction and ornithine supplementation) partially restores (∼70%) cerebral creatine, reduces seizures, and improves behavior, but it does not reverse the mental retardation (3). We have described a method to measure GAA and creatine in plasma and urine by liquid chromatography–tandem mass spectrometry (LC-MS/MS) (4). In the present study, we validated this method for measurement of GAA and creatine in amniotic fluid, and we report the first GAMT prenatal diagnosis based on a combination of molecular and biochemical investigations. We …