Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism

Background The creatine/creatine-phosphate system is essential for the storage and transmission of phosphate-bound energy in muscle and brain. In infants, inefficiency or failure of this metabolic pathway can impair the development of motor control and mentation. Methods We studied and treated an infant with extrapyramidal signs who was shown-by assay for urinary creatinine and by analysis of brain metabolites with use of nuclear magnetic resonance spectra-to have depletion of body and brain creatine, due to inborn deficiency of guanidinoacetate methyltransferase (GAMT). Findings Long-term oral administration of creatine-monohydrate (4-8 g per day) to this index patient resulted in substantial clinical improvement, disappearance of magnetic resonance (MRI) signal abnormalities in the globus pallidus, and normalisation of slow background activity on the electroencephalogram (EEG). During the 25-month treatment period, both brain and total body creatine concentrations became normal. Interpretation Oral creatine replacement has proved to be effective in one child with an inborn error of GAMT. It may well be effective in the treatment of other disorders of creatine synthesis.