Guanidinoacetate methyltransferase (GAMT) deficiency

Keywords Disease name and synonyms Excluded diseases Diagnostic criteria / definition Prevalence Clinical description Management including treatment Etiology Diagnostic methods Genetic counseling / Prenatal diagnosis Unresolved Problems References Abstract Guanidinoacetate methyltransferase (GAMT, EC 2.1.1.2) deficiency is a newly recognized inborn error of creatine synthesis. The clinical phenotype is variable including a spectrum of neurological involvement from progressive extrapyramidal movement disorder and severe muscular hypotonia, to epilepsy and mental retardation. Biochemical findings include high urinary excretion of guanidinoacetate (immediate precursor of creatine and substrate to the deficient enzyme activity), low urinary excretion of creatinine, and depletion of creatine in brain and muscle. Enzymatic diagnosis is possible by the demonstration of deficient GAMT activity in liver, skin fibroblasts and virus transformed lymphoblasts. Prenatal diagnosis has not been performed so far. Symptoms are partly reversible under oral supplementation of creatine-monohydrate. GAMT deficiency is an autosomal recessive inherited disorder. In the 9 patients known so far in the literature, 5 mutant alleles have been identified which are located in exon 2 and exon and intron 6 of the GAMT gene. The most efficient way for investigation of patients at risk seems to be determination of guanidinoacetate in body fluids. Several analytical methods including gas chromatography/mass spectrometry, tandem mass spectrometry and column chromatography are available for this purpose.