GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY - A NEWLY RECOGNIZED INBORN ERROR OF CREATINE BIOSYNTHESIS

In an infant with progressive, severe extrapyramidal movement disorder and extremely low urinary creatinine excretion, in vivo proton magnet ic resonance spectroscopy of the brain showed a depletion of creatine and an accumulation of guanidinoacetate, the immediate precursor of cr eatine. The suggested defect in creatine biosynthesis at the level of guanidinoacetate methyltransferase was confirmed by the demonstration of defective activity of this enzyme in liver tissue and by identifica tion of the underlying genetic defect. Creatine substitution by means of oral creatine monohydrate at high dosage (4-8 g per day) resulted i n a striking improvement of the extrapyramidal movement disorder, norm alisation of abnormal slow background activity in the EEG, and disappe arance of bilateral abnormal signal intensities in the globus pallidus . The low urinary creatine excretion normalized and brain creatine and creatine phosphate, as measured by in vivo magnetic resonance spectro scopy, increased significantly. Guanidinoacetate methyltransferase def iciency is a new, treatable inborn error of metabolism. Screening meth ods and non-invasive diagnosis of the enzyme defect are needed for the early detection and treatment of patients with this effect.